Synthesis of alkyl sulfoniums from alkenes via alkenyl sulfonium intermediates and their application in the synthesis of Anti-markovnikov type addition products

Abstract

As terminal alkenes, so-called alpha-olefines, are easily available and relatively cheap starting materials, their selective transformations are one of the fundamental reactions in organic chemistry which are used in many large-scale chemical processes and academic laboratories. Markovnikov-type alkene reactivity encompasses a significant portion of chemical reaction space for unsaturated hydrocarbons and offers a direct method for synthesizing fundamental commodities and fine chemicals. Equally important is the availability of complementary anti-Markovnikov type addition products. However, this objective has proven to be a challenging task for organic chemists. The recently discovered chemistry of alkenyl-sulphonium salts creates a new opportunity in forming anti- Markovnikov type addition products.

Description

[0001] P140257-2417-LG SYNTHESIS OF ALKYL SULFONIUMS FROM ALKENES VIA ALKENYL SULFONIUM INTERMEDIATES AND THEIR APPLICATION IN THE SYNTHESIS OF ANTI-MARKOVNIKOV TYPE ADDITION PRODUCTS Field of the invention The present invention(s) relates to a method for the preparation and further transformation of alkyl sulfonium salts wherein said method comprises the following steps: i) an alkene is reacted to obtain an alkenyl sulfonium salt or synthetic equivalent; ii) the obtained sulfonium salt is reduced with a reductant to form an alkyl sulfonium salt; iii) optionally, the alkyl sulfonium salt is separated and purified or directly transformed using a nucleophile into an addition product preferably with an anti-Markovnikov type selectivity. Background of the invention Alkylating agents, such as alkyl halides and alkyl pseudohalides, are valuable and fundamental intermediates in the synthesis of agrochemicals and pharmaceuticals. However, their handling, selective transformations, removal of their trace impurities, and cost-efficient preparation can often be cumbersome. On the other hand, alkyl-sulfonium salts offer promising alternatives as potential intermediates for substitution reactions due to their advantageous properties, such as ease of handling (non-volatile) and enhanced reactivity as electrophiles in various transformations beyond classical ones. These state-of-the-art transformations include cross-couplings (ref 1), photoredox transformations (ref 2), substitution reactions (ref 3), and others (ref 4). So far, the synthesis of alkyl-sulfonium salts has relied on their formation from pre-existing oxidized compounds, such as other alkylating agents (e.g., bromides or triflates, ref 5), or through the use of organometallic reagents (e.g., Grignard reagents, ref 6). Importantly, their practical and cost-effective synthesis on an industrial scale remains a challenge. As terminal alkenes, so-called alpha-olefines, are easily available and relatively cheap starting materials, their selective transformations are one of the fundamental reactions in organic chemistry which are used in many large-scale chemical processes and academic laboratories. Nonetheless, transforming olefins into alkyl sulfonium salts has been mostly limited to lengthy and non-practical routes (e.g., a sequence of hydroboration- oxidation- triflation-substitution) which limits the widespread use of these methodologies. A fundamentally different approach would be the transformation of terminal alkenes to alkyl sulfonium salts using alkenyl sulfonium salts as intermediates, which process involves a site-selective C-H oxidation (i.e., alkene into alkenyl-sulfonium) and a reduction step (i.e., alkenyl sulfonium into alkyl sulfonium). However, there is no precedent for such transformation of unbiased alpha-olefins (non-activated, no directing group; e.g., fatty olefin derivatives). While the C-H oxidative transformation of an alkene into alkenyl-thianthrenium salts transformation is known in the art (ref 7), there is still room for further improvement regarding cost and scalability. State-of-art solutions for thianthrenation include the use of sulfoxides (i.e., thianthrenium-S-oxide (TTO)) combined with expensive activating agents (e.g., trifluoroacetic anhydride combined with triflic acid, ref 8) or the use of electrochemical activation (requiring split electrochemical cells and expensive electrolyte salts, ref 9). On the other hand, such activations which utilize direct chemical oxidants in thianthrenation (i.e., dimesyl peroxide and Selectfluor) are limited to the transformation of a small number of different class of compounds, e.g., electron- rich arenes. (ref 10) Thus, there is no precedent for the direct oxidative transformation of alkenes into alkenyl- thianthrenium salts using thianthrene (TT) and an appropriate chemical oxidant. Regarding the subsequent reductive transformation, there is also no precedent for the selective, partial reduction of alkenyl sulfoniums into alkyl sulfoniums. This may be because there are many synthetic challenges to overcome: i) alkenyl-thianthrenium salts display multiple and distinct reactivities with nucleophiles (see below), to control the various competing synthetic paths is not straightforward, ii) there is also a challenge to control the selectivity of the alkenyl thianthrenium salt reductions and prohibit overreduction of the product (i.e., alkyl sulfonium into alkane). Analogous problems are well known in case of the selective reduction of conventional alkenyl halides and pseudohalides. (ref 11) The recently discovered chemistry of alkenyl-sulphonium salts creates a new opportunity in olefin chemistry. (Ref 12) This activation approach relies on the synthesis of covalent sulfonium species, which highly reactive molecules are converted into more valuable compounds with or without their isolation. As seminal works illuminated the possibility of producing and transforming these species, their narrow scope limited the utility of this unique and orthogonal activation mode. (Ref 13) The introduction of thianthrene into this chemistry by Ritter’s group, however, enabled the synthesis of alkenyl thianthrenium salts from a broad range of olefins in a stereo- and regioselective manner and these salts were further transformed via cross-coupling reactions. (Ref 14) As outlined in Chen’s doctoral dissertation, (Ref 15) these alkenyl thianthrenium species were also found to engage in reactions consisting of direct nucleophilic replacements. These seminal experiences could be explained by three types of thianthrenium reactivity, more specifically: Type I: reaction as a vinyl cation equivalent giving a β-carbon substituted product (e.g., reaction with cyanide); Type II: reaction as a dication equivalent to afford cyclic or disubstituted products (e.g., reaction with primary amines). Type III: reaction as an allylic cation with the double bond shifted (e.g., reaction with carboxylic acids). Then, Wickens demonstrated that dicationic and related metastable bis- thianthrenium adducts are readily generated employing electrochemistry and their reactivities can be directed to converge and provide similar reactivities as above, including the formation of vinyl nitriles (Type I), aziridines, diamines, dihalogenides, cyclopropanes (Type II) or allylic amines (Type III). (Ref 16) At the same time, Shu reported analogous allylic functionalizations via alkenyl thianthrenium salts to attain allylic amination, esterification, etherification, and arylation (Type III) and later cyclopropanation, aziridination (Type II) and cine-substitution (Type I). (Ref 17) Additionally, we reported the synthesis of various α,β-unsaturated carbonyls using amine-oxides and sulfoxides as oxidants (Type III, Ref 18) and a novel formal allylic oxidation reaction (Type IV). Very recently, Wickens introduced an additional, distinct reactivity, namely the heterodifunctionalization (i.e., aminofunctionalization) of alkenyl-thianthrenium salts by using an appropriate N-nucleophile (i.e., phtalimide-potassium) combined with another nucleophile of various kinds (e.g., amines) (Type V). (ref 19) Summarizing the prior knowledge regarding Type V reactivity to date, these non-typical transformations are all enabled by the oxidative activation of olefins via sulfonium species followed by the sequential addition of two preferably different nucleophiles to form heterodifunctionalized products. More specifically, these sulfonium species may consist of alkenyl sulfonium salts, bridged dicationic, and bis-adducts, which can be treated as synthetic equivalents in general terms. These intermediates are obtained from the reaction of olefins and activated sulfonium reagents prepared by either means of chemical activation (e.g., reacting thianthrene S-oxide with trifluoromethanesulfonic anhydride) or electrochemical synthesis (e.g., anodic oxidation of thianthrene). The main challenge of this chemistry lies in controlling the reactivity of these species in the presence of nucleophiles, thus keeping the desired downstream transformation (i.e., Type V) and suppressing other possible reactivities (e.g., Type I). To the best of our knowledge, there are no reports describing the successful reaction of the said alkenyl sulfonium salts or synthetic equivalents with nucleophilic reducing agents (i.e., sodium borohydride) combined with an additional nucleophile (e.g., amine), in particular including the Type V reactivity to furnish anti- Markovnikov type addition products. Similarly, there are no precedents to interrupt such a process after the reduction step and selectively form alkyl sulfonium salts. Markovnikov-type alkene reactivity encompasses a significant portion of chemical reaction space for unsaturated hydrocarbons and offers a direct method for synthesizing fundamental commodities and fine chemicals. Equally important is the availability of complementary anti-Markovnikov type addition products. However, this objective has proven to be a challenging task for organic chemists. In recent decades, synthetic chemists have invested considerable effort into identifying a broadly applicable method for achieving precise control over the regioselectivity of olefin hydrofunctionalization. Current efforts in this field primarily revolve around utilizing transition metal-based catalytic systems, and radical reactions (including photoredox transformations). However, these transition metal catalyst systems, such as those developed by Hartwig (Ref 20), Beller (Ref 21), Grubbs, (Ref 22), Buchwald (Ref 23) have demonstrated limited success in achieving anti- Markovnikov addition of amines and water to alkenes. These successes have been predominantly observed with terminal styrenes and their derivatives. Although transition metal complexes are used in small quantities, their handling and cost-efficient preparation can still be cumbersome. Alternatively, in the realm of photochemistry, the anti-Markovnikov adducts can also be accessed. Nevertheless, these catalytic photosensitized reactions have primarily focused on monosubstituted styrenes or trisubstituted alkenes. Aliphatic alkenes and especially alpha- olefins are rarely represented in these reactions (developed by Mizuno (ref 24), Nicewicz (ref 25), Glorius (ref 26), Arnold (ref 27), Gassman (ref 28), Inoue (ref 29)). For electron-rich olefins, transition-metal-based polypyridyl catalysts have found utility. However, less oxidizable alkenes like styrenes, as well as mono-, di-, and trisubstituted alkenes, possess oxidation potentials outside the range of these catalysts. Some organic photooxidants with high reduction potentials in the excited state have been identified as potential solutions to this problem, although some suffer from short excited-state lifetimes (including the work of Fukuzumi (ref 30), Nicewicz (ref 25), Glorius (ref 26)). Another challenge arises when dealing with less oxidizable olefins, as the choice of a suitable oxidant becomes crucial. Redox agents capable of oxidation often deliver oxygen instead of participating in single electron oxidation, resulting in the oxidation of both the olefin and the reagent during the reaction (e.g., Nicewicz's hydroamination using primary amines, as they undergo oxidation). Selecting an appropriate hydrogen source for the hydrogen atom transfer (HAT) step can also be challenging, as there is no universally suitable option. Ritter presented a photoredox transformation that enables anti-Markovnikov hydrochlorination and hydronitrooxylation of α-olefins. (ref 31) Besides catalytic direct functionalization, various indirect methods have emerged like the hydroalumination / oxidation sequence of Ziegler (ref 32), or the hydroboration / oxidation sequence of Brown and Zweifel (ref 33). Furthermore, to reduce the nonrecyclable waste generation and safety concerns of this venerable reaction, several modern alternative oxidation / reduction methods have emerged, including Grubbs’ (ref 22) and Feringa’s (ref 34) approaches via anti-Wacker products, Arnold’s biocatalytic (ref 35) oxidation methodology, and regioselective epoxide hydrogenation by Gansäuer and Norton (ref 36). While these indirect / formal methodologies are extensively exploited, the need to broaden the applicability of these approaches remains. However, a scalable, metal-free, ionic (not including radical intermediates) methodology that allows for the addition of a variety of heteroatom nucleophiles across a broad range of unactivated alkenes remains elusive. The problem to be solved by the invention The problem to be solved by the present invention is to provide a method for the selective transformation of alkenes to alkyl sulfonium salts, where the use of said methodology has the following features: a) capability to selectively transform unbiased (non-activated, no directing group) alkenes, especially aliphatic alpha-olefines (e.g. fatty olefin derivatives) into alkyl sulfonium salts, b) high regioselectivity in functionalization, preferring the selective formation of an anti-Markovnikov type products, c) capability to further transform the product obtained, preferably without isolation. This includes substitution reactions with various nucleophiles to generate C-H, C-N, C-O, C=O, C-S, C-Halogen, C-C bonds and generally known transformations, especially reactions with deuterium / tritium labelled reductants to form isotope labelled compounds, d) high chemoselectivity upon olefin functionalization, especially tolerating the presence of functional groups such as an ester / carboxylic acid / alcohol / halogen / pseudohalogen group, e) high selectivity over overreduction products f) mild operational conditions g) practical work-up conditions for efficient removal of by- and side-products h) utilization of cost-effective and readily available reagents which are requisite for industrial scale productions. The discovery according to the present invention During our experiments, we found that the above features can be achieved by merging an interrupted Type V electrophilic reactivity (see figure above) of alkenyl sulfonium salts or synthetic equivalents with the nucleophilic reactivity of appropriate reducing reagents (i.e., sodium borohydride). More specifically, a novel methodology has been developed based on this concept, comprising the following steps: i) an alkene was reacted to obtain an alkenyl thianthrenium salt or synthetic equivalent; ii) the obtained thianthrenium salt is reduced with a reductant to form an alkyl thianthrenium salt; iii) optionally, the alkyl thianthrenium salt is separated and purified (interrupted Type V reactivity) or directly transformed using a nucleophile into an addition product with an overall anti-Markovnikov selectivity (non-interrupted Type V reactivity, see figure above). Additionally, a novel method was introduced for the preparation alkenyl sulfonium salts from alkenes well suitable for industrial scale production. More specifically, we were surprised to find that combining thianthrene, 1-Chloromethyl-4-fluoro- 1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) and boron trifluoride diethyl etherate as an additive enables the formation of alkenyl sulfonium salts. Brief description of the invention 1. Provided herein are methods for preparing alkyl sulfonium salts according to Formula I: wherein R1 and R2, independently from each other, are H; C1-C20 alkyl, preferably C1-C14 alkyl; C2-C20 alkenyl, preferably C2-C14 alkenyl; C2-C20 alkynyl, preferably C2-C14 alkynyl; -O-C1-C20 alkyl, preferably - O-C1-C14 alkyl; -O-C2-C20 alkenyl; -O-C2-C20 alkynyl; C3-C10 cycloalkyl; 4-10-membered heterocycloalkyl containing one or more heteroatoms independently selected from N, O and S; C6-C14 aryl, preferably phenyl; or 5-10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S; wherein each alkyl, alkenyl, and alkynyl can be straight chained or branched, and each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, heteroaryl and aryl can be substituted with 1-3 substituents independently selected from halogen, -CN, -OH, -OR25, -OTs, -OMs, -O-C(O)R21, -O-C1-C6 alkyl, -COOH, -C(O)-OR22, 1,3-dioxoisoindolin-2-yl, -NH-C(O)-C1-C6 alkyl, - N(C1-C6 alkyl)-C(O)-C1-C6 alkyl, -NHR23, -N(C1-C6 alkyl)R23, -C(O)-NH-C1-C6 alkyl, - C(O)-N(C1-C6 alkyl)2, C3-C10 cycloalkyl, 4-10-membered heterocycloalkyl containing one or more groups independently selected from –NR23-, -O- or –S-, C6-C10 aryl, 5-10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S; or R1 and R2 together with the carbon atom to which they are attached may form a saturated 5-6 membered cycloalkyl or heteroaryl or aryl; which can be substituted with 1-3 substituents independently selected from halogen, -CN, -OH, -OR25, -OTs, -OMs, -O-C(O, -O-C1-C6 alkyl, -COOH, -C(O)-OR22, 1,3-dioxoisoindolin-2- yl, -NH-C(O)-C1-C6 alkyl, -N(C1-C6 alkyl)-C(O)-C1-C6 alkyl, -NHR23, -N(C1-C6 alkyl)R23, -C(O)-NH-C1- C6 alkyl, -C(O)-N(C1-C6 alkyl)2, C3-C10 cycloalkyl, 4-10-membered heterocycloalkyl containing one or more groups independently selected from –NR23-, -O- or –S-, C6-C10 aryl, 5-10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S or R1 and R4 together with the carbon atoms to which they are attached may form a partially unsaturated 5- 15-membered, preferably 5-8-membered cycloalkyl; or R1 and R4 may form a chain having 2-5 chain atoms and comprises CH2 units and / or 1-2 heteroatoms selected from N, O and S; R3 is H, C1-C4 alkyl, C6-C10 aryl, 4-methyltetrahydro-2H-pyran-2-yl; with the proviso that R1 is other than H when all R2-R4 are H R4 is H, C1-C4 alkyl, 4-methyltetrahydro-2H-pyran-2-yl; or together with R1, R4 may form cycloalkyl or chain as described above; R21 is H; C1-C4 alkyl; or C6-C10 aryl, preferably phenyl; R22 is C1-C4 alkyl, C2-C4 alkenyl or C2-C4 alkynyl; R23 is N-protecting group; R25 is O-protecting group; R5 and R6 are selected from C1-C6 alkyl, C5-C7 cycloalkyl, C6-C10 aryl, wherein each of alkyl, cycloalkyl and aryl can be substituted with one or more substituents independently selected from halogen, C1-C2 alkyl, preferably R5 and R6 are C6-C10 aryl, more preferably both aryl has at least one substituent in ortho position and said substituents of the aryls (R5 and R6) may form a direct bond between the aryls or a chain comprising CH2 units and / or a heteroatom (preferably selected from N, O and S, more preferably S), more preferably R5 and R6 are both an optionally substituted phenyl even more preferably the SR5R6 moiety is X- is a counter anion, preferably TfO-, MsO-, TsO-, TFA-, BF4-, PF6-, ClO4- , more preferably BF4- wherein the methods include the following step: (i) reacting an alkenyl sulfonium salt of Formula III-1 III-1 or a synthetic equivalent product thereof including an allyl-sulfonium of Formula III-2 III-3 III-3 or a dicationic adduct of Formula III-4 , III-4 or a mixture thereof; after reacting them first with a base to produce III-1 (procedure known to art); wherein X- and R1-R6 has the meaning as described above, both R7 is ortho-phenylene which is optionally substituted as described above at R5 and R6; with a hydride source, preferably a borane or borohydride or aluminium hydride or silane according to Formula IIIa or IIIb or IIIc or IIId or IIIe: IIIa IIIb IIIc IIId IIIe wherein, An+is a metal cation, such as Li+, Na+, Mg2+, Al3+, Ca2+, Zn2+, Ce3+, or tetrasubstituted ammonium ions, for example NH4+, NnBu4+. Y1 to Y5 are substituents that may be the same or different and selected from hydride, acetoxy-, cyano-, or a C1-C6 alkyl, or Y1 and Y2 or Y4 and Y5 together with the boron atom to which they are attached may form a saturated 5-9 membered cycloalkyl ring; (e.g., 9-borabicyclo[3.3.1]nonane) Z1 to Z5 are substituents that may be the same or different and selected from hydride, acetoxy-, cyano-, or a C1-C6 alkyl, bis(2-methoxyethoxy); Z6 to Z8 are substituents that may be the same or different and selected from hydride, C1-C6 alkyl, or phenyl; preferably, Formula IIIa is sodium borohydride, lithium borohydride, sodium cyanoborohydride, sodium acetoxyborohydride, lithium triethylborohydride, or deuterium / tritium labelled version thereof even more preferably Formula IIIa is sodium borohydride or deuterium / tritium labelled version thereof; wherein, Formula IIIb is BH3 optionally used in a form of a complex well known in the art (e.g., borane- THF complex, borane-Me2S complex) or 9-Borabicyclo[3.3.1]nonane; preferably, Formula IIIc is LiAlH4or Sodium bis(2-methoxyethoxy)aluminium hydride; preferably, Formula IIId is Diisobutylaluminium hydride; preferably, Formula IIIe is PhSiH3; preferably in the presence of an organic or inorganic proton source, more preferably in the presence of sodium bicarbonate, potassium bicarbonate, disodium phosphate, potassium bisulfate under conditions sufficient to form an alkyl sulfonium product according to Formula I. 2. Method according to point 1, further comprising the steps of (i) forming a reaction mixture comprising: - an olefin according to Formula II: wherein R1-R4 have the meaning as described in point 1, - a sulfoxide or sulfide according to Formula IIa or IIb: , IIa IIb wherein R5 and R6 have the meaning as described in point 1, more preferably the compound of formula IIa is and even more preferably an optionally substituted optionally substituted TTO), and the optional substitution is a tetrafluoro substitution (i.e., formula IIa is and the compound of formula IIb is and even more preferably an optionally substituted an optionally substituted TT), and the optional substitution is a tetrafluoro substitution (i.e., formula IIb is - an activating agent or oxidizing agent, preferably carboxylic acid anhydride in the presence of an acid or 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate), boron trifluoride, boron trifluoride etherate, trimethylsilyl trifluoromethanesulfonate, trifluoromethane sulfonic anhydride, or trifluoromethane sulfonic acid or methane sulfonic acid, optionally with trifluoroacetic anhydride or acetic anhydride, sodium tetrafluoroborate, tetra-n-butylammonium hexafluorophosphate, alkyl or aryl sulfonic acids, or combinations thereof, which might be replaced with an activating or oxidizing treatment (e.g., electrochemical oxidation), said agents and / or treatment provides X- which is preferably TfO-, MsO- , TsO-, TFA-, BF4-, PF6-, ClO4-, preferably using 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) combined with boron trifluoride or boron trifluoride diethyl etherate or lithium tetrafluoroborate or trimethylsilyl trifluoromethanesulfonate and combinations thereof, even more preferably using 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) with boron trifluoride diethyl etherate; (ii) maintaining the reaction mixture under conditions sufficient to form an alkenyl sulfonium salt of Formula III- 1, III-1 or a synthetic equivalent product including an allyl-sulfonium of Formula III-2 III-2 or a bis-adduct of Formula III-3 III-3 or a dicationic adduct of Formula III-4, if Formula IIa or IIb represent an optionally substituted TTO or TT , III-4 or a mixture thereof; wherein R7 and X- have the meaning as described above. 3. A further object of this invention is to provide methods to transform the obtained alkyl sulfonium products according to Formula I, preferably without isolation, into “anti-Markovnikov addition products” of Formula Va or Vb or Vc or Vd by reacting them with a suitable nucleophile: wherein Rm is -N3, -CN, -SCN -F, -Cl, -Br, -I, =O, -H, -D, -T; Q is N, N(CO)2, O, O(CO), O(SO), P, S, SO2; Rz, Ry, and Rx are independently moeties that do not influence the reactivity of Q, which takes part in the reaction; for example C1-C20 alkyl, preferably C1-C14 alkyl; C2-C20 alkenyl, preferably C2-C14 alkenyl; C2-C20 alkynyl, preferably C2-C14 alkynyl; C3-C10 cycloalkyl; 4-10-membered heterocycloalkyl containing one or more heteroatoms independently selected from N, O and S; C6-C14 aryl, preferably phenyl; or 5-10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S, or two Ry together with Q, when Q is N atom, to which they are attached may form a saturated, partially unsaturated or aromatic 4-7 membered heterocyclyl, and substituted versions thereof with one or more substituents defined at R1 and R2 above X- has the meaning as described above; wherein the methods include: (i) forming a reaction mixture comprising: - an alkyl sulfonium salt according to Formula I, - a nucleophile, wherein the nucleophile is selected from Formula VIa or VIb or VIc or Vid VIa VIb VIc VId or an appropriate salt thereof, and - optionally an organic or inorganic base; (ii) maintaining the reaction mixture under conditions sufficient to form the product according to Formula Va or Vb or Vc or Vd. The potential substitution of the nucleophile with an appropriate salt thereof or in situ generation thereof using a base is well known in the art. According to an alternative embodiment of the invention, R1 is H; C1-C20 alkyl, preferably C1-C14 alkyl; C2-C20 alkenyl, preferably C2-C14 alkenyl; C2-C20 alkynyl, preferably C2-C14 alkynyl; -O-C1-C20 alkyl, preferably -O-C1-C14 alkyl; -O-C2-C20 alkenyl; -O-C2-C20 alkynyl; C3-C10 cycloalkyl; 4-10-membered heterocycloalkyl containing one or more heteroatoms independently selected from N, O and S; C6-C14 aryl, preferably phenyl; or 5-10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S; and / or R2 is H, or together with R1, R2 may form cycloalkyl as described above. According to an other alternative embodiment of the invention, R1 and R2 together with the carbon atom to which they are attached may form a saturated 5-6 membered cycloalkyl. Detailed description of the invention METHODS During our research, we investigated the feasibility of a novel methodology, more specifically, the transformation of alkenyl sulfonium salts or synthetic equivalents derived from alkenes into alkyl sulfonium salts. The enabling concept behind such methodology would be interrupted Type V electrophilic reactivity of alkenyl sulfonium salts or synthetic equivalents with the nucleophilic reactivity of reductants (e.g., sodium borohydride). As no precedent was known that indicated the plausibility of this concept, we decided to study a model reaction according to the following reaction scheme: 5-(6-(1,3-dioxoisoindolin-2-yl)hex-1-en-1-yl)-5H-thianthren-5-ium tetrafluoroborate (synthesized from the corresponding alkene) was chosen as model compound and several reaction parameters were probed including the use of different reductants (1), additives (2), conditions (3), execution and workup alternatives (4) and robustness (5) to achieve the desired transformation. Then, according to the scheme above, the scope of the method was examined, including the range of suitable substrates (6) (e.g., type of alkenes, substituents, and functional groups present), acceptable sulfonium species (7), compatible activation processes (8) (e.g., activating / oxidizing agents or treatments to synthesize these species, one-pot modifications). Very importantly, a novel activation process was developed using industrially acceptable activating / oxidizing agents. Finally, further transformations of the alkyl sulfonium products prepared according to the present innovation into the overall anti-Markovnikov additions products and related compounds have been accomplished and demonstrated by non-limiting examples (9) according to the following reaction scheme:

