HYDRATION OF ESTERS TO ALCOHOLS IN THE PRESENCE OF AN MN-PNN COMPLEX

Description

[0001] The present invention relates to a process for the hydrogenation of an ester with molecular hydrogen to the corresponding alcohols in the presence of a manganese complex with a tridentate PNN ligand.

[0002] Alcohols are not only important solvents, but also important intermediates and synthetic building blocks, for example, in the production of pharmaceuticals, pesticides, or fragrances. Depending on the type of alcohol desired and the availability of the corresponding starting material, direct hydrogenation of the corresponding ester with hydrogen or reduction with reducing agents are often the methods of choice.

[0003] The synthesis of alcohols from esters is usually carried out using metal hydrides such as LiAlH 4 or NaBH 4 , by heterogeneous catalytic hydrogenation with hydrogen, or by homogeneous catalytic hydrogenation with hydrogen. Homogeneous catalytic hydrogenation with hydrogen often allows for less drastic reaction conditions while simultaneously achieving better selectivity. In particular, the use of ruthenium complexes with multidentate phosphorus-, sulfur-, and nitrogen-containing ligands has proven to be successful in this regard according to the state of the art; however, in recent years, alternatives containing manganese as the active metal have also been developed.

[0004] For example, Beller et al. describe in Angewandte Chemie International Edition 2016, Vol. 55, pages 15364-15368 the use of Mn complexes with a so-called pincer ligand of the PNP type for the hydrogenation of esters to alcohols. The ligands used have an NH unit at the center, to which two ethyl dialkyl phosphine units are attached. The manganese atom is in the +1 oxidation state and carries at least two carbonyl ligands. These catalysts can be used to hydrogenate a range of esters and lactones to the corresponding alcohols or diols.

[0005] Further Mn catalysts for the hydrogenation of esters to alcohols are known from WO2019 / 138216 and from the publication by Das Uttam Kumar et al in Green Chemistry 2020, 22(10), 3079-3082.

[0006] Disadvantages of these catalysts are the relatively high catalyst loadings of 2 mol% and the 10 mol% of KOtBu as a necessary cocatalyst, which must be used to achieve high conversions in the hydrogenation.

[0007] Milstein et al. describe in Chemistry, a European Journal 2017, Vol. 23, pages 5934-5938, the use of Mn complexes with a so-called pincer ligand of the PNN type for the hydrogenation of esters to alcohols. The described tridentate pincer ligand has a pyridyl group as the backbone and a phosphino and NHR group with an alkyl group as donor groups. These catalysts can be used to hydrogenate a range of esters and lactones to the corresponding alcohols or diols.

[0008] A disadvantage of the use of the aforementioned pincer ligands of the PNN type is their complex, multi-step synthesis using demanding reagents such as n-butyllithium starting from 2,6-dimethylpyridine. Further disadvantages of these catalysts are the relatively high catalyst loadings of at least 1 mol% and the use of expensive and difficult-to-handle KH as a necessary cocatalyst, which must be used to achieve high conversions in the hydrogenation. With the simpler and cheaper alkoxide bases, only low conversions can be achieved with this manganese catalyst.

[0009] Pidko et al. describe in Angewandte Chemie International Edition 2017, Vol. 56, pages 7531-7534 the use of Mn complexes with simple bidentate PN ligands for the hydrogenation of esters to alcohols. The ligands used here contain an NH 2 unit, an ethylene bridge, and a PR 2 (R = alkyl, aryl) group. The manganese atom is in the +1 oxidation state and carries at least two carbonyl ligands. An advantage here is that the ligands are easy to prepare.

[0010] However, these catalysts are only described for the hydrogenation of acyclic esters, not lactones. Further disadvantages of these catalysts are the relatively high catalyst loadings of 1 mol% and the very high loadings of 10-75 mol% of KOtBu as a cocatalyst, which must be used to achieve high conversions in the hydrogenation. Ester conversions above 90% can only be achieved with base loadings of at least 50 mol%, which is detrimental to an economical process.

[0011] In Organic Letters 2018, Vol. 20, pages 2654-2658, Clark et al. describe the use of Mn complexes with a so-called pincer ligand of the PNN type for the hydrogenation of esters to alcohols. The described tridentate pincer ligand has an NH group as the backbone and a pyridyl group and a ferrocene-bridged PPh2 group as donor groups. The manganese atom is in the +1 oxidation state and also carries three carbonyl ligands. An advantage here is that the ligands are easy to prepare. With this catalyst, a range of esters and lactones can be hydrogenated to the corresponding alcohols or diols.