[0002] During our studies, a significant amount of experience has been gained that underpins our discovery and several problems have been solved to achieve the expected features of this novel methodology; (1) Using sodium borohydride as a reductant is found to be a practical, industrially acceptable choice with fine- tuned reactivity. More specifically, high conversions and excellent selectivity over other reduction products is observed. The obtained yields were lower in case of boranes ((i.e., borane dimethyl sulfide complex, borane THF complex), borohydrides known for their supressed reactivity (i.e. sodium triacetoxyborohydride, sodium cyanoborohydride) or hydrides known for their increased reactivity (i.e., lithium aluminium hydride, lithium tri- sec-butylborohydride,) or other hydride sources (diisobutylaluminium hydride, LiBH4,9- borabicyclo[3.3.1]nonane). The use of hydrogen atom transfer reduction conditions (i.e., Mn(acac)3, PhSiH3) also results in product formation, however, such procedure requires work up conditions not practical on industrial scale. The equivalents of reducing reagent can vary within a wide range of values and will in general be in the range of 0.25 to 5 equiv, taking into account the number of hydride ions available from a particular reducing agent. Preferably, the reaction is conducted using equivalents of sodium borohydride reagents within the range of 0.25 to 0.50 equiv. Even more preferably, 0.35 equiv of reagent is used. Here we state that the optimal number of equivalents of reagent is dictated by the substrate in question: i.e., less reactive substrates such as internal alkenes or enol ethers generally performs better when additional equivalents of the reagent is used. In some embodiments, excess of the reagent is added in several portions at certain intervals which may result in higher yields and diminished side product formation. (2) Adding an additive acting as a proton source to protonate the evolving sulphur-ylide is appropriate to promote the desired reaction and diminish side product formation. In some embodiments, appropriate inorganic salts (i.e., sodium bicarbonate) might have the advantage of easy removal by filtration and are industrially acceptable additives. Other exemplary additives are KHCO3, Na2HPO4, and KHSO4. (3a) The methods operate well in the presence of non-nucleophilic or weakly-nucleophilic solvents or solvent mixtures. The term “non-nucleophilic solvent' is one known to those skilled in the art; in the present case, it refers to a solvent that is free from nitrogen or oxygen substituents. “Weakly nucleophilic solvents' include those which may contain nucleophilic moieties, but which moieties are less reactive or sterically hindered. Non-nucleophilic and weakly nucleophilic solvents can include water, alcohols (e.g., isopropanol), ethers (e.g., glymes, tetrahydrofuran, methyltetrahydrofuran, diethyl ether, methyl tert-buthyl ether, diisopropyl ether, dibuthyl ether or 1,4-dioxane), aliphatic hydrocarbons (e.g., hexane, heptane, petroleum ether, octane, or cyclohexane), aromatic hydrocarbons (e.g., benzene, toluene, xylene or mesitylene), halocarbons (e.g., dichloromethane, chloroform, dichloroethane), and additional polar aprotic solvents (e.g., acetonitrile, dimethylformamide, dimethyl sulfoxide), or a mixture thereof. Deuterated solvents can be also applied, like acetonitrile-d3. If only reactivity is considered, several solvents might be good alternatives, however, some might have practical advantages: e.g., acetonitrile was found to be a generally usable and industrially acceptable choice. 3b) The reaction temperature can vary within a wide range of values and will in general be in the range of -40°C to 80°C. The temperature and reaction time chosen will depend on the reactivity of the substrate and can be adjusted accordingly without difficulty. Preferably, the reaction is conducted at a temperature within the range of -20 to 50 °C. Even more preferably, the reaction is conducted at temperatures in the range of 0 to 25 °C. (3c) Empirical observations have revealed that the overreduction resulting from an excess of reducing reagent occurs gradually. Conversely, extended reaction times may lead to a gradual overreduction and decline in yields. Here we mention that reaction times required to reach full conversion may depend on the reactivity of the substrate and can be adjusted accordingly without difficulty. (3d) The pressure applied in the reactions is atmospheric in general. However, elevated pressure (e.g., 2 to 10 atm) can be useful, especially if one of the components is a gas or a highly volatile compound. (3e) The reaction concentration can vary within a wide range of values and will in general be in the range of 0.01 M to 5 M. The concentration will depend on the reactivity and solubility of the substrate and can be adjusted accordingly without difficulty. Preferably, the reaction is conducted at a concentration within the range of 0.1 to 2 M. Even more preferably, the reaction is conducted at concentrations in the range of 0.1 to 0.5 M. (4a) The order of the addition of the reactants is also interchangeable. Premixing either two of the components (sulfonium salt, reductant, and additive) and dropwise / portionwise addition of the third reactant is possible. (4b) Aqueous work-up of the reaction is not necessary; quenching of excess reagent can be practically and rapidly carried out by the addition of excess acetone. Inorganics are removed from the reaction mixture by filtration. An effective and practical way to remove different side- and by-product components of the reaction mixture is the use of crystallization or trituration. This can be explained by the large difference in polarity between the desired product in general and these different components including overreduction side products. Here we mention, that avoiding an aqueous workup and chromatography may be beneficial as the product alkyl sulfonium salts are observed to be sensitive to water. In general, the obtained residue after work-up may be partitioned between two phases (e.g., hexanes / acetonitrile), chromatographed for further purification (carried out in line with the general knowledge of a skilled person), if needed. (5) We consider the transformation of alkenyl sulfonium salts into alkyl sulfonium salts to be quite robust and not significantly sensitive to air and slightly sensitive water. As is, usage of technical grade solvents or open to air set-ups might be allowed, however, some decrease in yields might be observed. No difficulties during the scaling up of the methodology have been experienced (i.e., up to 10 mmol scale), and such operations should be achievable to those skilled in the art. (6a) As laid out above, the reaction according to the invention is applicable to alkenes which may contain various substituent patterns and different functions, like unsaturated bonds, alkyl or aryl ethers, esters, carboxylic acids, nitriles, alcohols, halogens, pseudohalogens, amides, imides and group(s), which will not be affected by the reaction. (6b) A great number of unbiased alpha-olefins (e.g., fatty olefin derivatives) can be used as starting materials in the process according to the present invention. Importantly, in these cases, anti-Markovnikov addition products (primary n-alkyl sulfonium salts) can be obtained selectively. (6c) Biased alpha-olefins (i.e., enol ethers) might also be starting materials in the process according to the present innovation. However, while there is no significant change in yields, excess reagent may be used. This is not surprising as it is known that such double bonds are more electron-rich and therefore less electrophilic. Thus, this observation is substrate-driven and characteristic of some biased olefins. (6d) 1,2-disubstituted olefins (i.e., R3 and R4 in formula II, is other than H, e.g., cyclohexene) might also be starting materials in the process according to the present innovation. (7) According to the present innovation, different sulfonium species consisting of i) alkenyl sulfonium salts; ii) allyl sulfonium salts; iii) bridged dicationic sulfonium salts; and iv) bis-adducts or a mixture thereof all might be suitable intermediates as they provide similar reaction outcomes. In other words, sulfonium salts (i-iv) can be considered synthetically equivalent. This important feature may be a cause of numerous facts including: i) bridged dicationic sulfonium salts and bis-adducts are known to be able to be transformed into the corresponding alkenyl sulfonium salts upon exposure to basic conditions; ii) the conditions of the present method are able to appropriately facilitate these transformations (i.e., the bicarbonate salt used as a proton source is also a weak base); iii) alkenyl sulfonium salts and allyl sulfonium salts may both be productive intermediates. Here we mention, that within the salt several non-nucleophilic or weakly nucleophilic counterions known in the art (e.g., triflate, tetrafluoroborate) might be acceptable. (8) Activation of an alkene, more specifically, the synthesis of alkenyl sulfonium species or synthetic equivalents may be achieved using various methods known in the art. Preferably, using an olefin according to Formula II, a sulfoxide or sulfide according to Formula IIa or IIb, and an activating agent (e.g., adding carboxylic acid anhydride in the presence of an acid) or oxidizing agent (e.g., adding 1-Chloromethyl-4-fluoro-1,4- diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) in the presence of boron trifluoride diethyl etherate), which might be replaced with an activating or oxidizing treatment (e.g., electrochemical oxidation) gives satisfactory results. In some embodiments, this activation (e.g., synthesis of an alkenyl sulfonium salt from an alkene) may be followed by additional functional group interconversions of other functional groups of the sulfonium salt obtained (while maintaining the sulfonium functionality intact) before the contact with the reducing mixture to yield alkyl sulfonium salts. According to the present innovation, using thianthrene, 1-Chloromethyl-4-fluoro-1,4- diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) in combination with boron trifluoride diethyl etherate was found to be an industrially acceptable activation mode. Importantly, we also found that the addition of boron trifluoride diethyl etherate is critical to obtain acceptable product formation in case of using 1-Chloromethyl-4- fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate). Mixing only alkene, thianthrene and 1- Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) without an additive (i.e., boron trifluoride diethyl etherate) does not result in alkenyl thianthrenium product formation or results only in traces of product formation. (9) The product alkyl sulfonium salt obtained according to the present innovation can be further transformed. A transformation of such kind could be chosen and carried out by a skilled person without difficulty. In some embodiments, this is possible without isolation and significant loss of yield. Included are transformations with commonly known nucleophiles, especially reactions including the use of primary amines, secondary amines, tertiary amines, phtalimides, azides, carboxylic acids, phenols, water, phosphines, thiols, thiocyanate, cyanide, bromide, fluoride, sulfinic acid, N-oxides, sulfoxides, hydrides (including deuterium / tritium labelled reagents) and various nucleophilic heterocycles (such scaffolds are well known in the art and could be selected by an expert; however, non-limiting examples are alkyl, alkenyl, cycloalkyl, aryl, heteroaryl and functionalized versions thereof). Examples SUMMARIZING THE SCOPE OF ALKENES (EXAMPLE 1) 1. General procedure (EXAMPLE 1) A suspension of the alkenyl thianthren-5-ium salt (0.60 mmol, 0.98 mmol, 1 equiv) and sodium bicarbonate (5.00 equiv) in anhydrous acetonitrile (0.1 M) was cooled to 0 °C under argon atmosphere. [Note 1, 2] Then sodium borohydride (0.35 equiv) was added in one portion at this temperature. After stirring the reaction mixture for 30 min – 6 h, until analysis by LC-MS indicated full conversion, [Note 3] acetone (75 equiv) was added in one portion. The resulting mixture was warmed to 25 °C and stirred at this temperature for an additional 5 min. [Note 4, 5] At this point, the reaction mixture was filtered [Note 6] and concentrated under reduced pressure. [Note 7] The residue was purified either by trituration (2 or 3 cycles) or precipitation using diethyl ether or the mixture of diethyl ether and dichloromethane (V / V = 20:1 or 10:1) [Note 8, 9] to yield the spectroscopically pure alkyl-thianthren-5-ium salt. [Note 10] [Note 1]: An ice bath was used. [Note 2]: The use of oven dried glassware is recommended as alkyl thianthren-5-ium salts may be water sensitive. [Note 3]: Using TLC analysis instead of LC-MS to indicate completion of the reaction is not reliable in most cases as Rf values of the starting materials and the products are often identical. [Note 4]: The ice bath was changed to a water bath to ensure rapid rise of temperature. [Note 5]: This step ensures quenching the excess of the reductant. [Note 6]: Water jet vacuum pumps were used. [Note 7]: The temperature of the water bath was set to 25 °C. [Note 8]: An ultrasonic bath was used in case of performing a trituration or precipitation. [Note 9]: Drying under high vacuum is often required to completely get rid of solvent residues. [Note 10]: Alkyl thianthren-5-ium salts are (moisture) sensitive alkylating agents in general that cannot be purified by column chromatography without significant losses in yields due to decomposition. For the same reason, the NMR measurements have to be carried out using oven-dried NMR tubes and anhydrous (i.e. dried by molecular sieves) non-nucleophilic deuterated solvents (i.e. DMSO-d6 is reactive). Decomposition is vividly indicated by the characteristic1H-NMR signals of thianthrene. Compound 2a (5-butyl-5H-thianthren-5-ium tetrafluoroborate) Following General procedure with the following modifications: carried out on a 0.86 mmol scale (308 mg, 1 equiv.); sodium borohydride (11.4 mg, 0.301 mmol, 0.35 equiv.), 2 h reaction time at 0 °C. Purification by trituration with diethyl ether (10 mL, 3 cycles) afforded the title compound 2a (214 mg, 0.594 mmol, 69%). Physical State: white amorphous solid1H-NMR (499.64 MHz, CDCl3): δ = 8.30 (dd, J = 7.9, 1.4 Hz, 2H), 7.83 (dd, J = 7.8, 1.3 Hz, 2H), 7.75 (td, J = 7.6, 1.3 Hz, 2H), 7.68 (td, J = 7.7, 1.4 Hz, 2H), 3.78 – 3.71 (m, 2H), 1.53 (ddd, J = 15.4, 8.9, 6.1 Hz, 2H), 1.42 (h, J = 7.4 Hz, 2H), 0.85 (t, J = 7.3 Hz, 3H).13C-NMR (125.65 MHz, CDCl3): δ = 135.6, 134.9, 134.4, 130.0, 129.9, 117.5, 40.3, 26.4, 21.2, 13.3 ppm.19F-NMR (282.21 MHz, CDCl3): δ = -151.06 (s), -151.11 ppm (s). HRMS (ESI): M+calcd. for [C16H17S2]+273.0766, found 273.0760 Compound 2b (5-(2-cyclohexylethyl)-5H-thianthren-5-ium tetrafluoroborate) Following General procedure with the following modifications: carried out on a 0.75 mmol scale (310.7 mg, 1 equiv.); sodium borohydride (10.0 mg, 0.264 mmol, 0.35 equiv.) , 1 h reaction time at 0 °C. Purification by trituration with diethyl ether (10 mL, 3 cycles) afforded the title compound 2b (236 mg, 0.57 mmol, 76%). Physical State: white amorphous solid1H-NMR (499.64 MHz, CDCl3): δ = 8.31 (dd, J = 7.9, 1.4 Hz, 2H), 7.82 (dd, J = 7.9, 1.4 Hz, 2H), 7.75 (td, J = 7.7, 1.4 Hz, 2H), 7.68 (td, J = 7.7, 1.4 Hz, 2H), 3.79 – 3.71 (m, 2H), 1.66 – 1.52 (m, 5H), 1.48 – 1.39 (m, 2H), 1.29 (ddt, J = 11.0, 7.3, 3.8 Hz, 1H), 1.18 – 0.98 (m, 3H), 0.87 – 0.74 ppm (m, 2H).13C-NMR (125.65 MHz, CDCl3): δ = 135.5, 135.0, 134.4, 130.0, 129.9, 117.7, 38.8, 36.8, 32.5, 31.3, 26.0, 25.8 ppm.19F-NMR (282.21 MHz, CDCl3): δ = -151.07 (s), -151.13 ppm (s). HRMS (ESI): M+calcd. for [C20H23S2]+327.1236, found 327.12302 Compound 2c (5-(3-phenylpropyl)-5H-thianthren-5-ium tetrafluoroborate) Following General procedure with the following modifications: carried out on a 0.76 mmol scale (318.8 mg, 1 equiv.); sodium borohydride (10.0 mg, 0.266 mmol, 0.35 equiv.), 1.5 h reaction time at 0 °C. After 1 h the reaction was not completed, therefore additional sodium borohydride (4.3 mg, 0.11 mmol, 0.15 equiv.) was added in one portion to the reaction mixture. Purification by precipitation with the mixture of diethyl ether and dichloromethane (10 mL, V / V = 10:1, 1 cycle) afforded the title compound 2c (248 mg, 0.587 mmol, 77%). Physical State: yellow amorphous solid1H-NMR (499.64 MHz, CDCl3): δ = 8.26 (dd, J = 7.9, 1.4 Hz, 2H), 7.76 (dd, J = 7.9, 1.5 Hz, 2H), 7.72 (td, J = 7.6, 1.4 Hz, 2H), 7.65 (td, J = 7.6, 1.5 Hz, 2H), 7.22 – 7.15 (m, 3H), 7.02 (dd, J = 6.9, 1.8 Hz, 2H), 3.77 – 3.70 (m, 2H), 2.72 (t, J = 7.4 Hz, 2H), 1.91 ppm (p, J = 7.6 Hz, 2H).13C-NMR (125.65 MHz, CDCl3): δ = 138.9, 135.6, 134.7, 134.4, 130.0, 129.9, 128.7, 128.4, 126.6, 117.2, 39.4, 33.5, 25.7 ppm.19F-NMR (282.21 MHz, CDCl3): δ = -150.8 (s), -150.85 ppm (s). HRMS (ESI): M+calcd. for [C21H19S2]+, 335.0923 found 335,09154 Compound 2d (5-(oct-5-en-1-yl)-5H-thianthren-5-ium tetrafluoroborate) Following General procedure with the following modifications: carried out on a 0.72 mmol scale (298.1 mg, 1 equiv.); sodium borohydride (9.6 mg, 0.25 mmol, 0.35 equiv.), 30 min reaction time at 0 °C. Purification by trituration with diethyl ether (10 mL, 3 cycles) afforded the title compound 2d (225 mg, 0.543 mmol, 75%). Physical State: white amorphous solid1H-NMR (499.64 MHz, CDCl3): δ = 8.29 (dd, J = 7.9, 1.4 Hz, 2H), 7.82 (dd, J = 7.9, 1.3 Hz, 2H), 7.75 (td, J = 7.7, 1.4 Hz, 2H), 7.67 (td, J = 7.7, 1.4 Hz, 2H), 5.71 (ddt, J = 16.9, 10.2, 6.7 Hz, 1H), 4.96 – 4.87 (m, 2H), 3.77 – 3.71 (m, 2H), 1.98 – 1.92 (m, 2H), 1.59 – 1.51 (m, 2H), 1.37 (dq, J = 9.7, 7.2 Hz, 2H), 1.31 – 1.17 ppm (m, 4H).13C-NMR (125.65 MHz, CDCl3): δ = 135.6, 134.9, 134.4, 130.0, 130.0, 117.4, 40.3, 33.6, 31.9, 27.1, 26.8, 24.3 ppm.19F-NMR (282.21 MHz, CDCl3): δ = -151.08 (s), -151.13 ppm (s). HRMS (ESI): M+calcd. for [C20H23S2]+327.1236, found 327.1241 Compound 2e (5-(5-oxo-5-(prop-2-yn-1-yloxy)undecyl)-5H-thianthren-5-ium tetrafluoroborate) Following General procedure with the following modifications: carried out on a 0.60 mmol scale (316.4 mg, 1 equiv.); sodium borohydride (8.0 mg, 0.21 mmol, 0.35 equiv.), 30 min reaction time at 0 °C. Purification by trituration with diethyl ether (10 mL, 3 cycles) afforded the title compound 2e (200 mg, 0.380 mmol, 63%). Physical State: white amorphous solid1H-NMR (499.64 MHz, CDCl3): δ = 8.30 (d, J = 7.9 Hz, 2H), 7.82 (d, J = 7.8 Hz, 2H), 7.75 (t, J = 7.6 Hz, 2H), 7.68 (t, J = 7.6 Hz, 2H), 4.66 (d, J = 2.6 Hz, 2H), 3.77 – 3.68 (m, 2H), 2.46 (t, J = 2.5 Hz, 1H), 2.32 (t, J = 7.5 Hz, 2H), 1.57 (dp, J = 26.5, 7.6 Hz, 4H), 1.42 – 1.09 ppm (m, 12H).13C-NMR (125.65 MHz, CDCl3): δ = 172.9, 135.6, 134.9, 134.4, 130.0, 129.9, 117.6, 77.8, 74.7, 51.7, 40.4, 33.9, 29.05, 28.98, 28.94, 28.88, 28.7, 27.8, 24.7, 24.5 ppm.19F-NMR (282.21 MHz, CDCl3): δ = -151.19 (s), -151.24 ppm (s). HRMS (ESI): M+calcd. for [C26H31O2S2]+439.1760, found 439.1763 Compound 2f (5-(10-methoxy-10-oxodecyl)-5H-thianthren-5-ium tetrafluoroborate) Following General procedure with the following modifications: carried out on a 9.25 mmol scale (4.50 g, 1 equiv.); sodium borohydride (122 mg, 3.24 mmol, 0.35 equiv.), 30 min reaction time at 0 °C. Purification by precipitation with the mixture of diethyl ether and dichloromethane (188 mL, V / V = 20:1, 1 cycle) afforded the title compound 2f (3.2 g, 6.6 mmol, 71%). Physical State: brown oil1H-NMR (499.64 MHz, CDCl3): δ = 8.29 (dd, J = 7.8, 1.4 Hz, 2H), 7.83 (dd, J = 7.9, 1.3 Hz, 2H), 7.75 (td, J = 7.7, 1.4 Hz, 2H), 7.67 (td, J = 7.6, 1.4 Hz, 2H), 3.76 – 3.69 (m, 2H), 3.64 (s, 3H), 2.26 (t, J = 7.5 Hz, 2H), 1.54 (h, J = 7.3 Hz, 4H), 1.35 (p, J = 7.1 Hz, 2H), 1.31 – 1.12 (m, 8H).13C-NMR (125.65 MHz, CDCl3): δ = 174.2, 135.6, 134.8, 134.4, 129.99, 129.95, 117.5, 51.4, 40.4, 34.0, 28.89, 28.88, 28.80, 28.6, 27.8, 24.8, 24.4 ppm.19F-NMR (282.21 MHz, CDCl3): δ = -151.0 (s), -151.0 ppm (s). M+calcd. for [C23H29O2S2]+401.1603, found 401.1602 Compound 2g (5-(6-(benzoyloxy)hexyl)-5H-thianthren-5-ium tetrafluoroborate) Following General procedure with the following modifications: carried out on a 0.75 mmol scale (377.0 mg, 1 equiv.); sodium borohydride (9.9 mg, 0.26 mmol, 0.35 equiv.) 1 h reaction time at 0 °C. Purification by precipitation with the mixture of diethyl ether and dichloromethane (10 mL, V / V = 10:1, 1 cycle) afforded the title compound 2g (196 mg, 0.386 mmol, 52%). Physical State: white amorphous solid1H-NMR (499.64 MHz, CDCl3): δ = 8.27 (dd, J = 7.8, 1.4 Hz, 2H), 7.98 (d, J = 7.2 Hz, 2H), 7.81 (dd, J = 7.9, 1.5 Hz, 2H), 7.74 (td, J = 7.7, 1.4 Hz, 2H), 7.66 (td, J = 7.6, 1.4 Hz, 2H), 7.56 – 7.51 (m, 1H), 7.42 (t, J = 7.7 Hz, 2H), 4.22 (t, J = 6.5 Hz, 2H), 3.78 – 3.71 (m, 2H), 1.67 (p, J = 6.8 Hz, 2H), 1.59 (p, J = 7.6 Hz, 2H), 1.51 – 1.42 (m, 2H), 1.37 ppm (q, J = 7.3 Hz, 2H).13C-NMR (125.65 MHz, CDCl3): δ = 166.5, 135.6, 134.7, 134.5, 132.9, 130.3, 130.0, 129.5, 128.3, 117.3, 64.5, 40.3, 28.2, 27.4, 25.3, 24.3 ppm.19F-NMR (282.21 MHz, CDCl3): δ = -150.91 (s), -150.97 ppm (s). HRMS (ESI): M+calcd. for [C25H25O2S2]+421.1290, found 421.1304 Compound 2h (5-(4-cyanopentyl)-5H-thianthren-5-ium tetrafluoroborate) Following General procedure with the following modifications: carried out on a 0.77 mmol scale (304.7 mg, 1 equiv.); sodium borohydride (10.2 mg, 0.269 mmol, 0.35 equiv.), 1.5 h reaction time at 0 °C. After 1 h the reaction was not completed, therefore additional sodium borohydride (4.4 mg, 0.12 mmol, 0.15 equiv) was added in one portion to the reaction mixture. Purification by trituration with diethyl ether (10 mL, 3 cycles) afforded the title compound 2h (222 mg, 0.556 mmol, 73%). Physical State: yellow amorphous solid1H-NMR (499.64 MHz, CDCl3): δ = 8.29 (dd, J = 7.9, 1.3 Hz, 2H), 7.84 (dd, J = 7.9, 1.3 Hz, 2H), 7.77 (td, J = 7.7, 1.4 Hz, 2H), 7.70 (td, J = 7.6, 1.4 Hz, 2H), 3.78 (dd, J = 8.8, 6.3 Hz, 2H), 2.35 (t, J = 6.7 Hz, 2H), 1.65 (m, 4H), 1.61 – 1.55 ppm (m, 2H).13C-NMR (125.65 MHz, CDCl3): δ = 135.6, 134.8, 134.6, 130.1, 130.1, 119.5, 117.2, 40.1, 26.5, 24.4, 23.6, 16.6 ppm.19F-NMR (282.21 MHz, CDCl3): δ = -150.77 (s), -150.82 ppm (s). HRMS (ESI): M+calcd. for [C18H18NS2]+, 312.0875 found 312.0876 Compound 2i (5-(6-(1,3-dioxoisoindolin-2-yl)hexyl)-5H-thianthren-5-ium tetrafluoroborate) Following General procedure with the following modifications: carried out on a 0.60 mmol scale (318.5 mg, 1 equiv.); sodium borohydride (7.9 mg, 0.21 mmol, 0.35 equiv.), 30 min reaction time at 0 °C. Purification by precipitation with the mixture of diethyl ether and dichloromethane (10 mL, V / V = 20:1, 1 cycle) afforded the title compound 2i (265 mg, 0.497 mmol, 83%). Physical State: white amorphous solid1H-NMR (499.64 MHz, CDCl3): δ = 8.32 (dd, J = 7.9, 1.4 Hz, 2H), 7.83 – 7.79 (m, 4H), 7.76 – 7.65 (m, 6H), 3.77 – 3.71 (m, 2H), 3.60 (t, J = 7.0 Hz, 2H), 1.58 – 1.52 (m, 3H), 1.43 (p, J = 7.5 Hz, 2H), 1.29 – 1.23 ppm (m, 3H).13C-NMR (125.65 MHz, CDCl3): δ = 168.3, 135.6, 134.9, 134.4, 133.9, 132.1, 130.01, 129.97, 123.2, 117.4, 40.2, 37.5, 28.0, 27.2, 25.9, 24.3 ppm.19F-NMR (282.21 MHz, CDCl3): δ = -151.13 (s), -151.18 ppm (s). HRMS (ESI): M+calcd. for +446.1243, found 446.1244 Compound 2k (5-(3-(3-phenylpropoxy)propyl)-5H-thianthren-5-ium tetrafluoroborate) Following General procedure with the following modifications: carried out on a 0.72 mmol scale (342.7 mg, 1 equiv.); sodium borohydride (9.5 mg, 0.25 mmol, 0.35 equiv.), 30 min reaction time at 0 °C. Purification by trituration with diethyl ether (10 mL, 3 cycles) afforded the title compound 2k (227 mg, 0.473 mmol, 66%). Physical State: white amorphous solid1H-NMR (499.64 MHz, CDCl3): δ = 8.29 (d, J = 8.2 Hz, 2H), 7.80 (d, J = 7.9 Hz, 2H), 7.72 (t, J = 7.7 Hz, 2H), 7.65 (t, J = 7.8 Hz, 2H), 7.29 – 7.24 (m, 2H), 7.19 – 7.14 (m, 3H), 3.88 (t, J = 7.0 Hz, 2H), 3.54 (t, J = 5.4 Hz, 2H), 3.45 (t, J = 6.6 Hz, 2H), 2.64 (t, J = 7.8 Hz, 2H), 1.93 – 1.85 (m, 2H), 1.82 ppm (p, J = 6.4 Hz, 2H). (see Spectrum)13C-NMR (125.65 MHz, CDCl3): δ = 141.8, 135.6, 135.1, 134.3, 129.9, 129.8, 128.4 (2C), 125.8, 117.7, 70.6, 68.1, 38.9, 32.3, 31.2, 24.9 ppm.19F-NMR (282.21 MHz, CDCl3): δ = -151.19 (s), -151.24 ppm (s). HRMS (ESI): M+calcd. for [C24H25OS2]+393,1341, found 393.1330 Compound 2l (5-(6-chlorohexyl)-5H-thianthren-5-ium tetrafluoroborate) Following General procedure with the following modifications: carried out on a 0.87 mmol scale (364.2 mg, 1 equiv.); sodium borohydride (11.5 mg, 0.303 mmol, 0.35 equiv.), 30 min reaction time at 0 °C. Purification by trituration with diethyl-ether (10 mL, 3 cycles) afforded the title compound 2l (224 mg, 0.577 mmol, 67%). Physical State: white solid1H-NMR (499.64 MHz, CDCl3): δ = 8.30 (dd, J = 7.8, 1.4 Hz, 2H), 7.83 (dd, J = 7.9, 1.3 Hz, 2H), 7.76 (td, J = 7.7, 1.4 Hz, 2H), 7.69 (td, J = 7.7, 1.4 Hz, 2H), 3.80 – 3.72 (m, 2H), 3.48 (t, J = 6.4 Hz, 2H), 1.68 (p, J = 6.7 Hz, 2H), 1.58 (p, J = 7.4 Hz, 2H), 1.48 – 1.32 ppm (m, 4H).13C-NMR (125.65 MHz, CDCl3): δ = 135.6, 134.9, 134.4, 130.0, 130.0, 117.5, 44.8, 40.3, 31.8, 26.9, 25.9, 24.3 ppm.19F-NMR (282.21 MHz, CDCl3): δ = -151.01 (s), -151.06 ppm (s). HRMS (ESI): M+calcd. for [C18H20ClS2]+335.0689, found 335.0687 Compound 2m (5-(6-bromohexyl)-5H-thianthren-5-ium tetrafluoroborate) Following General procedure with the following modifications: carried out on a 0.77 mmol scale (360.0 mg, 1 equiv.); sodium borohydride (10.3 mg, 0.271 mmol, 0.35 equiv.), 1 h reaction time at 0 °C. Purification by trituration with diethyl ether (10 mL, 3 cycles) afforded the title compound 2m (175 mg, 0.375 mmol, 48%). Physical State: white solid1H-NMR (499.64 MHz, CDCl3): δ = 8.31 (dd, J = 7.9, 1.4 Hz, 2H), 7.83 (dd, J = 7.9, 1.3 Hz, 2H), 7.76 (td, J = 7.7, 1.4 Hz, 2H), 7.69 (td, J = 7.6, 1.3 Hz, 2H), 3.81 – 3.72 (m, 2H), 3.35 (t, J = 6.6 Hz, 2H), 1.77 (p, J = 6.8 Hz, 2H), 1.58 (p, J = 7.1 Hz, 2H), 1.50 – 1.32 ppm (m, 4H).13C-NMR (125.65 MHz, CDCl3): δ = 138.5, 135.6, 134.9, 134.4, 130.0, 129.9, 117.5, 114.5, 40.4, 33.4, 28.3, 28.2, 27.7, 24.4 ppm.19F-NMR (282.21 MHz, CDCl3): δ = -150.97 (s), -151.03 ppm (s). HRMS (ESI): M+calcd. for [C18H20BrS2]+379.0184, found 379.0174 Compound 2n (5-(6-(1,3-dioxoisoindolin-2-yl)hexyl)-5H-thianthren-5-ium tetrafluoroborate) Following General procedure with the following modifications: carried out on a 0.71 mmol scale (432.3 mg, 1 equiv.); sodium borohydride (9.3 mg, 0.25 mmol, 0.35 equiv.), 1.5 h reaction time at 0 °C. After 1 h the reaction was not completed, therefore additional sodium borohydride (4.0 mg, 0.11 mmol, 0.15 equiv.) was added in one portion to the reaction mixture. Purification by trituration with diethyl ether (10 mL, 3 cycles) afforded the title compound 2n (230 mg, 0.375 mmol, 53%) Physical State: white amorphous solid1H-NMR (499.64 MHz, CDCl3): δ = 8.31 (dd, J = 7.8, 1.4 Hz, 2H), 7.82 (dd, J = 7.9, 1.4 Hz, 2H), 7.80 – 7.72 (m, 4H), 7.68 (td, J = 7.7, 1.4 Hz, 2H), 7.35 (d, J = 8.2 Hz, 2H), 4.00 (t, J = 6.4 Hz, 2H), 3.78 – 3.69 (m, 2H), 2.45 (s, 3H), 1.66 – 1.49 (m, 4H), 1.41 – 1.11 (m, 12H).13C-NMR (125.65 MHz, CDCl3): δ = 144.7, 135.6, 134.7, 134.5, 130.0, 129.8, 128.7, 127.8, 127.6, 117.4, 70.7, 40.4, 28.9, 28.8, 28.7, 28.6, 28.5, 27.7, 25.2, 24.4, 21.6 ppm.19F-NMR (282.21 MHz, CDCl3): δ = -151.0 (s), -151.1 ppm (s). HRMS (ESI): M+calcd. for [C29H35O3S3]+527.1743, found 527.1746 Compound 2o (5-cyclopentyl-5H-thianthren-5-ium tetrafluoroborate) Following General procedure with the following modifications: carried out on a 0.88 mmol scale (326.3 mg, 1 equiv.); sodium borohydride (11.7 mg, 0.309 mmol, 0.35 equiv.), 1.5 h reaction time at 0 °C. After 1 h the reaction was not completed, therefore additional sodium borohydride (5.0 mg, 0.13 mmol, 0.15 equiv.) was added in one portion to the reaction mixture. Purification by trituration with diethyl ether (10 mL, 3 cycles) afforded the title compound 2o (189 mg, 0.508 mmol, 58%). Physical State: white solid1H-NMR (499.64 MHz, CDCl3): δ = 8.28 (dd, J = 7.9, 1.3 Hz, 2H), 7.82 (d, J = 7.9 Hz, 2H), 7.79 – 7.73 (m, 2H), 7.66 (t, J = 7.6 Hz, 2H), 4.64 (p, J = 6.4 Hz, 1H), 2.09 – 1.98 (m, 2H), 1.97 – 1.86 (m, 2H), 1.71 ppm (m, 5H).13C-NMR (125.65 MHz, CDCl3): δ = 135.6, 134.8, 134.5, 129.9, 129.9, 118.0, 52.9, 29.5, 24.8 ppm.19F-NMR (282.21 MHz, CDCl3): δ = -150.93 (s), -150.98 ppm (s). HRMS (ESI): M+calcd. for [C17H17S2]+285.0766, found 285.0757 Compound 2p (5-cyclohexyl-5H-thianthren-5-ium tetrafluoroborate) Following General procedure with the following modifications: carried out on a 0.82 mmol scale (314.6 mg, 1 equiv.); sodium borohydride (10.8 mg, 0.287 mmol, 0.35 equiv.), 1.5 h reaction time at 0 °C. After 1 h the reaction was not completed, therefore additional sodium borohydride (4.7 mg, 0.13 mmol, 0.15 equiv.) was added in one portion to the reaction mixture. Purification by trituration with diethyl ether (10 mL, 3 cycles) afforded the title compound 2p (210 mg, 0.544 mmol, 66%). Physical State: white solid1H-NMR (499.64 MHz, CDCl3): δ = 8.29 (dd, J = 7.9, 1.3 Hz, 2H), 7.82 (dd, J = 7.9, 1.4 Hz, 2H), 7.76 (td, J = 7.7, 1.4 Hz, 2H), 7.67 (td, J = 7.7, 1.4 Hz, 2H), 4.22 (tt, J = 11.3, 3.9 Hz, 1H), 1.94 – 1.78 (m, 4H), 1.61 (m, 1H), 1.56 – 1.48 (m, 2H), 1.43 – 1.32 (m, 1H), 1.26 – 1.15 ppm (m, 2H).13C-NMR (125.65 MHz, CDCl3): δ = 135.6, 135.5, 134.4, 129.9, 129.8, 116.7, 54.3, 27.7, 25.1, 24.2 ppm.19F-NMR (282.21 MHz, CDCl3): δ = -150.75 (s), -150.80 ppm (s). HRMS (ESI): M+calcd. for [C18H19S2]+299,0923, found 299,0913 Compound 2q (5-(tetrahydro-2H-pyran-3-yl)-5H-thianthren-5-ium tetrafluoroborate) Following General procedure with the following modifications: carried out on a 0.83 mmol scale (320.1 mg, 1 equiv.); sodium borohydride (11.0 mg, 0.290 mmol, 0.35 equiv.), 5.5 h reaction time at 0 °C. After 1 h the reaction was not completed, therefore additional sodium borohydride (4.7 mg, 0.12 mmol, 0.15 equiv.) was added in one portion to the reaction mixture. This cycle was repeated 4 times until full conversion was observed. Purification by trituration with diethyl ether (10 mL, 3 cycles) afforded the title compound 2q (165 mg, 0.425 mmol, 51%). Physical State: white solid1H-NMR (499.64 MHz, CDCl3): δ = 8.34 (dd, J = 8.0, 1.4 Hz, 1H), 8.21 (dd, J = 8.0, 1.4 Hz, 1H), 7.85 (dt, J = 8.0, 1.3 Hz, 2H), 7.78 (tt, J = 7.7, 1.7 Hz, 2H), 7.71 (td, J = 7.6, 1.4 Hz, 1H), 7.67 (td, J = 7.7, 1.4 Hz, 1H), 4.51 (ddd, J = 10.9, 6.4, 3.1 Hz, 1H), 3.86 (ddd, J = 10.9, 6.7, 3.8 Hz, 1H), 3.77 – 3.63 (m, 3H), 2.18 – 2.08 (m, 1H), 2.04 (dt, J = 12.4, 6.1 Hz, 1H), 1.89 (td, J = 8.8, 4.0 Hz, 1H), 1.72 – 1.60 ppm (m, 1H).13C-NMR (125.65 MHz, CDCl3): δ = 136.2, 136.0, 135.4, 135.0, 134.73, 134.68, 130.3, 130.2, 130.1, 129.9, 116.0, 115.9, 68.2, 66.1, 51.7, 24.3, 23.2 ppm.19F-NMR (282.21 MHz, CDCl3): δ = -151.19 (s), -151.24 ppm (s). HRMS (ESI): M+calcd. for [C17H17OS2]+301.0715, found 301.0711 Compound 2r (5-(sec-butyl)-5H-thianthren-5-ium tetrafluoroborate) from the (Z)-alkene: Following General procedure with the following modifications: carried out on a 0.98 mmol scale (350.6 mg, 1 equiv.); sodium borohydride (13.0 mg, 0.343 mmol, 0.35 equiv.), 1.5 h reaction time at 0 °C. After 1 h the reaction was not completed, therefore additional sodium borohydride (5.6 mg, 0.15 mmol, 0.15 equiv.) was added in one portion to the reaction mixture. Purification by precipitation with the mixture of diethyl ether and dichloromethane (10 mL, V / V = 10:1, 1 cycle) afforded the title compound 2r (167 mg, 0.464 mmol, 47%). from the (E)-alkene: Following General procedure with the following modifications: carried out on a 0.98 mmol scale (350.5 mg, 1 equiv.); sodium borohydride (13.0 mg, 0.343 mmol, 0.35 equiv.), 1.5 h reaction time at 0 °C. After 1 h the reaction was not completed, therefore additional sodium borohydride (5.6 mg, 0.15 mmol, 0.15 equiv.) was added in one portion to the reaction mixture. Purification by precipitation with the mixture of diethyl ether and dichloromethane (10 mL, V / V = 10:1, 1 cycle) afforded the title compound 2r (173 mg, 0.481 mmol, 49%). Physical State: white solid1H-NMR (499.64 MHz, CDCl3): δ = 8.36 (dd, J = 7.8, 1.4 Hz, 1H), 8.32 (dd, J = 7.9, 1.4 Hz, 1H), 7.82 (ddd, J = 7.8, 4.2, 1.4 Hz, 2H), 7.76 (tdd, J = 7.8, 2.9, 1.4 Hz, 2H), 7.69 (tt, J = 7.6, 1.7 Hz, 2H), 4.36 – 4.26 (m, 1H), 1.85 – 1.77 (m, 1H), 1.59 (ttt, J = 14.8, 7.5, 3.3 Hz, 1H), 1.33 (d, J = 6.8 Hz, 3H), 0.98 ppm (t, J = 7.4 Hz, 3H).13C-NMR (125.65 MHz, CDCl3): δ = 135.8, 135.7, 134.5, 134.4, 130.0, 130.0, 129.9, 129.8, 128.7, 127.7, 117.4, 52.9, 24.5, 14.6, 10.3 ppm.19F-NMR (282.21 MHz, CDCl3): δ = -150.6 (s), -150.7 (s) ppm. HRMS (ESI): M+calcd. for [C16H17S2]+273.0766, found 273.0762 Compound 2s (5-(hexan-3-yl)-5H-thianthren-5-ium tetrafluoroborate) from (Z)-alkene: Following General procedure with the following modifications: carried out on a 0.90 mmol scale (350.5 mg, 1 equiv.); sodium borohydride (12.0 mg, 0.318 mmol, 0.35 equiv.), 3.5 h reaction time at 0 °C. After 1 h the reaction was not completed, therefore additional sodium borohydride (5.2 mg, 0.14 mmol, 0.15 equiv.) was added in one portion to the reaction mixture. This cycle was repeated 3 times until full conversion was observed. Purification by precipitation with the mixture of diethyl ether and dichloromethane (10 mL, V / V = 10:1, 1 cycle) afforded the title compound 2s (63 mg, 0.162 mmol, 18 %). from (E)-alkene: Following General procedure with the following modifications: carried out on a 0.78 mmol scale (300.5 mg 1 equiv.); sodium borohydride (10.3 mg, 0.272 mmol, 0.35 equiv.), 1.5 h reaction time at 0 °C. After 1 h the reaction was not completed, therefore additional sodium borohydride (4.4 mg, 0.12 mmol, 0.15 equiv.) was added in one portion to the reaction mixture. Purification by precipitation with the mixture of diethyl ether and dichloromethane (10 ml, V / V = 10:1, 1 cycle) afforded the title compound 2s (31 mg, 0.080 mmol, 10%). Physical State: white solid1H NMR (499.64 MHz, Acetonitrile-d3): δ = 8.12 (d, J = 7.9 Hz, 2H), 7.99 (d, J = 7.8 Hz, 2H), 7.91 – 7.85 (m, 2H), 7.78 – 7.72 (m, 2H), 4.46 (tt, J = 7.9, 4.1 Hz, 1H), 2.02 – 1.96 (m, 2H), 1.70 – 1.58 (m, 2H), 0.98 (t, J = 7.4 Hz, 3H), 0.81 (t, J = 7.2 Hz, 3H). Compound 2t (5-phenethyl-5H-thianthren-5-ium tetrafluoroborate) Following General procedure with the following modifications: carried out on a 0.74 mmol scale (300 mg, 1 equiv.); sodium borohydride (9.8 mg, 0.258 mmol, 0.35 equiv.), 5.5 h reaction time at 0 °C. After 1 h the reaction was not completed, therefore additional sodium borohydride (5.6 mg, 0.148 mmol, 0.20 equiv.) was added in one portion to the reaction mixture. Purification by precipitation with the mixture of diethyl ether and dichloromethane (10 mL, V / V = 10:1, 2 cycle) afforded the title compound 2t (150 mg, 0.738 mmol, 50%). Physical State: brown solid Spectral and physical properties were in accordance with those reported in the literature. (Ref 2) SUMMARIZING THE REACTIONS OF ALKYL THIANTHRENIUM SALTS (EXAMPLES 2-4) Fig.3. Scope of the anti-Markovnikov hydrofunctionalization. Alkyl thianthren-5-ium salt (0.41-0.70 mmol, 1 equiv.) in anhydrous acetonitrile (0.1 M) , nucleophile (5 equiv.), base (if indicated, 5.00 equiv.), tetrabutylammonium tetrafluoroborate (if indicated, 0.10 equiv) at 25-70 °C for 2.5-18h a) Yield determined by 1H nuclear magnetic resonance analysis of the crude reaction mixture; b) base was used; c) Higher temperature was used; d) tetrabutylammonium tetrafluoroborate (10 mol%) was used General procedure (EXAMPLE 2) To the solution of the alkyl thianthren-5-ium salt [Note 1] (0.41-0.70 mmol, 1 equiv.) in anhydrous acetonitrile (0.1 M) were added the indicated nucleophile (5 equiv.), base (if indicated, 5.00 equiv.) and tetrabutylammonium tetrafluoroborate (if indicated, 0.10 equiv.) and the reaction mixture was stirred at 25-70 °C for 2.5-18 h. [Note 3] After analysis by TLC or LC-MS indicated the completion of the reaction [Note 4]. Dichloromethane (50 ml) and saturated brine (50 ml) were added to the reaction mixture. The phases were separated, and the aqueous layer was extracted with dichloromethane (3x 50 mL). The combined organic layers were dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure [Note 5, 6, 7]. The residue was purified by flash column chromatography to afford the pure products. [Note 1]: The use of oven dried glassware is recommended as alkyl thianthren-5-ium salts may be water sensitive. [Note 2]: A heating block was used. [Note 3]: The exact external temperature is noted in every case. [Note 4]: The reaction can usually be monitored by TLC, however in some cases the products are not UV active and a stain should be used. The reaction can also be followed by LC-MS. [Note 5]: The temperature of the water bath was set to 25 °C [Note 6]: In the cases, where an external base was not used (e.g. amine nucleophiles, phosphines), no aqueous work up was carried out and the crude reaction mixture was directly concentrated under reduced pressure. [Note 7]: At this point, NMR yield was measured as follows: 1,3,5-trimethylbenzene was added as an internal standard to the residue and the mixture formed was fully dissolved in deuterated chloroform.1H NMR yield was then measured using samples from this solution.

[0003] Compound 3 (methyl 10-(phenylamino)decanoate) Following General Procedure with the following modifications: carried out on a 0.41 mmol scale using aniline (189 µl, 2.07 mmol, 5.00 equiv.) as the nucleophile in acetonitrile (4.1 mL, 0.1 M) for 18 h at 25 °C. The reaction mixture was directly concentrated under reduced pressure and no aqueous workup was carried out. Purification by flash column chromatography on flash silica gel (0% ethyl-acetate in hexanes grading to 25% ethyl-acetate in n-hexanes) afforded the title compound 3 (62 mg, 0.22 mmol, 54%, 61% NMR yield). Physical State: pale yellow solid1H-NMR (499.64 MHz, CDCl3): δ =1H NMR (500 MHz, cdcl3) δ 7.19 – 7.14 (m, 2H), 6.68 (tt, J = 7.3, 1.1 Hz, 1H), 6.62 – 6.58 (m, 2H), 3.67 (s, 3H), 3.58 (s, 1H), 3.10 (t, J = 7.1 Hz, 2H), 2.30 (t, J = 7.5 Hz, 2H), 1.61 (p, J = 7.1 Hz, 4H), 1.39 ppm (t, J = 7.5 Hz, 2H), 1.32 (d, J = 6.3 Hz, 8H).13C-NMR (125.65 MHz, CDCl3): δ = 174.3, 148.5, 129.2, 117.1, 112.7, 51.4, 44.0, 34.1, 29.6, 29.3 (2C), 29.2, 29.1, 27.1, 24.9 ppm. HRMS (ESI): [M+H]+calcd. for [C17H28NO2]+278.2115, found 278.2111 TLC: Rf = 0.43 (13 % ethyl-acetate in hexanes, CAM) Compound 4 (methyl 10-(benzylamino)decanoate) Following General Procedure with the following modifications: carried out on a 0.49 mmol scale using benzylamine (267 µl, 2.45 mmol, 5.00 equiv.) as the nucleophile in acetonitrile (4.9 mL, 0.1 M) for 18 h at 25 °C. The reaction mixture was directly concentrated under reduced pressure and no aqueous workup was carried out. Purification by flash column chromatography on flash alumina gel (0% methanol in dichloromethane grading to 10% methanol in dichloromethane) afforded the title compound 4 (80 mg, 0.27 mmol, 56%, 58% NMR yield.) Physical State: yellow oil1H-NMR (499.64 MHz, CDCl3): δ = 7.35 – 7.30 (m, 4H), 7.28 – 7.23 (m, 1H), 3.94 (s, 1H), 3.81 (s, 2H), 3.66 (s, 3H), 2.67 – 2.60 (m, 2H), 2.29 (t, J = 7.5 Hz, 2H), 1.61 (p, J = 7.1 Hz, 2H), 1.53 (p, J = 7.2 Hz, 2H), 1.28 ppm (d, J = 7.1 Hz, 10H).13C-NMR (125.65 MHz, CDCl3): δ = 174.2, 138.8, 128.5 (4C), 127.2, 53.3, 51.4, 48.7, 34.1, 29.34, 29.29, 29.2, 29.12, 29.07, 27.2, 24.9 ppm. HRMS (ESI): [M+H]+calcd. for [C18H30NO2]+292.2271 , found 292.2270 TLC: Rf = 0.75 (3% methanol in dichloromethane, iodine chamber, then o-toluidine) Compound 5 (methyl 10-(benzyl(methyl)amino)decanoate) Following General Procedure with the following modifications: carried out on a 0.41 mmol scale using N- benzylmethylamine (330 µl, 2.54 mmol, 5.00 equiv.) as the nucleophile in acetonitrile (5.1 mL, 0.1 M) for 18 h at 25 °C. The reaction mixture was directly concentrated under reduced pressure and no aqueous workup was carried out. Purification by flash column chromatography on flash silica gel (0% acetone in hexanes grading to 25% acetone in hexanes) afforded the title compound 5 (126 mg, 0.412 mmol, 81%, 83% NMR yield). Physical State: yellow oil1H-NMR (499.64 MHz, CDCl3): δ = 7.31 (d, J = 4.3 Hz, 4H), 7.23 (dt, J = 8.8, 4.3 Hz, 1H), 3.67 (s, 3H), 3.48 (s, 2H), 2.39 – 2.33 (m, 2H), 2.30 (t, J = 7.5 Hz, 2H), 2.18 (s, 3H), 1.66 – 1.56 (m, 2H), 1.50 (p, J = 7.1 Hz, 2H), 1.35 – 1.23 ppm (m, 10H).13C-NMR (125.65 MHz, CDCl3): δ = 174.3, 138.8 (br s), 129.1, 128.2, 127.0, 62.2, 57.4, 51.4, 42.1, 34.1, 29.44, 29.36, 29.2, 29.1, 27.4, 27.2, 24.9 ppm. HRMS (ESI): [M+H]+calcd. for [C19H32NO2]+306.2428, found 306.2425 TLC: Rf = 0.38 (16% acetone in hexanes, iodine chamber, then o-toluidine) Compound 6 (N,N,N-triethyl-10-methoxy-10-oxodecan-1-aminium tetrafluoroborate) Following General Procedure with the following modifications: carried out on a 0.46 mmol scale using triethylamine (324 µl, 2.32 mmol, 5.00 equiv.) as the nucleophile in acetonitrile (4.6 mL, 0.1 M) for 2.5 h at 25 °C. The reaction mixture was directly concentrated under reduced pressure and no aqueous workup was carried out. Purification by precipitation with the mixture of diethyl ether and dichloromethane (V / V = 5:1), and the residue was washed with diethyl ether (3 × 10 mL) afforded the title compound 6 (140 mg, 0.375 mmol, 81%). Physical State: pale brown solid1H-NMR (499.64 MHz, CDCl3): δ = 3.66 (s, 3H), 3.32 (q, J = 7.3 Hz, 6H), 3.16 – 3.10 (m, 2H), 2.30 (t, J = 7.5 Hz, 2H), 1.71 – 1.58 (m, 4H), 1.44 – 1.22 ppm (m, 19H).13C-NMR (125.65 MHz, CDCl3): δ = 174.2, 57.0, 52.9, 51.3, 33.9, 29.0, 28.90, 28.88, 28.85, 26.2, 24.8, 21.6, 7.3 ppm19F-NMR (282.21 MHz, CDCl3): δ = -152.19 (s), -152.24 ppm (s). HRMS (ESI): M+calcd. for [C17H36NO2]+286.2741, found 286.2741 TLC: Rf = 0.60 (10% methanol in dichloromethane, CAM) Compound 7 (methyl 10-(1,3-dioxoisoindolin-2-yl)decanoate) Following General Procedure with the following modifications: carried out on a 0.49 mmol scale using potassium phthalimide (465 mg, 2.46 mmol, 5.00 equiv.) as the nucleophile and tetrabutylammonium tetrafluoroborate (16 mg, 0.049 mmol, 0.10 equiv.) as additive in acetonitrile (4.9 mL, 0.1 M) for 18 h at 25 °C. Purification by flash column chromatography on flash silica gel (0% ethyl-acetate in hexanes grading to 20 % ethyl-acetate in hexanes) afforded the title compound 7 (114 mg, 0.344 mmol, 70%, 79 % NMR yield) Physical State: pale yellow solid1H-NMR (499.64 MHz, CDCl3): δ = 7.81 (dd, J = 5.4, 3.0 Hz, 2H), 7.68 (dd, J = 5.5, 3.0 Hz, 2H), 3.68 – 3.62 (m, 5H), 2.27 (t, J = 7.5 Hz, 2H), 1.65 (q, J = 7.4 Hz, 2H), 1.57 (p, J = 7.3 Hz, 2H), 1.34 – 1.22 ppm (m, 10H).13C-NMR (125.65 MHz, CDCl3): δ = 174.2, 168.4, 133.7, 132.2, 123.1, 51.3, 38.0, 34.0, 29.2, 29.1, 29.0 (2C), 28.5, 26.7, 24.9 ppm. HRMS (ESI): [M+H]+calcd. for [C19H26NO4]+332.1856, found 332.1858 TLC: Rf = 0.69 (25% ethyl-acetate in hexanes, KMnO4) Compound 8 (methyl 10-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)decanoate) Following General Procedure with the following modifications: carried out on a 0.61 mmol scale using theophylline (110 mg, 0.609 mmol, 1.00 equiv.) as the nucleophile and potassium carbonate (421 mg, 3.05 mmol, 5.00 equiv.) as the base in acetonitrile (6.1 mL, 0.1 M) for 18 h at 50 °C. Purification by flash column chromatography on flash silica gel (0% methanol in dichloromethane grading to 10% methanol in dichloromethane) afforded the title compound 8 (184 mg, 0.505 mmol, 83%). Physical State: brown solid1H-NMR (599.63 MHz, CDCl3): δ = 7.52 (s, 1H), 4.26 (t, J = 7.2 Hz, 2H), 3.65 (s, 3H), 3.58 (s, 3H), 3.40 (s, 3H), 2.28 (t, J = 7.5 Hz, 2H), 1.85 (p, J = 7.2 Hz, 2H), 1.60 (q, J = 7.1 Hz, 2H), 1.35 – 1.21 ppm (m, 10H).13C-NMR (150.79 MHz, CDCl3): δ = 174.2, 155.1, 151.7, 148.9, 140.7, 107.0, 51.4, 47.3, 34.0, 30.8, 29.7, 29.2, 29.1, 29.0, 28.9, 28.0, 26.3, 24.8 ppm.15N-NMR (40.52 MHz, CDCl3): δ = -151.1, -211.9, -229.8, -266.8 ppm. HRMS (ESI): [M+Na]+calcd. for [C18H28N4O4Na]+387.2003, found 387.1994 TLC: Rf = 0.82 (5% methanol in dichloromethane, KMnO4) Compound 9 (methyl 10-azidodecanoate) Following General Procedure with the following modifications: carried out on a 0.42 mmol scale using sodium azide (135 mg, 2.08 mmol, 5.00 equiv.) as the nucleophile and tetrabutylammonium tetrafluoroborate (20.6 mg, 62.5 µmol, 0.15 equiv.) as additive in acetonitrile (4.2 mL, 0.1 M) for 18 h at 25 °C. Purification by flash column chromatography on flash silica gel (0% ethyl-acetate in n-hexanes grading to 20 % ethyl-acetate in hexanes) afforded the title compound 9 (62.0 mg, 273 µmol, 65%, 71% NMR yield). Physical State: colorless oil1H-NMR (499.64 MHz, CDCl3): δ = 3.66 (s, 3H), 3.25 (t, J = 7.0 Hz, 2H), 2.30 (t, J = 7.5 Hz, 2H), 1.66 – 1.55 (m, 4H), 1.40 – 1.27 ppm (m, 10H).13C-NMR (125.65 MHz, CDCl3): δ = 174.2, 51.5, 34.1, 29.2, 29.10, 29.06, 29.04, 28.8, 26.7, 24.9 ppm. HRMS (ESI): [M-N2+H]+calcd. for [C11H21NO2]+199.2940, found 200.1640 [M+H –N2]+TLC: Rf = 0.54 (13% ethyl-acetate in hexanes, KMnO4) Compound 10 (methyl 10-acetoxydecanoate) Following General Procedure with the following modifications: carried out on a 0.57 mmol scale using potassium acetate (282 mg, 2.87 mmol, 5.00 equiv.) as the nucleophile and tetrabutylammonium tetrafluoroborate (19 mg, 0.057 mmol, 0.10 equiv.) as additive in acetonitrile (5.7 mL, 0.1 M) for 18 h at 25 °C. Purification by flash column chromatography on flash silica gel (0% ethyl-acetate in hexanes grading to 20% ethyl-acetate in hexanes) afforded the title compound 10 (90 mg, 0.37 mmol, 64%, 67% NMR yield). Physical State: colorless oil1H-NMR (499.64 MHz, CDCl3): δ = 4.03 (t, J = 6.8 Hz, 2H), 3.64 (s, 3H), 2.28 (t, J = 7.5 Hz, 2H), 2.02 (s, 3H), 1.64 – 1.53 (m, 4H), 1.35 – 1.24 ppm (m, 10H).13C-NMR (125.65 MHz, CDCl3): δ = 174.2, 171.1, 64.5, 51.3, 34.0, 29.2, 29.10, 29.08, 29.0, 28.5, 25.8, 24.9, 20.9 ppm. HRMS (ESI): [M+H]+calcd. for [C13H25O4]+245.1747, found 245.1745 TLC: Rf = 0.38 (13% ethyl-acetate in hexanes, KMnO4) Compound 11 (methyl 10-phenoxydecanoate) Following General Procedure with the following modifications: carried out on a 0.60 mmol scale using phenol (283 mg, 3.00 mmol, 5.00 equiv.) as the nucleophile and sodium carbonate (319 mg, 3.00 mmol, 5.00 equiv.) as the base in acetonitrile (6.0 mL, 0.1 M) for 18 h at 70 °C. Purification by flash column chromatography on flash silica gel (0% ethyl-acetate in hexanes grading to 20 % ethyl-acetate in hexanes) afforded the title compound 11 (79 mg, 0.28 mmol, 47%, 64% NMR yield). Physical State: colorless oil1H-NMR (499.64 MHz, CDCl3): δ = 7.30 – 7.25 (m, 2H), 6.95 – 6.88 (m, 3H), 3.95 (t, J = 6.6 Hz, 2H), 3.67 (s, 3H), 2.31 (t, J = 7.5 Hz, 2H), 1.82 – 1.73 (m, 2H), 1.63 (p, J = 7.1 Hz, 2H), 1.45 (td, J = 8.8, 4.8 Hz, 2H), 1.32 ppm (q, J = 4.3 Hz, 8H).13C-NMR (125.65 MHz, CDCl3): δ = 174.2, 159.1, 129.3, 120.4, 114.5, 67.8, 51.4, 34.1, 29.31, 29.27, 29.26, 29.14, 29.09, 26.0, 24.9 ppm. HRMS (ESI): [M+H]+calcd. for [C17H27O3]+279.1955, found 279.1949 TLC: Rf = 0.52 (10% ethyl-acetate in n-hexanes, KMnO4) Compound 12 ((10-methoxy-10-oxodecyl)triphenylphosphonium tetrafluoroborate) Following General Procedure with the following modifications: carried out on a 0.50 mmol scale using triphenylphosphine (393 mg, 1.50 mmol, 3.00 equiv.) as the nucleophile in acetonitrile (5.0 mL, 0.1 M) for 6 h at 70 °C. The reaction mixture was directly concentrated under reduced pressure and no aqueous workup was carried out. Purification by precipitation with the mixture of diethyl-ether and dichloromethane (20:1, 10 mL) afforded the title compound 12 (220 mg, 0.412 mmol, 82%). Physical State: pale brown solid1H-NMR (499.64 MHz, CDCl3): δ = 7.79 (tt, J = 5.7, 2.8 Hz, 3H), 7.73 – 7.67 (m, 12H), 3.63 (s, 3H), 3.28 – 3.19 (m, 2H), 2.26 (t, J = 7.5 Hz, 2H), 1.64 – 1.50 (m, 6H), 1.29 – 1.16 (m, 10H) ppm.13C-NMR (125.65 MHz, CDCl3): δ = 174.3, 135.1 (d, J = 2.9 Hz), 133.4 (d, J = 10.0 Hz), 130.5 (d, J = 12.7 Hz), 118.1 (d, J = 85.9 Hz), 51.4, 34.0, 30.2 (d, J = 15.8 Hz), 29.0, 28.91, 28.88, 28.82, 24.81, 22.5 (d, J = 4.5 Hz), 22.0 ppm (d, J = 50.9 Hz).19F-NMR (282.21 MHz, CDCl3): δ = -152.30 (s), -152.35 ppm (s).31P-NMR (202.27 MHz, CDCl3): δ = 23.7 ppm (s). HRMS (ESI): M+calcd. for [C29H36O2P]+447.2447, found 447.2428 TLC: Rf = 0.71 (5% methanol in dichloromethane, CAM) Compound 13 (methyl 10-(phenylthio)decanoate) Following General Procedure with the following modifications: carried out on a 0.50 mmol scale using thiophenol (258 µl, 2.51 mmol, 5.00 equiv.) as the nucleophile and sodium carbonate (211 mg, 2.51 mmol, 5.00 equiv.) as the base in acetonitrile (5.0 mL, 0.1 M) for 18 h at 25 °C. Purification by flash column chromatography on flash silica gel (0% ethyl-acetate in hexanes grading to 5% ethyl-acetate in hexanes) afforded the title compound 13 (95 mg, 0.32 mmol, 64%, 68% NMR yield). Physical State: colorless oil1H-NMR (499.64 MHz, CDCl3): δ = 7.34 – 7.30 (m, 2H), 7.29 – 7.25 (m, 2H), 7.15 (ddt, J = 8.6, 7.7, 1.3 Hz, 1H), 3.66 (s, 3H), 2.95 – 2.87 (m, 2H), 2.30 (t, J = 7.5 Hz, 2H), 1.69 – 1.56 (m, 4H), 1.41 (p, J = 7.0 Hz, 2H), 1.35 – 1.24 ppm (m, 8H).13C-NMR (125.65 MHz, CDCl3): δ = 174.2, 137.0, 128.9, 128.8, 125.6, 51.4, 34.1, 33.6, 29.2, 29.11 (2C), 29.07, 29.0, 28.7, 24.9 ppm. HRMS (ESI): [M+H]+calcd. for [C17H27O2S]+295.1726, found 295.1721 TLC: Rf = 0.43 (10% ethyl-acetate in hexanes, KMnO4) Compound 14 (methyl 10-thiocyanatodecanoate) Following General Procedure with the following modifications: carried out on a 0.50 mmol scale using potassium thiocyanate (243 mg, 2.50 mmol, 5.00 equiv.) as the nucleophile in acetonitrile (5.0 mL, 0.1 M) for 18 h at 25 °C. Purification by flash column chromatography on flash silica gel (0% ethyl-acetate in hexanes grading to 15% ethyl-acetate in hexanes) afforded the title compound 14 (95 mg, 0.39 mmol, 78%). Physical State: colorless oil1H-NMR (499.64 MHz, CDCl3): δ = 3.65 (s, 3H), 2.93 (t, J = 7.3 Hz, 2H), 2.29 (t, J = 7.5 Hz, 2H), 1.81 (p, J = 7.3 Hz, 2H), 1.61 (p, J = 7.3 Hz, 2H), 1.42 (dd, J = 9.4, 5.6 Hz, 2H), 1.35 – 1.27 ppm (m, 8H).13C-NMR (125.65 MHz, CDCl3): δ = 174.2, 112.3, 51.4, 34.02, 34.00, 29.8, 29.1, 29.02, 28.98, 28.7, 27.9, 24.8 ppm. HRMS (ESI): [M+H]+calcd. for [C12H22NO2S]+244.1366, found 244.1377 TLC: Rf = 0.26 (13% ethyl-acetate in hexanes, KMnO4) Compound 15 (methyl 10-cyanodecanoate) Following General Procedure with the following modifications: carried out on a 0.58 mmol scale using potassium cyanide (190 mg, 2.92 mmol, 5.00 equiv.) as the nucleophile and tetrabutylammonium tetrafluoroborate (19 mg, 0.058 mmol, 0.10 equiv.) as the phase transfer catalyst in acetonitrile (5.8 mL, 0.1 M) for 18 h at 25 °C. After analysis by TLC or LC-MS indicated the completion of the reaction, a modified aqueous workup was carried out as follows: dichloromethane (50 mL) and saturated sodium bicarbonate solution (50 mL) were added to the reaction mixture. The phases were separated and the organic layer was washed with saturated sodium bicarbonate solution (4 x 50 mL). Purification by flash column chromatography on flash silica gel (0% ethyl-acetate in n- hexanes grading to 20 % ethyl-acetate in n-hexanes) afforded the title compound 15 (65 mg, 0.31 mmol, 53%, 67% NMR yield). Physical State: colorless oil1H-NMR (499.64 MHz, CDCl3): δ = 3.63 (s, 3H), 2.29 (dt, J = 16.1, 7.4 Hz, 4H), 1.61 (ddt, J = 16.6, 14.5, 7.2 Hz, 4H), 1.45 – 1.37 (m, 2H), 1.33 – 1.24 ppm (m, 8H).13C-NMR (125.65 MHz, CDCl3): δ = 174.1, 119.7, 51.3, 33.9, 29.0 (2C), 28.9, 28.6, 28.5, 25.3, 24.8, 17.0 ppm. HRMS (ESI): [M+Na]+calcd. for [C12H21NO2Na]+234.1465, found 234.1459 TLC: Rf = 0.21 (10% ethyl-acetate in hexanes, KMnO4) Compound 16 (methyl 10-bromodecanoate) Following General Procedure with the following modifications: carried out on a 0.44 mmol scale using tetrabutylammonium bromide (705 mg, 2.19 mmol, 5.00 equiv.) as the nucleophile in acetonitrile (4.4 mL, 0.1 M) for 18 h at 25 °C. Purification by flash column chromatography on flash silica gel (0% ethyl-acetate in hexanes grading to 20% ethyl-acetate in hexanes) afforded the title compound 16 (69 mg, 0.18 mmol, 59%, 65% NMR yield). Physical State: colorless oil1H-NMR (499.64 MHz, CDCl3): δ = 3.64 (s, 3H), 3.38 (t, J = 6.9 Hz, 2H), 2.28 (t, J = 7.5 Hz, 2H), 1.83 (dt, J = 14.5, 7.0 Hz, 2H), 1.60 (p, J = 7.1 Hz, 2H), 1.39 (q, J = 7.1 Hz, 2H), 1.33 – 1.24 ppm (m, 8H).13C-NMR (125.65 MHz, CDCl3): δ = 174.1, 51.3, 34.0, 33.8, 32.7, 29.14, 29.05, 29.0, 28.6, 28.1, 24.9 ppm. HRMS (ESI): [M+H]+calcd. for [C11H22BrO2]+265.0798, found 265.0793 TLC: Rf = 0.60 (10% ethyl-acetate in n-hexanes, KMnO4) Compound 17 (methyl 10-fluorodecanoate) Following General Procedure with the following modifications: carried out on a 0.47 mmol scale using tetrabutylammonium fluoride in tetrahydrofuran solution (1.0 M, 2.32 mmol, 2.32 mL, 5.00 equiv.) as the nucleophile in acetonitrile (4.7 mL, 0.1 M) for 18 h at 25 °C. Purification by flash column chromatography on flash silica gel (0% ethyl-acetate in hexanes grading to 20% ethyl-acetate in hexanes) afforded the title compound 17 (36 mg, 0.18 mmol, 38%, 49% NMR yield). Physical State: colorless oil1H-NMR (499.64 MHz, CDCl3): δ = 4.42 (dt, J = 47.4, 6.2 Hz, 2H), 3.66 (s, 3H), 2.30 (t, J = 7.6 Hz, 2H), 1.74 – 1.57 (m, 4H), 1.42 – 1.34 (m, 2H), 1.34 – 1.26 ppm (m, 8H).13C-NMR (125.65 MHz, CDCl3): δ = 174.2, 84.2 (d, J = 164.0 Hz), 51.4, 34.1, 30.4 (d, J = 19.6 Hz), 29.3, 29.13, 29.10, 29.07, 25.1 (d, J = 5.4 Hz), 24.9 ppm.19F-NMR (282.21 MHz, CDCl3): δ = -218.08 ppm (tt, J = 47.3, 24.9 Hz). HRMS (ESI): [M+Na]+calcd. for [C11H21FO2Na]+227.1418, found 227.1413 TLC: Rf = 0.46 (13% ethyl-acetate in hexanes, KMnO4) Compound 18 (methyl 10-(pyridin-2-yloxy)decanoate) Following General Procedure with the following modifications: carried out on a 0.59 mmol scale using 2- pyridone (281 mg, 2.95 mmol, 5.00 equiv.) as the nucleophile and sodium carbonate (248 mg, 2.95 mmol, 5.00 equiv.) as the base in acetonitrile (5.9 mL, 0.1 M) for 18 h at 70 °C. Purification by flash column chromatography on flash silica gel (0% ethyl-acetate in hexanes grading to 25% ethyl-acetate in hexanes) afforded the title compound 18 (86 mg, 0.31 mmol, 52%, 55% NMR yield). Physical State: yellow oil1H-NMR (499.64 MHz, CDCl3): δ = 8.13 (ddd, J = 5.2, 2.0, 0.8 Hz, 1H), 7.54 (ddd, J = 8.8, 7.1, 2.0 Hz, 1H), 6.82 (ddd, J = 7.1, 5.0, 1.0 Hz, 1H), 6.71 (dt, J = 8.3, 0.9 Hz, 1H), 4.26 (t, J = 6.7 Hz, 2H), 3.65 (s, 3H), 2.29 (t, J = 7.5 Hz, 2H), 1.80 – 1.72 (m, 2H), 1.61 (p, J = 7.2 Hz, 2H), 1.43 (td, J = 8.6, 4.8 Hz, 2H), 1.37 – 1.28 ppm (m, 8H).13C-NMR (125.65 MHz, CDCl3): δ = 174.2, 164.1, 146.9, 138.4, 116.4, 111.0, 65.9, 51.4, 34.1, 29.33, 29.29, 29.15, 29.10, 29.0, 26.0, 24.9 ppm.15N-NMR (50.63 MHz, CDCl3): δ = -114.4 ppm HRMS (ESI): [M+H]+calcd. for [C16H26NO3]+280.1907, found 280.1898 TLC: Rf = 0.33 (13% ethyl-acetate in n-hexanes, KMnO4) Compound 19 (methyl 10-(pyridin-2-ylthio)decanoate) Following General Procedure with the following modifications: carried out on a 0.65 mmol scale using 2- mercaptopyridine (364 mg, 3.27 mmol, 5.00 equiv.) as the nucleophile and sodium carbonate (275 mg, 3.27 mmol, 5.00 equiv.) as the base in acetonitrile (6.5 mL, 0.1 M) for 18 h at 25 °C. Purification by flash column chromatography on flash silica gel (0% ethyl-acetate in hexanes grading to 25% ethyl-acetate in hexanes) afforded the title compound 19 (115 mg, 0.388 mmol, 59%, 63% NMR yield). Physical State: colorless oil1H-NMR (599.63 MHz, CDCl3): δ = 8.41 (dd, J = 4.2, 2.1 Hz, 1H), 7.46 (td, J = 7.7, 1.9 Hz, 1H), 7.16 (d, J = 8.1 Hz, 1H), 6.96 (dd, J = 7.3, 4.9 Hz, 1H), 3.66 (s, 3H), 3.15 (t, J = 7.4 Hz, 2H), 2.29 (t, J = 7.5 Hz, 2H), 1.69 (p, J = 7.4 Hz, 2H), 1.61 (p, J = 7.0 Hz, 2H), 1.43 (p, J = 7.0 Hz, 2H), 1.35 – 1.27 ppm (m, 8H).13C-NMR (150.79 MHz, CDCl3): δ = 174.3, 159.6, 149.3, 135.9, 122.2, 119.2, 51.4, 34.1, 30.1, 29.27, 29.26, 29.15, 29.09, 28.9, 24.9 ppm.15N-NMR (40.52 MHz, CDCl3): δ = -81.9 ppmHRMS (ESI): [M+H]+calcd. for [C16H26NO2S]+296.1679, found 296.1671 TLC: Rf = 0.71 (20% ethyl-acetate in n-hexanes, KMnO4) Compound 20a and 20b Following General Procedure with the following modifications: carried out on a 0.70 mmol scale using benzenesulfinic acid sodium salt (582 mg, 3.48 mmol, 5.00 equiv.) as the nucleophile and tetrabutylammonium tetrafluoroborate (23 mg, 0.070 mmol, 0.10 equiv.) as the phase transfer catalyst in acetonitrile (7.0 mL, 0.1 M) for 18 h at 70 °C. Purification by flash column chromatography on flash silica gel (0% ethyl-acetate in hexanes grading to 20 % ethyl-acetate in hexanes) afforded the title compound 20a and 20b (155 mg, 0.475 mmol, 68%, 70% NMR yield 20a:20b ratio = 1:1). Physical State: colorless oil 20a (methyl 10-((phenylsulfinyl)oxy)decanoate)1H-NMR (399.87 MHz, CDCl3): δ = 7.73 – 7.68 (m, 2H), 7.54 (dd, J = 5.1, 2.0 Hz, 3H), 4.03 (dt, J = 9.9, 6.7 Hz, 1H), 3.66 (s, 3H), 3.60 (dt, J = 9.9, 6.6 Hz, 1H), 2.29 (t, J = 7.5 Hz, 2H), 1.65 – 1.57 (m, 4H), 1.34 – 1.21 ppm (m, 10H).13C-NMR (100.56 MHz, CDCl3): δ = 174.3, 144.8, 132.0, 129.0, 125.2, 64.8, 51.4, 34.1, 29.6, 29.2, 29.09, 29.05, 29.00, 25.6, 24.9. HRMS (ESI): [M+H]+calcd. for [C17H27O4S]+327.1625, found 327.1625 20b (methyl 10-(phenylsulfonyl)decanoate)1H-NMR (499.64 MHz, CDCl3): δ = 7.93 – 7.88 (m, 2H), 7.68 – 7.62 (m, 1H), 7.59 – 7.53 (m, 2H), 3.65 (s, 3H), 3.11 – 3.02 (m, 2H), 2.27 (t, J = 7.5 Hz, 2H), 1.69 (tt, J = 7.9, 6.5 Hz, 2H), 1.58 (p, J = 7.4 Hz, 2H), 1.33 (t, J = 7.4 Hz, 2H), 1.30 – 1.20 ppm (m, 8H).13C-NMR (125.65 MHz, CDCl3): δ = 174.1, 139.2, 133.5, 129.1, 127.9, 56.2, 51.3, 33.9, 28.92, 28.88, 28.87, 28.78, 28.1, 24.8, 22.5 ppm. HRMS (ESI): [M+H]+calcd. for [C17H27O4S]+327.1625, found 327.1632 TLC: 20a: Rf = 0.15 (13% ethyl-acetate in n-hexanes, KMnO4) 20b: Rf = 0.33 (25% ethyl-acetate in n-hexanes, KMnO4) Compound 21 (methyl 10-oxodecanoate) Following General Procedure with the following modifications: carried out on a 0.50 mmol scale using 4- Methylmorpholine-N-oxide (293 mg, 2.50 mmol, 5.00 equiv.) as the nucleophile and sodium bicarbonate (210 mg, 2.50 mmol, 5.00 equiv.) as the base in acetonitrile (5.0 mL, 0.1 M) for 18 h at 50 °C. Purification by flash column chromatography on flash silica gel (0% ethyl-acetate in hexanes grading to 20% ethyl-acetate in hexanes) afforded the title compound 21 (51 mg, 0.25 mmol, 51%, 69% NMR yield). Physical State: colorless oil1H-NMR (499.64 MHz, CDCl3): δ = 9.74 (t, J = 1.9 Hz, 1H), 3.64 (s, 3H), 2.39 (td, J = 7.3, 1.8 Hz, 2H), 2.28 (t, J = 7.5 Hz, 2H), 1.60 (dq, J = 11.1, 3.7 Hz, 4H), 1.29 ppm (d, J = 4.1 Hz, 8H).13C-NMR (125.65 MHz, CDCl3): δ = 202.7, 174.2, 51.4, 43.8, 34.0, 29.1, 29.02, 28.98, 28.86, 24.8, 22.0 ppm. HRMS (ESI): [M+H]+calcd. for [C11H21O3]+201.1485, found 201.1481 TLC: Rf = 0.23 (20% ethyl-acetate in hexanes, KMnO4) Compound 24 (methyl decanoate-10-d) Following General Procedure with the following modifications: carried out on a 0.50 mmol scale using sodium tetrahydroborate-d4 (20.9 mg, 0.50 mmol, 1.00 equiv.) as the nucleophile for 6 h at 25 °C. Purification by flash column chromatography on flash silica gel (0% ethyl-acetate in hexanes grading to 20% ethyl-acetate in hexanes) afforded the title compound 24 (59.0 mg, 0.315 mmol, 63%). Physical State: colorless oil1H-NMR (499.64 MHz, CDCl3): δ = 3.65 (s, 3H), 2.29 (t, J = 7.5 Hz, 2H), 1.65 – 1.55 (m, 2H), 1.34 – 1.19 (m, 12H), 0.89 – 0.81 ppm (m, 2H).13C-NMR (125.65 MHz, CDCl3): δ = 174.3, 51.3, 34.1, 31.8, 29.4, 29.2, 29.1, 25.0, 22.5, 13.74 (t, J = 19.1 Hz) ppm. HRMS (ESI): [M+H]+calcd. for [C11H22DO2]+188.1755, found 188.1751 TLC: Rf = 0.55 (5% ethyl-acetate in hexanes, KMnO4) Specific procedures Compound 23 (methyl decanoate) A suspension of the 2f alkenyl thianthren-5-ium salt (243 mg, 0.500 mmol, 1 equiv.) and sodium bicarbonate (210 mg, 2.50 mmol, 5.00 equiv.) in anhydrous acetonitrile (5.0 mL, 0.1 M) were cooled to 0 °C under argon atmosphere. Then sodium borohydride (37.8 mg, 1.00 mmol mmol, 2.00 equiv.) was added in one portion at this temperature. After stirring the reaction mixture for 30 min, the mixture was warmed to 25 °C and stirred at this temperature for an additional 6 h, when analysis by LC-MS indicated full conversion. Then, saturated aqueous sodium bicarbonate solution (30 ml) and diethyl ether (30 mL) were added to the reaction mixture. The phases were separated and the aqueous layer was extracted with diethyl ether (30 mL). The combined organic layers were dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (0% ethyl-acetate in hexanes grading to 20% ethyl-acetate in hexanes) to afford the pure product 23 (56.3 mg, 0.302 mmol, 60%, 64% NMR yield). Physical State: colorless oil1H-NMR (499.64 MHz, CDCl3): δ = 3.65 (s, 3H), 2.29 (t, J = 7.6 Hz, 2H), 1.61 (p, J = 7.4 Hz, 2H), 1.33 – 1.18 (m, 12H), 0.87 ppm (t, J = 6.9 Hz, 3H).13C-NMR (125.65 MHz, CDCl3): δ = 174.3, 51.3, 34.1, 31.8, 29.4, 29.23, 29.22, 29.1, 24.9, 22.6, 14.0 ppm. HRMS (ESI): [M+H]+calcd. for [C11H23O2]+187.1693, found 187.1689 TLC: Rf = 0.55 (5% ethyl-acetate in hexanes, KMnO4) Compound 25- (methyl decanoate-9,10-d2) A suspension of the 2f alkenyl thianthren-5-ium salt (304 mg, 0.626 mmol, 1 equiv.) and sodium bicarbonate (263 mg, 3.13 mmol, 5.00 equiv.) in anhydrous acetonitrile (5.5 mL, 0.1 M) were cooled to 0 °C under argon atmosphere. Then sodium borohydride-d4 (52.4 mg, 1.25 mmol, 2.00 equiv.) was added in one portion at this temperature. After stirring the reaction mixture for 30 min, the mixture was warmed to 25 °C and stirred at this temperature for an additional 6 h, when analysis by LC-MS indicated full conversion. Then, saturated aqueous sodium bicarbonate solution (30 ml) and diethyl ether (30 mL) were added to the reaction mixture. The phases were separated and the aqueous layer was extracted with diethyl ether (30 mL). The combined organic layers were dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (0% ethyl-acetate in hexanes grading to 20% ethyl-acetate in hexanes) to afford the pure product 25 (79 mg, 0.42 mmol, 67%, 87% NMR yield). Physical State: colorless oil1H-NMR (499.64 MHz, CDCl3): δ = 3.67 (s, 3H), 2.30 (t, J = 7.6 Hz, 2H), 1.62 (h, J = 6.4 Hz, 2H), 1.36 – 1.18 (m, 11H), 0.85 ppm (dt, J = 4.8, 2.4 Hz, 2H).13C-NMR (125.65 MHz, CDCl3): δ = 174.3, 51.3, 34.1, 31.7, 29.43, 29.23, 29.20, 29.1, 24.9, 22.1 (t, J = 19.0 Hz), 13.6 ppm (t, J = 19.0 Hz). HRMS (ESI): [M+H]+calcd. for [C11H21D2O2]+189.1818, found 189.1814 TLC: Rf = 0.55 (5% ethyl-acetate in hexanes, KMnO4) Compound 22 (oxacyclododecan-2-one) Alkenyl thianthrene-5-ium salt was prepared from undec-10-enoic acid using literature known procedures. (1.24 g, 81% yield). (ref 18) A suspension of alkenyl thianthren-5-ium salt (243 mg, 0.500 mmol, 1 equiv.) and sodium bicarbonate (210 mg, 2.50 mmol, 5.00 equiv.) in anhydrous acetonitrile (5.0 mL, 0.1 M) was cooled to 0 °C under argon atmosphere. At this temperature well powdered sodium borohydride (13.2 mg, 0.70 mmol, 0.70 equiv.) was added in one portion. After stirring 60 min when analysis by LC-MS indicated full conversion, a mixture of HBF4.OEt2(0.5 mL) and saturated aqueous NaBF4(20 mL) and dichloromethane (20 mL) were subsequently added to the mixture. The layers were separated, and the organic phase was dried over sodium sulfate. The dried solution was filtered, and the filtrate was concentrated under reduced pressure to yield the crude 22b alkyl thiantren-5-ium tetrafluoroborate salt. A suspension of potassium carbonate (207 mg, 1.50 mmol, 3 equiv.) in anhydrous acetonitrile (500 mL) was heated under reflux under argon atmosphere. At this temperature, the crude 22b alkyl thianthrene-5-ium salt in acetonitrile (15 mL) was added dropwise via syringe pump over 24 h. Then, after stirring for an additional 24 h at this temperature, the suspension was cooled to ambient temperature and filtered. The filtrate was concentrated under reduced pressure to yield the crude macrocycle 22c. The residue was purified by flash column chromatography on silica gel (gradient elution from hexanes to 20% ethyl acetate in hexanes) to yield the pure macrocycle 22c (28.5 mg, 0.155 mmol, 25% over 3 steps from alkene, 31% NMR yield). Physical State: colorless oil1H-NMR (499.64 MHz, CDCl3): δ = 4.22 – 4.16 (m, 2H), 2.40 – 2.32 (m, 2H), 1.75 – 1.69 (m, 2H), 1.66 (qd, J = 6.4, 4.6 Hz, 2H), 1.53 (dq, J = 7.3, 6.2 Hz, 2H), 1.44 – 1.29 ppm (m, 10H).13C-NMR (125.65 MHz, CDCl3): δ = 173.9, 64.6, 34.4, 26.1, 24.89, 24.88, 24.5, 24.1, 23.9, 23.5, 23.3 ppm. TLC: Rf = 0.30 (5% ethyl-acetate in n-hexanes, KMnO4) Applications and one-pot modifications (EXAMPLES 3, 4) EXAMPLE 3 Applications and one-pot modifications Compound 23 (methyl decanoate) General: All electrochemical oxidations were carried out using an IKA ElectraSyn 2.0 potentiostat (Ident. No. 0020008980, IKA), equipped with an IKA Pro-Divide divided cell (Ident. No.0040006482, IKA) with a 10 µm frit, and standard IKA electrodes (RVC: Ident. No.0040002860, IKA; Nickel foam: Ident. No.0040002861, IKA). Tetrafluoroboric acid diethyl ether complex (1.62 g, 1.36 mL, 10.0 mmol, 5 equiv.) was added to a solution of tetra-n-butylammonium tetrafluoroborate (527 mg, 1.60 mmol, 0.8 equiv.) in anhydrous acetonitrile (5 mL). This solution was transferred to the cathodic compartment of an IKA Pro-Divide divided electrochemical cell equipped with magnetic stirring bars. Next, 23a, methyl dec-9-enoate (9-DAME, 369 mg, 2.00 mmol, 1 equiv.) was added to a separate solution of tetra-n-butylammonium tetrafluoroborate (527 mg, 1.60 mmol, 0.8 equiv.) in anhydrous acetonitrile (5 mL). This solution in turn was transferred to the anodic compartment of the electrochemical cell. Finally, under stirring, thianthrene (TT, 649 mg, 3.00 mmol, 1.5 equiv.) was added to the anodic compartment [Note 1]. The closing cap of the cell was equipped with a standard IKA RVC anode and a standard IKA nickel foam cathode, and the cell was sealed. Both compartments were flushed with argon gas through the septa on the top of the cell, after which argon-filled balloons were inserted into them. The cell was inserted into the IKA ElectraSyn 2.0 potentiostat and the reaction mixture was electrolyzed at a constant current of 45 mA for 3.5 F / mol of alkene, with stirring set to 400 RPM [Note 2]. Complete conversion of the alkene was achieved based on TLC measurement. Next, the cell was opened, and the lilac anodic solution was transferred into a 50 mL flask. The RVC anode and the anodic compartment were further washed with 5 mL anhydrous acetonitrile into the flask. At this point, solid sodium bicarbonate (6.72 g, 80.0 mmol, 8.00 equiv.) was added in one portion, and the two-phase mixture was vigorously stirred at 25 °C for 3 min, whereupon an immediate color change to yellow was observed. Then, the two-phase mixture was cooled to 2 °C with an ice bath and sodium borohydride (1.89 g, 50.0 mmol, 5.00 equiv.) was added in small portions, whereupon the temperature began to raise. [Note 5] The cooling was maintained for 5 min. [Note 6] then it was left to warm to 25 °C and stirred at this temperature for 4 h until analysis by LCMS indicated full conversion. Then, saturated aqueous sodium bicarbonate solution (120 ml) and diethyl ether (120 mL) were added to the reaction mixture. The phases were separated and the aqueous layer was extracted with diethyl ether (3x120 mL). The combined organic layers were dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product 23 (12% NMR yield). [Note 1]: As the solubility of thianthrene is low in acetonitrile, complete dissolution of the solids will take place only as the electrochemical reaction consumes the thianthrene. Intensive stirring is needed to suspend the thianthrene so that the stirring bars of the Pro-Divide cell don’t get stuck in the solid material. [Note 2]: The IKA ElectraSyn was set up as follows: New experiments → Constant current → 45 mA → No reference electrode → Total charge → 2.0 mmol, 3.5 F / mol → No alternating polarity → Start → 400 RPM stirring Scale up, one pot thianthrenation / reduction (EXAMPLE 4) II. Scale up, one pot thianthrenation / reduction- Compound 27 (4-ethyl-1-tosylpiperidine) A suspension of alkene 26 (2.65 g, 10.0 mmol, 1 equiv.) and thianthrene (2.49 g, 11.5 mmol, 1.15 equiv.) in anhydrous acetonitrile (100 mL, 0.1 M) was cooled to 2 °C (internal temperature) under argon atmosphere. [Note 1] At this temperature, 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) ( 8.15 g, 23.0 mmol, 2.30 equiv.) was added in one portion. [Note 2, 3] A delayed color change of the reaction mixture to dark purble was observed within ca. 1 min. Then, boron trifluoride diethyl etherate (2.92 mL, 23.00 mmol, 2.30 equiv.) was added dropwise over ca. 3 min while maintaining the internal temperature below 5 °C. [Note 4] The color of the reaction mixture turned dark blue upon addition. The reaction mixture was stirred at this temperature while maintaining cooling for 10 min. Then, the reaction mixture was warmed to 25 °C over 30 min and stirred at this temperature for an additional 2 h until analysis by TLC indicated full conversion and a slight color change to purple was observed. At this point, solid sodium bicarbonate (6.72 g, 80.0 mmol, 8.00 equiv.) was added in one portion, and the two-phase mixture was vigorously stirred at 25 °C for 3 min, whereupon an immediate color change to yellow was observed. Then, the two-phase mixture was cooled to 2 °C with an ice bath and sodium borohydride (1.89 g, 50.0 mmol, 5.00 equiv.) was added in small portions, whereupon the temperature began to raise. [Note 5] The cooling was maintained for 5 min. [Note 6] then it was left to warm to 25 °C and stirred at this temperature for 4 h until analysis by LC-MS indicated full conversion. Saturated aqueous sodium bicarbonate solution (200 mL) and dichloromethane (200 mL) were added subsequently. The layers were separated, and the aqueous phase was extracted with dichloromethane (200 mL). The combined organic layers were washed with a mixture of brine (200 mL) and water (200 mL) and dried over sodium sulfate. The dried solution was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (gradient elution from hexanes to 30% ethyl acetate in hexanes) to yield 27 as a colorless oil which solidified upon standing (2.02 g, 7.55 mmol, 76%). [Note 1]: An ice bath was used. [Note 2]: The reagent was grounded prior to use. [Note 3]: The addition is almost thermoneutral. [Note 4]: The addition is slightly exothermic. [Note 5]: CAUTION! Extensive gas evolution is observed! [Note 6]: The temperature raised until 15 °C. [Note 7]: The temperature may raise above room temperature (25 °C in this case) and was only controlled if it reached 30 °C. Physical State: white solid1H-NMR (499.64 MHz, CDCl3): δ = 7.62 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 3.74 (dt, J = 11.6, 2.6 Hz, 2H), 2.41 (s, 3H), 2.21 (td, J = 12.0, 2.6 Hz, 2H), 1.70 (dd, J = 13.7, 2.6 Hz, 2H), 1.30 – 1.18 (m, 4H), 1.05 (m, 1H), 0.82 (t, J = 7.4 Hz, 3H).13C-NMR (125.65 MHz, CDCl3): δ = 143.4, 133.5, 129.6, 127.8, 46.6, 36.9, 31.3, 28.8, 21.6, 11.2 ppm. HRMS (ESI): [M+H]+calcd. for [C14H22NO2S]+268.1366, found 268.1358 TLC: Rf = 0.31 (10% ethyl-acetate in n-hexanes, KMnO4) Synthesis of alkenyl thianthrenium salts (EXAMPLE 11) All alkenyl thianthrenium salts used were prepared either by the use of the combination of thianthrenium-S-oxide, trifluoroacetic anyhdride and trifluoromethanesulfonic acid or thianthrenium-S-oxide and trifluoromethanesulfonic acid as described by ref. 19, or by using the combination of thianthrene, a fluorinating agent (i.e.1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)) and a Lewis acid (i.e. boron trifluoride diethyl etherate) as described herein by a representative procedure: A suspension of alkene 28 (230 mg, 1 mmol, 1.00 equiv) and thianthrene (282 mg, 1.30 mmol, 1.30 equiv.) in anhydrous acetonitrile (8.7 mL, 0.1 M) was cooled to 0 °C with an ice water bath under argon atmosphere. At this temperature, 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (711 mg, 2.01 mmol, 2.00 equiv.) was added in one portion. A delayed color change of the reaction mixture to dark purple was observed within ca. 1 min. Then, boron trifluoride diethyl etherate (248 µL, 2.01 mmol, 2.00 equiv.) was added dropwise. The color of the reaction mixture turned dark blue upon addition. The reaction mixture was stirred at this temperature while maintaining cooling for 30 min. Then, the reaction mixture was warmed to 25 °C and stirred at this temperature for an additional 1 h when analysis by TLC indicated full conversion. At this point the mixture was diluted with dichloromethane (40 mL) and sat. aq. sodium bicarbonate solution was added in one portion (40 mL). The layers were separated, and the organic phase was dried over sodium sulfate. The dried solution was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by trituration using diethyl ether and dichloromethane (11 ml, V / V = 10:1) [Note1] to yield 1i (464 mg, 0.87 mmol, 87%) alkenyl- thianthren-5-ium salt. [Note1]: An ultrasonic bath was used in case of performing a trituration or precipitation. Spectral and physical properties were in accordance with those reported in the literature. (Ref 14a, Ref 18, Ref 37) The same procedure was carried out by changing the boron trifluoride etherate to lithium tetrafluoroborate (164 mg, 1.74 mmol, 2.00 eq.; NMR yield: 47%) or trimethylsilyl trifluoromethanesulfonate (322 µL, 1.74 mmol, 2.00 eq.; NMR yield: 64%) with the formation of the corresponding alkenyl thianthrenium tetrafluoroborate or alkenyl thianthrenium triflate salt. The representative procedure using boron trifluoride diethyl etherate (detailed above) was used to synthesize the following alkenyl thianthrenium salts from the corresponding alkenes. Spectral and physical properties were in accordance with those reported in the literature. (Ref 14a,Ref18,Ref37)