[0012] The advantage of this catalyst is the low catalyst loading of only 0.1mol% which is necessary to hydrogenate, for example, the lactone sclareolide to moderate yields of 75% of the corresponding diol.

[0013] The disadvantage of using this PNN pincer ligand is its very complex, multi-step synthesis using demanding reagents such as n-butyllithium.

[0014] Another disadvantage of this catalyst is the relatively high loading of 10 mol% base as cocatalyst, as with the lactone sclareolide, required to achieve good conversions.

[0015] WO 2021 / 001240 A1 describes the use of easily prepared PNN ligands, which can be used to produce highly active ruthenium catalysts for the hydrogenation of esters. These catalysts require very little base as a cocatalyst or can be active without the addition of a base. However, their suitability as ligands for active manganese catalysts was previously unknown, and their structure differs from the ligands described above for manganese catalysts in ester hydrogenation, which is why it was not expected that highly active Mn catalysts could be produced with this ligand.

[0016] The object of the present invention was to find a process for the homogeneously catalyzed hydrogenation of esters to the corresponding alcohols, which does not have the disadvantages of the prior art or only has them to a minor extent, is simple to carry out with regard to the required apparatus and reaction conditions and enables the highest possible space-time yield.

[0017] In particular, the catalytically active complex should be directly producible from readily available starting materials, exhibit high activity in the hydrogenation of esters to alcohols, require as little cocatalyst as possible, and ultimately be easily disposed of. In this context, the complexing ligand is particularly important; it should be as simple to prepare as possible while still producing a highly active manganese catalyst.

[0018] Surprisingly, a process for the hydrogenation of an ester of the general formula (III) found, in which the radicals R a< and R b< each independently of one another represent a carbon-containing organic, linear or branched, non-cyclic or cyclic, saturated or unsaturated, aliphatic, aromatic or aryliphatic, unsubstituted or interrupted or substituted by heteroatoms or functional groups radical with a molecular mass of 15 to 10,000 g / mol, where both radicals R a< and R b< can also be bonded to one another, with molecular hydrogen to the alcohols at a temperature of 50 to 200°C and a pressure of 0.1 to 20 MPa abs in the presence of a manganese(I) complex (I), in which the manganese complex contains a tridentate ligand L with the general formula (II) and at least two carbonyl ligands, where R 1< , R 2< independently of one another represent an aliphatic hydrocarbon radical having 1 to 8 carbon atoms, an aromatic hydrocarbon radical having 6 or 10 carbon atoms or an araliphatic hydrocarbon radical having 7 to 12 carbon atoms, where the said hydrocarbon radicals are unsubstituted or substituted by 1 to 3 methoxy, thiomethoxy or dimethylamino groups, and the two radicals R 1< and R 2< can also be bonded to one another to form a 5 to 10-ring enclosing the phosphorus atom, R 3< , R 4< , R 5< , R 6< , R 10< , R 11< independently of one another represent hydrogen, linear C 1 to C 4 -alkyl, branched C 3 to C 4 -alkyl, methoxy, hydroxy, trifluoromethyl, nitrile or dialkylamino with independently from each other 1 to 4 carbon atoms per alkyl group, R 7< , R 8< , R 9< independently of each other represent hydrogen,linear C 1 to C 4 alkyl or branched C 3 to C 4 alkyl, n, m are independently 0 or 1, and the solid-dashed double lines represent a single or double bond, with the proviso that , in case of n = 1 both solid-dashed double lines represent a single bond and m is 1, and in case of n = 0 one solid-dashed double line represents a single bond and the other solid-dashed double line represents a double bond, where in the case of a double bond on the side facing the phenyl ring m = 1, in the case of a double bond on the side facing the pyridyl ring m = 0, or both solid-dashed double lines represent a single bond and m is 1.

[0019] The core of the process according to the invention is the use of a manganese(I) complex which contains a tridentate ligand L of the general formula (II) and at least two carbonyl ligands in the hydrogenation of esters with molecular hydrogen to the corresponding alcohols.