[0004] Compound 1ll (5-(6-bromohex-1-en-1-yl)-5H-thianthren-5-ium tetrafluoroborate) Physical State: brown oil1H-NMR (499.64 MHz, DMSO-d6): δ = 8.27 (dd, J = 8.0, 1.4 Hz, 2H), 8.06 (dd, J = 7.8, 1.3 Hz, 2H), 7.86 (td, J = 7.7, 1.4 Hz, 2H), 7.77 (td, J = 7.7, 1.3 Hz, 2H), 6.86 – 6.74 (m, 2H), 3.47 (t, J = 6.7 Hz, 2H), 2.29 (td, J = 7.4, 5.4 Hz, 2H), 1.73 (dt, J = 14.3, 6.8 Hz, 2H), 1.48 ppm (p, J = 7.4 Hz, 2H).13C-NMR (125.65 MHz, DMSO-d6): δ = 153.5, 134.4, 134.1, 133.4, 130.0, 129.6, 120.8, 111.6, 34.4, 31.3, 31.1, 25.5 ppm.19F-NMR (282.21 MHz, DMSO-d6): δ = -144.87 (s), -144.93 ppm (s). HRMS (ESI): M+calcd. for [C18H18BrS2]+377.0028, found 377.0013 References: 1) C. Chen, M. Wang, H. Lu, B. Zhao, Z. Shi, Angew. Chem. Int. Ed Engl.2021, 60, 21756–21760. 2) C. Chen, Z.-J. Wang, H. Lu, Y. Zhao, Z. Shi, Nat. Commun.2021, 12, 4526.; F.-S. He, P. Bao, Z. Tang, F. Yu, W.-P. Deng, J. Wu, Org. Lett. 2022, 24, 2955–2960.; X. Li, W. Si, Z. Liu, H. Qian, T. Wang, S. Leng, J. Sun, Y. Jiao, X. 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Claims