[0020] The tridentate ligand L is a so-called PNN ligand with the general formula (II) in which R 1< , R 2< independently of one another represent an aliphatic hydrocarbon radical having 1 to 8 carbon atoms, an aromatic hydrocarbon radical having 6 or 10 carbon atoms or an araliphatic hydrocarbon radical having 7 to 12 carbon atoms, where the said hydrocarbon radicals are unsubstituted or substituted by 1 to 3 methoxy, thiomethoxy or dimethylamino groups, and the two radicals R 1< and R 2< can also be joined together to form a 5 to 10-ring enclosing the phosphorus atom, R 3< , R 4< , R 5< , R 6< , R 10< , R 11< independently of one another represent hydrogen, linear C 1 to C 4 alkyl, branched C 3 to C 4 alkyl, methoxy, hydroxy, trifluoromethyl, nitrile or dialkylamino having independently of one another 1 to 4 Carbon atoms per alkyl group, R 7< , R 8< , R 9< independently of one another represent hydrogen, linear C 1 to C 4 alkyl or branched C 3 to C 4 alkyl, n,m are independently 0 or 1, and the solid-dashed double lines represent a single or double bond, with the proviso that , in case of n = 1 both solid-dashed double lines represent a single bond and m is 1, and in case of n = 0 one solid-dashed double line represents a single bond and the other solid-dashed double line represents a double bond, where in the case of a double bond on the side facing the phenyl ring m = 1, in the case of a double bond on the side facing the pyridyl ring m = 0, or both solid-dashed double lines represent a single bond and m = 1.

[0021] Tridentate means that ligand L (II) occupies three coordination sites in the manganese(I) complex (I). The three ligand donor atoms are the P and the two N atoms, hence the name PNN ligand.

[0022] With regard to the environment of the central donor atom, the ligand can basically have four different substructures, which are explained in more detail below. (1) In the case of n = 1, both solid-dashed double lines represent a single bond, and m is 1. This results in the general formula (IIa). Ligand (IIa) is neutral, thus having a charge of "0". In the case of n = 0, there are a total of three different substructures. (2) If n = 0 and the solid-dashed double line facing the phenyl ring represents a double bond and the solid-dashed double line facing the pyridyl ring represents a single bond, then m is 1. This results in the general formula (IIb). Ligand (IIb) is neutral, thus having a charge of "0." (3) If n = 0 and the solid-dashed double line facing the pyridyl ring represents a double bond and the solid-dashed double line facing the phenyl ring represents a single bond, then m is 0. This results in the general formula (IIc). Ligand (IIc) is neutral, thus having a charge of "0". (4) In the fourth variant, n = 0, but both solid-dashed double lines are single bonds and m is 1. The N atom thus has a negative charge. This results in the general formula (IId). The ligand (IId) thus has a charge of "-1."

[0023] The radicals R 1< and R 2< of the ligand (II) can vary widely and independently of one another represent an aliphatic hydrocarbon radical having 1 to 8 carbon atoms, an aromatic hydrocarbon radical having 6 or 10 carbon atoms or an araliphatic hydrocarbon radical having 7 to 12 carbon atoms, where the said hydrocarbon radicals can be unsubstituted or substituted by 1 to 3 methoxy, thiomethoxy or dimethylamino groups, and the two radicals R 1< and R 2< can also be linked to one another to form a 5 to 10-ring including the phosphorus atom.

[0024] In the case of an aliphatic hydrocarbon radical, it can be unbranched or branched, or linear or cyclic. The aliphatic hydrocarbon radicals preferably have 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms, and most preferably 1 to 2 carbon atoms. Specific examples include methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl (also referred to as tBu), and cyclohexyl (also referred to as Cy).

[0025] In the case of an aromatic hydrocarbon residue, it is phenyl (also called Ph), 1-naphthyl or 2-naphthyl.

[0026] Araliphatic hydrocarbon radicals contain aromatic and aliphatic elements, regardless of whether they are bonded to the phosphorus atom in the ligand L via an aliphatic or aromatic group. The araliphatic hydrocarbon radicals preferably have 7 to 10 carbon atoms, and particularly preferably 7 to 9 carbon atoms. Specific examples include o-tolyl, m-tolyl, p-tolyl, and benzyl.

[0027] In the case of a ring including the phosphorus atom, it is preferably a ring with 5 to 6 atoms, including the phosphorus atom. Examples include butane-1,4-diyl, pentane-1,5-diyl, and 2,4-dimethylpentane-1,5-diyl.

[0028] The above-mentioned aliphatic, aromatic, and araliphatic hydrocarbon radicals, which may also be bonded to form a ring enclosing the phosphorus atom, may be unsubstituted or substituted by 1 to 3 methoxy, thiomethoxy, or dimethylamino groups. The above-mentioned number of carbon atoms of the individual hydrocarbon radicals includes the carbon atoms of the methoxy, thiomethoxy, or dimethylamino groups. Specific examples include 3,5-dimethylphenyl, 3,5-dimethyl-4-methoxyphenyl, 3,5-dimethyl-4-thiomethoxyphenyl, and 3,5-dimethyl-4-(dimethylamino)phenyl.

[0029] The radicals R 1< and R 2< are particularly preferably phenyl, p-tolyl, o-tolyl, 4-methoxyphenyl, 2-methoxyphenyl, cyclohexyl, iso-butyl, tert-butyl, 3,5-dimethyl-4-methoxyphenyl, 3,5-tert-butyl-4-methoxyphenyl and 3,5-dimethyl-phenyl and very particularly preferably phenyl, p-tolyl, 3,5-dimethyl-4-methoxyphenyl, iso-butyl and cyclohexyl, where preferably both radicals are the same in each case.

[0030] The radicals R 3< , R 4< , R 5< , R 6< , R 10< and R 11< independently of one another represent hydrogen, linear C 1 to C 4 alkyl, branched C 3 to C 4 alkyl, methoxy, hydroxy, trifluoromethyl, nitrile or dialkylamino having, independently of one another, 1 to 4 carbon atoms per alkyl group. Examples of linear C 1 to C 4 alkyl include methyl, ethyl, n-propyl and n-butyl, and examples of branched C 3 to C 4 alkyl include isopropyl, sec-butyl and tert-butyl. Examples of dialkylamino include, in particular, amino radicals with identical alkyl groups, in particular dimethylamino, diethylamino, di-n-propylamino and di-n-butylamino.

[0031] Preferably, the radicals R 3< and R 4< independently of one another represent hydrogen or methyl and particularly preferably hydrogen.

[0032] The radical R 5< preferably represents hydrogen, methyl, isopropyl, sec-butyl, tert-butyl, methoxy, hydroxy or dialkylamino, particularly preferably hydrogen, methyl or hydroxy and very particularly preferably hydrogen.

[0033] Preferably, the radical R 6< represents hydrogen.

[0034] The radical R 10< preferably represents hydrogen, methyl, isopropyl, sec-butyl, tert-butyl or methoxy, particularly preferably hydrogen, methyl or tert-butyl and very particularly preferably hydrogen.

[0035] The radical R 11< preferably represents hydrogen, methyl, ethyl, methoxy, ethoxy or isopropyloxy and particularly preferably represents hydrogen, methyl or methoxy.

[0036] Particularly preferred ligands (II) are those in which R 3< , R 4< , R 5< , R 6< , R 10< and R 11< are hydrogen, R 3< , R 4< , R 5< , R 6< and R 10< are hydrogen and R 11< is methyl, R 3< , R 4< , R 5< , R 6< and R 10< are hydrogen and R 11< is methoxy, R 3< , R 4< , R 6< , R 10< and R 11< are hydrogen and R 5< is methyl, R 3< , R 4< , R 6< , R 10< and R 11< are hydrogen and R 5< is tert-butyl R 3< , R 4< , R 5< , R 6< and R 11< are hydrogen and R 10< is tert-butyl, and R 3< , R 4< , R 5< and R 6< are hydrogen and R 10< and R 11< are methyl.

[0037] The radicals R 7< , R 8< and R 9< independently of one another represent hydrogen, linear C 1 to C 4 alkyl or branched C 3 to C 4 alkyl. Examples of linear C 1 to C 4 alkyl include methyl, ethyl, n-propyl and n-butyl, and examples of branched C 3 to C 4 alkyl include isopropyl, sec-butyl and tert-butyl.

[0038] Preferably, the radicals R 7< , R 8< and R 9< independently of one another represent hydrogen, methyl, ethyl or n-propyl, particularly preferably hydrogen or methyl and most preferably hydrogen.

[0039] Particularly preferred ligands (II) are those in which R 7< , R 8< and R 9< stand for hydrogen, R 7< and R 9< stand for hydrogen and R 8< for methyl, R 7< stand for hydrogen and R 8< and R 9< stand for methyl, R 7< stand for methyl and R 8< and R 9< stand for hydrogen, and R 7< and R 8< stand for methyl and R 9< stand for hydrogen.

[0040] Particularly advantageous in the process according to the invention is the use of the ligands (II) in which (i) n and m are each 1 and the two solid-dashed double lines represent a single bond (structure (IIa)), or (ii) n is 0 and m is 1 and the solid-dashed double line facing the phenyl ring represents a double bond and the solid-dashed double line facing the pyridyl ring represents a single bond (structure (IIb)), and both radicals R 1< and R 2< stand for phenyl, p-tolyl, 3,5-dimethyl-4-methoxyphenyl, iso-butyl or cyclohexyl, the radicals R 3< , R 4< and R 6< stand for hydrogen, the radicals R 5< and R 10< stand for hydrogen, methyl or tert-butyl, the radical R 11< stands for hydrogen, methyl or methoxy, and the radicals R 7< , R 8< and R 9< stand for hydrogen or methyl.