Claims 1. Method for preparing alkyl sulfonium salts according to Formula I:wherein R1 and R2, independently from each other, are H; C1-C20 alkyl, preferably C1-C14 alkyl; C2-C20 alkenyl, preferably C2-C14 alkenyl; C2-C20 alkynyl, preferably C2-C14 alkynyl; -O-C1-C20 alkyl, preferably - O-C1-C14 alkyl; -O-C2-C20 alkenyl; -O-C2-C20 alkynyl; C3-C10 cycloalkyl; 4-10-membered heterocycloalkyl containing one or more heteroatoms independently selected from N, O and S; C6-C14 aryl, preferably phenyl; or 5-10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S; wherein each alkyl, alkenyl, and alkynyl can be straight chained or branched, and each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, heteroaryl and aryl can be substituted with 1-3 substituents independently selected from halogen, -CN, -OH, -OR25, -OTs, -OMs, -O-C(O)R21, -O-C1-C6 alkyl, -COOH, -C(O)-OR22, 1,3-dioxoisoindolin-2-yl, -NH-C(O)-C1-C6 alkyl, - N(C1-C6 alkyl)-C(O)-C1-C6 alkyl, -NHR23, -N(C1-C6 alkyl)R23, -C(O)-NH-C1-C6 alkyl, - C(O)-N(C1-C6 alkyl)2, C3-C10 cycloalkyl, 4-10-membered heterocycloalkyl containing one or more groups independently selected from –NR23-, -O- or –S-, C6-C10 aryl, 5-10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S; or R1 and R2 together with the carbon atom to which they are attached may form a saturated 5-6 membered cycloalkyl or heteroaryl or aryl; which can be substituted with 1-3 substituents independently selected from halogen, -CN, -OH, -OR25, -OTs, -OMs, -O-C(O)R21, -O-C1-C6 alkyl, -COOH, -C(O)-OR22, 1,3- dioxoisoindolin-2-yl, -NH-C(O)-C1-C6 alkyl, -N(C1-C6 alkyl)-C(O)-C1-C6 alkyl, -NHR23, -N(C1-C6 alkyl)R23, -C(O)-NH-C1-C6 alkyl, -C(O)-N(C1-C6 alkyl)2, C3-C10 cycloalkyl, 4-10-membered heterocycloalkyl containing one or more groups independently selected from –NR23-, -O- or –S-, C6-C10 aryl, 5-10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S or R1 and R4 together with the carbon atoms to which they are attached may form a partially unsaturated 5- 15-membered, preferably 5-8-membered cycloalkyl; or R1 and R4 may form a chain having 2-5 chain atoms and comprises CH2 units and / or 1-2 heteroatoms selected from N, O and S; R3 is H, C1-C4 alkyl, C6-C10 aryl, 4-methyltetrahydro-2H-pyran-2-yl; with the proviso that R1 is other than H when all R2-R4 are H R4 is H, C1-C4 alkyl, 4-methyltetrahydro-2H-pyran-2-yl; or together with R1, R4 may form cycloalkyl or chain as described above; R21 is H; C1-C4 alkyl; or C6-C10 aryl, preferably phenyl; R22 is C1-C4 alkyl, C2-C4 alkenyl or C2-C4 alkynyl;R23 is N-protecting group; R25 is O-protecting group; R5 and R6 are selected from C1-C6 alkyl, C5-C7 cycloalkyl, C6-C10 aryl, wherein each of alkyl, cycloalkyl and aryl can be substituted with one or more substituents independently selected from halogen, C1-C2 alkyl, preferably R5 and R6 are C6-C10 aryl, more preferably both aryl has at least one substituent in ortho position and said substituents of the aryls (R5 and R6) may form a direct bond between the aryls or a chain comprising CH2 units and / or a heteroatom (preferably selected from N, O and S, more preferably S), more preferably R5 and R6 are both an optionally substituted phenyl even more preferably the SR5R6 moiety isX- is a counter anion, preferably TfO-, MsO-, TsO-, TFA-, BF4-, PF6-, ClO4- , more preferably BF4- wherein the methods include the following step: (i) reacting an alkenyl sulfonium salt of Formula III-1III-1 or a synthetic equivalent product thereof including an allyl-sulfonium of Formula III-2 III-3III-3or a dicationic adduct of Formula III-4, III-4 or a mixture thereof; after reacting them first with a base to produce III-1; wherein X- and R1-R6 has the meaning as described above, both R7 is ortho-phenylene which is optionally substituted as described above at R5 and R6; with a hydride source, preferably a borane or borohydride or aluminium hydride or silane according to Formula IIIa or IIIb or IIIc or IIId or IIIe:IIIa IIIb IIIc IIId IIIe wherein, An+is a metal cation, such as Li+, Na+, Mg2+, Al3+, Ca2+, Zn2+, Ce3+, or tetrasubstituted ammonium ions, for example NH4+, NnBu4+. Y1 to Y5 are substituents that may be the same or different and selected from hydride, acetoxy-, cyano-, or a C1-C6 alkyl, or Y1 and Y2 or Y4 and Y5 together with the boron atom to which they are attached may form a saturated 5-9 membered cycloalkyl ring; (e.g., 9-borabicyclo[3.3.1]nonane) Z1 to Z5 are substituents that may be the same or different and selected from hydride, acetoxy-, cyano-, or a C1-C6 alkyl, bis(2-methoxyethoxy); Z6 to Z8 are substituents that may be the same or different and selected from hydride, C1-C6 alkyl, or phenyl; preferably, Formula IIIa is sodium borohydride, lithium borohydride, sodium cyanoborohydride, sodium acetoxyborohydride, lithium triethylborohydride, or deuterium / tritium labelled version thereof even more preferably Formula IIIa is sodium borohydride or deuterium / tritium labelled version thereof; wherein, Formula IIIb is BH3optionally used in a form of a complex well known in the art (e.g., borane- THF complex, borane-Me2S complex) or 9-Borabicyclo[3.3.1]nonane;preferably, Formula IIIc is LiAlH4or Sodium bis(2-methoxyethoxy)aluminium hydride; preferably, Formula IIId is Diisobutylaluminium hydride; preferably, Formula IIIe is PhSiH3; preferably in the presence of an organic or inorganic proton source, more preferably in the presence of sodium bicarbonate, potassium bicarbonate, disodium phosphate, potassium bisulfate under conditions sufficient to form an alkyl sulfonium product according to Formula I.