[0041] Accordingly, the ligands L1, L2, L3, L4 and L5 are particularly suitable for the process according to the invention.

[0042] Ligand (II) can be obtained in a simple manner by condensation of a corresponding amine with a corresponding aldehyde or ketone (ligand (IIb) and (Ilc)) and a possible subsequent reduction (ligand (IIa)) and a possible subsequent deprotonation under basic conditions (ligand (IId)).

[0043] There are basically two different options for the condensation. Firstly, it is possible to use 2-picolylamine or a corresponding derivative as the amine component, and an appropriately substituted phosphanylbenzaldehyde or a corresponding ketone as the aldehyde or ketone component. Ligand (IIb)

[0044] On the other hand, it is also possible to use an appropriately substituted phosphanylphenylmethanamine as the amine component and picolinaldehyde or a corresponding derivative thereof as the aldehyde or ketone component. Ligand (IIc)

[0045] The corresponding starting materials (amines, ketones, or aldehydes) are usually commercially available or can be synthesized using well-known methods. The synthesis of the ligands (IIb) and (IIc) is usually carried out under a protective gas atmosphere. both componentsare usually reacted with one another in a solvent at a temperature of 50 to 200°C. Suitable solvents include, for example, aliphatic alcohols such as methanol, ethanol or isopropanol and aromatic hydrocarbons such as toluene or xylenes. The two starting compounds can be used in stoichiometric amounts. However, it is also possible to use one of the two components in excess, for example to increase the conversion of the other component. This is particularly useful if the other component is difficult to access. If an excess is used, the molar ratio of the two starting compounds is generally in the range of > 1 to ≤ 2. The reaction time is usually between a few minutes and several hours. Typical reaction times are 10 minutes to 5 hours and preferably 30 minutes to 3 hours.The reaction mixture can be worked up and the ligand isolated using conventional methods. However, it is preferable to remove the added solvent and water under vacuum.

[0046] The ligands (IIb) and (IIc) can now be used to prepare the manganese(I) complex (I).

[0047] By reducing the ligand (IIb) or (IIc) with reducing agents such as sodium borohydride or lithium aluminum hydride, or catalytically with hydrogen, the ligand (IIa) can be obtained from the ligands (IIb) and (IIc) in a simple manner. The reaction can be carried out using the usual knowledge of the person skilled in the art.

[0048] In a particularly advantageous synthesis, the condensation described above and the reduction to ligand (IIa) are carried out directly one after the other in a one-pot reaction, without prior isolation of ligands (IIb) and (IIc). For this purpose, after the condensation has completed, the reducing agent is added directly to the reaction mixture and allowed to react for a further period of time. A few minutes to several hours are usually sufficient for this. Typical reaction times are 10 minutes to 5 hours, and preferably 30 minutes to 3 hours. The reaction mixture can then be worked up and the ligand isolated using conventional methods. Specific reference is made to the information given for the workup and isolation of ligands (IIb) and (IIc).

[0049] Ligand (IIa) can also be formed from the ligands (IIb) and (IIc) bound in the manganese(I) complex (I) under reaction conditions by hydrogenation with the supplied hydrogen.

[0050] The anionic ligand (IId) is formed from the ligand (IIa) by reaction with a strong base as a result of the loss of the hydrogen atom on the nitrogen as a proton.

[0051] Suitable strong bases include NaOMe, NaOEt, KOEt, KOt-Bu, or KOMe. Typically, this reaction is not carried out specifically with the free ligand (IIa). Rather, the ligand (IId) can form in the manganese(I) complex (I) under hydrogenation conditions in the presence of a strong base.

[0052] The manganese(I) complex (I) to be used in the process according to the invention carries, in addition to the ligand II, at least two carbonyl ligands (=CO).

[0053] In the process according to the invention, the oxidation state of manganese is +1.

[0054] The manganese(I) complex (I) preferably used in the process according to the invention has the general formula (I) [Mn(L)(CO) 2+n X 1-n ]Z (n) (I) where X stands for an anionic monodentate ligand with the charge "-1" Z stands for an anionic counterion with the charge "-1" n stands for 0 or 1.

[0055] The index n indicates whether the manganese(I) complex (I) carries two (n = 0) or three CO ligands (n = 1). If n = 0, the anionic ligand is located on the manganese. If n = 1, the manganese complex is cationic, and the charge is balanced by the anionic counterion Z.

[0056] As manganese(I) complex (I) in the process according to the invention, a ruthenium complex is preferred in which X represents an anionic ligand selected from the group H -< , F -< , Cl -< , Br -< , I -< , OH -< , C 1 to C 6 -alkoxy, C 1 to C 6 -carboxy, methylallyl, acetylacetonato, RSO 3 -< , CF 3 SO 3 ', CN -< and BH 4 -< , preferably Br -< or Cl -< Z represents an anionic counterion selected from the group F -< , Cl -< , Br -< , I -< , OH -< , C 1 to C 6 -alkoxy, C 1 to C 6 -carboxy, methylallyl, acetylacetonato, RSO 3 , CF 3 SO 3 -< , CN -< , BH 4 -< , BF 4 -< , PF 6 -< ClO 4 -< , NO 3 -< , BPh 4 -< , preferably Br -< , CI -< , C 1 to C 6 -alkoxy and C 1 to C 6 -carboxy.

[0057] Preferred examples of manganese(I) complexes (I) include [Mn(L)(CO) 2 Br], [Mn(L)(CO) 2 CI], [Mn(L)(CO) 2 I], [Mn(L)(CO) 2 OMe], [Mn(L)(CO) 2 CN], [Mn(L)(CO) 2 OH], [Mn(L)(CO) 2 H], [Mn(L)(CO) 3 ][Br], [Mn(L)(CO) 3 ][Cl], [Mn(L)(CO) 3 ][I], [Mn(L)(CO) 3 ][OtBu], [Mn(L)(CO) 3 ][CN], [Mn(L)(CO) 3 ][NO 3 ], [Mn(L)(CO) 3 ][CIO 4 ], [Mn(L)(CO) 3 ][BF 4 ], [Mn(L)(CO) 3 ][PF 6 ] where L represents the neutral ligands (IIa), (IIb) or (IIc).

[0058] The process according to the invention is very particularly preferably carried out in the presence of manganese(I) complexes (I) in which the ligand (II) stands for the ligand (IIa), (IIb) or (IIc) and the radicals R 1< , R 2< each stand for phenyl, p-tolyl, 3,5-dimethyl-4-methoxyphenyl, iso-butyl or cyclohexyl, the radicals R 5< and R 10< independently of one another stand for hydrogen, methyl or tert-butyl, the radical R 11< independently of one another stands for hydrogen, methyl or methoxy, the radicals R 7< , R 8< and R 9< independently of one another stand for hydrogen or methyl.

[0059] Accordingly, the manganese(I) complexes (I) K1, K2, K3, K4 and K5 are particularly suitable for the process according to the invention.

[0060] The manganese(I) complexes (I) to be used in the process according to the invention can be obtained in various ways. A preferred possibility is to use, as the manganese-containing starting material, a compound in which the manganese is already present in the form of a complex, hereinafter referred to as the Mn precursor complex (IV), and to react this with the ligand L. Accordingly, a process is preferred in which the manganese(I) complex (I) is obtained by reacting ligand (II) with a Mn precursor complex (IV).

[0061] In principle, a wide variety of Mn complexes can be used as the Mn precursor complex (IV). In many cases, it is not necessary for the Mn precursor complex (IV) to already contain the ligands X or carbonyl and, if appropriate, the noncoordinating anion Z of the desired manganese complex (I). The ligand X, CO, and the noncoordinating anion Z can, in many cases, also be added separately to the synthesis batch. To keep the synthesis effort low, it is advantageous to use easily accessible or readily available complexes as the Mn precursor complex (IV). Such complexes are well known to the person skilled in the art. Likewise, the person skilled in the art is also familiar with the exchange of ligands in manganese-containing complexes.

[0062] In principle, all anionic ligands already described under ligand X can be considered as anionic ligands in the Mn precursor complex (IV).

[0063] The reaction of the Mn precursor complex (IV) with the ligand L is typically carried out at a Mn / L molar ratio of 0.8 to 20, preferably 0.9 to 10, and particularly preferably 0.9 to 1.1. To achieve the highest possible degree of conversion, it is advantageous to use a Mn precursor complex (IV) with only mono- and bidentate ligands in order to utilize the complexing effect of the tridentate ligand L. The reaction is typically carried out anhydrous, but in the presence of a solvent and under a protective gas atmosphere. Suitable solvents include, for example, aliphatic alcohols such as methanol, ethanol, or isopropanol, and aromatic hydrocarbons such as toluene or xylenes. In general, manganese in the Mn precursor complex (IV) has the same oxidation state as in the subsequent manganese(I) complex (I), i.e., the +I oxidation state.