2. Method according to claim 1, further comprising the steps of (i) forming a reaction mixture comprising: - an olefin according to Formula II:wherein R1-R4 have the meaning as described in point 1, - a sulfoxide or sulfide according to Formula IIa or IIb: , IIa IIb wherein R5 and R6 have the meaning as described in point 1, more preferably the compound of formula IIa isand even more preferably an optionally substitutedoptionally substituted TTO), and the optional substitution is a tetrafluoro substitution (i.e., formula IIa isand the compound of formula IIb isand even more preferably an optionally substitutedan optionally substituted TT), and the optional substitution is a tetrafluoro substitution (i.e., formula IIb is- an activating agent or oxidizing agent, preferably carboxylic acid anhydride in the presence of an acid or 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate), 1-Chloromethyl-4- fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(trifluoromethanesulfonate), 1-Chloromethyl-4-fluoro-1,4- diazoniabicyclo[2.2.2]octane bis(hexafluorophosphate), boron trifluoride, boron trifluoride etherate, trimethylsilyl trifluoromethanesulfonate, trifluoromethane sulfonic anhydride, or trifluoromethane sulfonic acid or methane sulfonic acid, optionally with trifluoroacetic anhydride or acetic anhydride, sodium tetrafluoroborate, tetra-n-butylammonium hexafluorophosphate, alkyl or aryl sulfonic acids, or combinations thereof, which might be replaced with an activating or oxidizing treatment (e.g., electrochemical oxidation), said agents and / or treatment provides X- which is preferably TfO-, MsO, TsO- , TFA-, BF4-, PF6-, ClO4-, preferably using 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) combined with boron trifluoride or boron trifluoride diethyl etherate or lithium tetrafluoroborate or trimethylsilyl trifluoromethanesulfonate and combinations thereof, even more preferably using 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) with boron trifluoride diethyl etherate; (ii) maintaining the reaction mixture under conditions sufficient to form an alkenyl sulfonium salt of Formula III- 1,III-1 or a synthetic equivalent product including an allyl-sulfonium of Formula III-2III-3 III-3 or a dicationic adduct of Formula III-4, if Formula IIa or IIb represent an optionally substituted TTO or TT, III-4 or a mixture thereof; wherein R7 and X- have the meaning as described above.

3. Method according to claim 1 or 2 for transforming the obtained alkyl sulfonium products according to Formula I, preferably without isolation, into anti-Markovnikov addition products of Formula Va or Vb or Vc or Vd by reacting them with a nucleophile:wherein Rm is -N3, -CN, -SCN -F, -Cl, -Br, -I, =O, -H, -D, -T; Q is N, N(CO)2, O, O(CO), O(SO), P, S, SO2; Rz, Ry, and Rx are independently moeties that do not influence the reactivity of Q, which takes part in the reaction; for example C1-C20 alkyl, preferably C1-C14 alkyl; C2-C20 alkenyl, preferably C2-C14alkenyl; C2-C20 alkynyl, preferably C2-C14 alkynyl; C3-C10 cycloalkyl; 4-10-membered heterocycloalkyl containing one or more heteroatoms independently selected from N, O and S; C6-C14 aryl, preferably phenyl; or 5-10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S, or two Ry together with Q, when Q is N atom, to which they are attached may form a saturated, partially unsaturated or aromatic 4-7 membered heterocyclyl, and substituted versions thereof with one or more substituents defined at R1 and R2 above X- has the meaning as described above; wherein the method includes: (i) forming a reaction mixture comprising: - an alkyl sulfonium salt according to Formula I, - a nucleophile, wherein the nucleophile is selected from Formula VIa or VIb or VIc or Vid VIa VIb VIc VId or an appropriate salt thereof, and - optionally an organic or inorganic base; (ii) maintaining the reaction mixture under conditions sufficient to form the product according to Formula Va or Vb or Vc or Vd.