[0064] Suitable Mn precursor complexes (IV) include, for example, [Mn(CO) 5 Br], [Mn(CO) 5 Cl], [Mn(CO) 5 I], [Mn(CO) 5 F], [Mn 2 (CO) 10 ], MnCl 2 , Mn(OAc) 2 , Mn(OAc) 3 , Mn(AcAc) 2 , Mn(AcAc) 3 , MnBr 2 , MnI 2 , MnCO 3 , Mn(NO 3 ) 2 and Mn(CIO 4 ) 2 . (AcAc=acetylacetonate)

[0065] The manganese complex (I) can be isolated from the resulting reaction mixture, for example by precipitation or crystallization.

[0066] However, to carry out the hydrogenation according to the invention, it is generally not necessary to first isolate the manganese(I) complex (I) after its preparation. Rather, in the interests of simplified process control, it is advantageous to prepare the manganese(I) complex (I) as described above from a Mn precursor complex (IV) and the ligand L in the presence of a solvent and to carry out the hydrogenation according to the invention directly in the resulting reaction mixture.

[0067] In the process according to the invention, different manganese(I) complexes (I), in particular mixtures of cationic and neutral manganese(I) complexes (I) containing the same ligand L (II) can also be used.

[0068] The esters to be used in the process according to the invention can be of a wide variety of types. Thus, in principle, linear or branched, non-cyclic or cyclic, saturated or unsaturated, aliphatic, aromatic or araliphatic, unsubstituted or interrupted by heteroatoms or functional groups, and of various molecular weights, from low to high molecular weight, can be used.

[0069] The preferred ester is an ester of the general formula (III) in which the radicals R a< and R b< each independently of one another represent a carbon-containing organic, linear or branched, non-cyclic or cyclic, saturated or unsaturated, aliphatic, aromatic or araliphatic, unsubstituted or interrupted or substituted by heteroatoms or functional groups, having a molar mass of 15 to 10,000 g / mol, where both radicals R a< and R b< can also be linked to one another.

[0070] In the case of branched radicals R a< and R b<, these can be singly or multiply branched. Likewise, in the case of cyclic radicals, these can be singly or multiply cyclic. Likewise, in the case of unsaturated radicals, these can be singly or multiply unsaturated, with both double bonds and triple bonds being possible. Heteroatoms are atoms which are neither carbon nor hydrogen. Preferred examples of heteroatoms are oxygen, nitrogen, sulfur, phosphorus, fluorine, chlorine, bromine and iodine, and particularly preferred examples are oxygen, nitrogen, fluorine, chlorine and bromine. Functional groups are a further description of groups which contain at least one heteroatom.For example, a hydrocarbon chain interrupted by -O- can be considered both as a hydrocarbon chain interrupted by an oxygen heteroatom and as a hydrocarbon chain interrupted by an ether group. Other non-limiting examples include amino groups (-NH 2 , -NH-, -N<), aldehyde groups (-CHO), carboxyl groups (-COOH), amide groups (-CONH 2 , -CONH-, -CON<), nitrile groups (-CN), isonitrile groups (-NC), nitro groups (-NO 2 ), sulfonic acid groups (-SO 3 ), keto groups (>CO), imino groups (>CNH, >CN-), ester groups (-CO-O-), anhydride groups (-CO-O-CO-), and imido groups (-CO-NH-CO-, -CO-NR-CO-). Of course, they can also contain several so-called functional groups. Examples of this include fats.

[0071] If the residues R a< and R b< are connected to each other, cyclic esters are formed, which are also called lactones.

[0072] The molar masses of the radicals R a< and R b< are generally 15 to 10,000 g / mol, preferably 15 to 5,000 g / mol and particularly preferably 15 to 2,000 g / mol.

[0073] In the process according to the invention, preference is given to using esters having a molecular weight of 74 to 20,000 g / mol, particularly preferably of 74 to 10,000 g / mol, very particularly preferably of 74 to 5,000 g / mol, especially of 74 to 2,000 g / mol and in particular of 74 to 1,000 g / mol.

[0074] The molecular hydrogen (H 2 ) to be used in the process according to the invention can be supplied either undiluted or diluted with an inert gas, for example nitrogen. It is advantageous to supply a hydrogen-containing gas with the highest possible hydrogen content. A hydrogen content of ≥ 80 vol.% is preferred, more preferably ≥ 90 vol.%, most preferably ≥ 95 vol.%, and in particular ≥ 99 vol.%.

[0075] In a very general embodiment of the process according to the invention, the manganese(I) complex (I), the ester to be hydrogenated and hydrogen are fed to a suitable reaction apparatus and the mixture is reacted under the desired reaction conditions.