4. Method according to any of claims 1-3, wherein R5 and R6 are C6-C10 aryl, which can be substituted with one or more substituents independently selected from halogen, C1-C2 alkyl, preferably R5 and R6 are both phenyl, more preferably having at least one substituent in ortho position and said substituents of the phenyls (R5 and R6) may form a direct bond between the phenyls or a chain comprising CH2 units and / or a heteroatom (preferably selected from N, O and S, more preferably S), more preferably the compound of formula IIa is ,and the compound of formula IIb is, and even more preferably5. Method for preparing an alkenyl sulfonium salt of Formula III-1,III-1 or a synthetic equivalent product including an allyl-sulfonium of Formula III-2 III-3III-3 or a dicationic adduct of Formula III-4,, III-4 or a mixture thereof;wherein the method comprises the following steps: (i) forming a reaction mixture comprising: - an olefin according to Formula II:wherein R1-R4 have the meaning as described in any of the preceeding claims, - sulfide according to Formula IIb: , IIb wherein R5 and R6 have the meaning as described in any of the previous claims, more preferably the compound of formula IIb isand even more preferably an optionally substitutedan optionally substituted TT), and the optional substitution is a tetrafluoro substitution (i.e., formula IIb isand activating agents (e.g., 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate), 1- Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(trifluoromethanesulfonate), 1-Chloromethyl-4- fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(hexafluorophosphate), N-chlorosucinimide, N-fluoro pyridine derivatives, N-fluorobenzenesulfonimide, N-fluoro-o-benzenedisulfonimide, trichloro isocyanuricacid), preferably electrophile fluorinating agents (e.g., 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate, 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(trifluoromethanesulfonate), 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(hexafluorophosphate)), N-fluoro pyridine derivatives, N-fluorobenzenesulfonimide, N-fluoro-o-benzenedisulfonimide)); even more preferably 1- Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate), in combination with a Lewis acidic additive (e.g., boron trifluoride, boron trifluoride etherate, trimethylsilyl trifluoromethanesulfonate, trispentafluorophenylborane, magnesium chloride, magnesium triflate); preferably trimethylsilyltrifluoromethanesulfonate, lithium tetrafluoroborate or boron trifluoride diethyl etherate; even more preferably boron trifluoride diethyl etherate. R1, R2, R3 and R4 are as described in claim 1. (ii) maintaining the reaction mixture under conditions sufficient to form an alkenyl sulfonium salt of Formula III- 1, or a synthetic equivalent product including an allyl-sulfonium of Formula III-2, or a bis-adduct of Formula III- 3, or a dicationic adduct of Formula III-4, or a mixture thereof; wherein R7 and X- have the meaning as described above.

6. Method according to any of claims 1 to 4, wherein the hydride source is selected from sodium borohydride, lithium borohydride, sodium cyanoborohydride, sodium acetoxyborohydride, Lithium tri-sec- butylborohydride, or deuterium / tritium labelled version thereof; and / or BH3or borane-THF complex, borane- Me2S complex or 9-Borabicyclo[3.3.1]nonane; and / or LiAlH4 or Sodium bis(2-methoxyethoxy)aluminium hydride; and / or Diisobutylaluminium hydride; and / or, manganese(III) (Z)-2,2,6,6-tetramethyl-5-oxohept-3-en-3- olate combined with phenylsilane,. preferably the reducing agent is sodium borohydride or deuterium / tritium labelled version thereof.

7. Method according to any of the preceeding claims, wherein R1 and R2, independently from each other, are H; C1-C14 alkyl; C2-C6 alkenyl; C2-C6 alkynyl; -O-C1-C6 alkyl; or phenyl; wherein each alkyl, alkenyl and alkynyl can be straight chain or branched, and each alkyl, alkenyl, alkynyl and aryl can be substituted with 1-3 substituents independently selected from halogen, -CN, -O-C(O)R21, -OC1-C4 alkyl, -COOH, -C(O)-OR22, 1,3- dioxoisoindolin-2-yl or phenyl; or R1 and R2 together with the carbon atom to which they are attached may form a saturated 5-6 membered cycloalkyl or heteroaryl or aryl, which can be substituted with 1-3 substituents independently selected from halogen, -CN, -OH, -OR25, -OTs, -OMs, -O-C(O)R21, -O-C1-C6 alkyl, -COOH, -C(O)-OR22, 1,3- dioxoisoindolin-2-yl, -NH-C(O)-C1-C6 alkyl, -N(C1-C6 alkyl)-C(O)-C1-C6 alkyl, -NHR23, -N(C1-C6 alkyl)R23, -C(O)-NH-C1-C6 alkyl, -C(O)-N(C1-C6 alkyl)2, C3-C10 cycloalkyl, 4-10-membered heterocycloalkyl containing one or more groups independently selected from –NR23-, -O- or –S-, C6-C10 aryl, 5-10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S or R1 and R4 together with the carbon atoms to which they are attached may form a partially unsaturated 5- 6 membered cycloalkyl; R3 is H; with the proviso that R1 is not H when R2 and R3 are both H R4 is H, C1-C4 alkyl, or together with R1, R4 may form cycloalkyl as described above; R21 is H; C1-C4 alkyl; or phenyl; R22 is C1-C4 alkyl, or C1-C4 alkynyl.

8. Method according to any of the preceeding claims, wherein R2 and R3 are H; or alternatively R3 and R4 are H; or alternatively R2, R3 and R4 are H.

9. Method according to any of the preceeding claims, wherein R1 is C1-C14 alkyl; which is optionally substituted, preferably with 1-3 substituents independently selected from halogen, -CN, -O-C(O)R21, -OC1-C4 alkyl, -COOH, -C(O)-OR22, 1,3-dioxoisoindolin-2-yl or phenyl.

10. Method according to any of the preceeding claims, wherein the alkyl thianthrenium according to Formula I is selected from: 5-butyl-5H-thianthren-5-ium tetrafluoroborate, 5-(2-cyclohexylethyl)-5H-thianthren- 5-ium tetrafluoroborate, 5-(3-phenylpropyl)-5H-thianthren-5-ium tetrafluoroborate, 5-(oct-5-en-1-yl)-5H- thianthren-5-ium tetrafluoroborate, 5-(5-oxo-5-(prop-2-yn-1-yloxy)undecyl)-5H-thianthren-5-ium tetrafluoroborate, 5-(10-methoxy-10-oxodecyl)-5H-thianthren-5-ium tetrafluoroborate, 5-(6-(benzoyloxy)hexyl)- 5H-thianthren-5-ium tetrafluoroborate, 5-(4-cyanopentyl)-5H-thianthren-5-ium tetrafluoroborate, 5-(6-(1,3- dioxoisoindolin-2-yl)hexyl)-5H-thianthren-5-ium tetrafluoroborate, 5-(3-(3-phenylpropoxy)propyl)-5H- thianthren-5-ium tetrafluoroborate, 5-(6-chlorohexyl)-5H-thianthren-5-ium tetrafluoroborate, 5-(6-bromohexyl)- 5H-thianthren-5-ium tetrafluoroborate, 5-(6-(1,3-dioxoisoindolin-2-yl)hexyl)-5H-thianthren-5-ium tetrafluoroborate, 5-cyclopentyl-5H-thianthren-5-ium tetrafluoroborate, 5-cyclohexyl-5H-thianthren-5-ium tetrafluoroborate, 5-(tetrahydro-2H-pyran-3-yl)-5H-thianthren-5-ium tetrafluoroborate, 5-(sec-butyl)-5H- thianthren-5-ium tetrafluoroborate, 5-(hexan-3-yl)-5H-thianthren-5-ium.

11. Method according to any of the preceeding claims, wherein the reaction is performed in non- nucleophilic or weakly-nucleophilic solvents or solvent mixtures selected from water, alcohols e.g., isopropanol; ethers e.g., glymes, tetrahydrofuran, methyltetrahydrofuran, diethyl ether, methyl tert-butyl ether, diisopropyl ether, dibuthyl ether or 1,4-dioxane; aliphatic hydrocarbons e.g., hexane, heptane, petroleum ether, octane, or cyclohexane; aromatic hydrocarbons e.g., benzene, toluene, xylene or mesitylene; halocarbons e.g., dichloromethane, chloroform, dichloroethane; and additional polar aprotic solvents e.g. acetonitrile, dimethylformamide, dimethyl sulfoxide; or a mixture thereof or deuterated versions thereof e.g., acetonitrile-d3; preferably acetonitrile; and / or wherein the reaction is performed at a temperature of -40°C to 80°C, preferably at a temperature within the range of 0 to 25 °C; and / or wherein the proton source is selected from sodium bicarbonate, potassium bicarbonate, disodium phosphate, potassium bisulfate, preferably sodium bicarbonate; and / or wherein equivalents of hydride source reagent to compound of III-1 – III-4 is in the range of 0.25 to 5 equiv, preferably within the range of 0.25 to 0.50 equiv, even more preferably 0.35 equiv.

12. Methods according to any of the preceeding claims, wherein the nucleophile is selected from primary amines, secondary amines, tertiary amines, phtalimides, azides, carboxylic acids, phenols, water, phosphines, thiols, thiocyanate, cyanide, bromide, fluoride, sulfinic acid, N-oxides, sulfoxides, hydrides (including deuterium / tritium labelled reagents.

13. Methods according to any of the preceeding claims, wherein the activating agent is selected from 1- Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate), 1-Chloromethyl-4-fluoro-1,4- diazoniabicyclo[2.2.2]octane bis(trifluoromethanesulfonate), 1-Chloromethyl-4-fluoro-1,4- diazoniabicyclo[2.2.2]octane bis(hexafluorophosphate), N-chlorosucinimide, N-fluoro pyridine derivatives, N- fluorobenzenesulfonimide, N-fluoro-o-benzenedisulfonimide, trichloro isocyanuricacid, electrophile fluorinatingagents e.g., 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate, 1-Chloromethyl-4- fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(trifluoromethanesulfonate), 1-Chloromethyl-4-fluoro-1,4- diazoniabicyclo[2.2.2]octane bis(hexafluorophosphate); N-fluoro pyridine derivatives, N- fluorobenzenesulfonimide, N-fluoro-o-benzenedisulfonimide); even more preferably 1-Chloromethyl-4-fluoro- 1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate), in combination with a Lewis acidic additive e.g., boron trifluoride, boron trifluoride etherate, trimethylsilyl trifluoromethanesulfonate, trispentafluorophenylborane, magnesium chloride, magnesium triflate; preferably trimethylsilyl trifluoromethanesulfonate, lithium tetrafluoroborate or boron trifluoride diethyl etherate; even more preferably boron trifluoride diethyl etherate.

14. Methods according to any of the preceeding claims, wherein the activating agent is selected from electrophile fluorinating agents e.g., 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate), 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(trifluoromethanesulfonate), 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(hexafluorophosphate), N-fluoro pyridine derivatives, N-fluorobenzenesulfonimide, N-fluoro-o-benzenedisulfonimide), preferably 1-Chloromethyl-4- fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate), in combination with boron trifluoride or boron trifluoride etherate or trimethylsilyl trifluoromethanesulfonate or lithium tetrafluoroborate, preferably trimethylsilyl trifluoromethanesulfonate, lithium tetrafluoroborate or boron trifluoride diethyl etherate; even more preferably boron trifluoride diethyl etherate.

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