[0076] In principle, reaction apparatuses suitable for gas / liquid reactions at the given temperature and pressure can be used as reaction apparatuses in the process according to the invention. Suitable standard reactors for gas / liquid and liquid / liquid reaction systems are described, for example, in KD Henkel, "Reactor Types and Their Industrial Applications," in Ullmann's Encyclopedia of Industrial Chemistry, 2005, Wiley-VCH Verlag GmbH & Co. KGaA, DOI: 10.1002 / 14356007.b04_087, Chapter 3.3 "Reactors for Gas-Liquid Reactions." Examples include stirred tank reactors, tubular reactors, and bubble column reactors. Pressure-resistant stirred tanks are also generally referred to as autoclaves.

[0077] The manganese(I) complex (I) can be fed directly to the reaction apparatus in the form of the previously synthesized manganese(I) complex (I).

[0078] It is significantly simpler if the manganese(I) complex (I) is formed in situ from a Mn precursor complex (IV) and ligand L (II). In situ stands for "on site" and means that the manganese(I) complex (I) is formed by adding Mn precursor complex (IV) and ligand L (II) to the reaction apparatus. Advantageously, a molar ratio of ligand L (II) to manganese of 0.5 to 5, preferably ≥ 0.8 and particularly preferably ≥ 1, and preferably ≤ 3, particularly preferably ≤ 2, and most preferably ≤ 1.5, is used for this purpose. This in situ variant eliminates the need to isolate the manganese(I) complex (I) beforehand.

[0079] The process according to the invention can be carried out in the presence or absence of a solvent. If a solvent is used, it serves, for example, to dissolve the manganese(I) complex (I) or a manganese precursor complex (IV) and the ligand L, but also, if appropriate, to dissolve the ester to be hydrogenated. This solvent can also act as a solvent, especially for low-molecular-weight esters.

[0080] If solvents are used, preference is given to solvents with more or less pronounced polar properties that are not themselves hydrogenated under the reaction conditions. Preferred examples include aliphatic alcohols such as methanol, ethanol or isopropanol, as well as aromatic hydrocarbons such as toluene or xylenes and ethers such as tetrahydrofuran or 1,4-dioxane. The amount of solvent used can vary widely. However, amounts in the range of 0.1 to 20 g of solvent per g of ester to be hydrogenated are usual, preferably 0.5 to 10 g of solvent per g of ester to be hydrogenated and particularly preferably 1 to 5 g of solvent per g of ester to be hydrogenated.

[0081] The ester to be hydrogenated can be added directly as pure, undiluted ester, or diluted or dissolved in a solvent. Criteria for the form in which the ester to be hydrogenated is added are often purely practical, such as the nature of the ester present and its handling. For example, it is desirable that the ester be present in the reaction mixture in liquid form under the reaction conditions.

[0082] The molar ratio between the ester to be hydrogenated and the manganese complex (I) can vary within a wide range in the process according to the invention. In general, the molar ratio mentioned in the reaction mixture to be hydrogenated is 1 to 100,000, preferably 10 to 25,000, particularly preferably 100 to 5,000, and most preferably 500 to 20,000.

[0083] The process according to the invention is carried out at a temperature of 50 to 200°C, preferably at ≤ 170°C and particularly preferably at ≤ 150°C. The pressure is 0.1 to 20 MPa abs, preferably ≥ 1 MPa abs and particularly preferably ≥ 5 MPa abs, and preferably ≤ 15 MPa abs and particularly preferably ≤ 10 MPa abs.

[0084] The reaction time or average residence time in which the reaction mixture is present under the reaction conditions can also vary widely, but is usually in the range from 0.1 to 100 hours, preferably ≥ 1 hour and particularly preferably ≥ 2 hours, and preferably ≤ 80 hours and particularly preferably ≤ 60 hours.

[0085] Furthermore, it has been shown that the hydrogenation according to the invention is generally positively influenced by the presence of a base, ultimately enabling significantly higher conversions. Therefore, in most cases it is advantageous to carry out the hydrogenation in the presence of a base. In principle, the bases can also be present in the reaction mixture as a solid, but preference is given to bases that are dissolved in the reaction mixture. Examples of possible bases include alkoxides, hydroxides, alkali metal and alkaline earth metal carbonates, amides, basic aluminum and silicon compounds, and hydrides. Particular preference is given to using alkoxides or amides as the base, preferably sodium methoxide, potassium methoxide, sodium hydroxide, sodium ethoxide, potassium ethoxide, potassium tert-butylate, sodium tert-butylate, sodium borohydride, or sodium hydride.

[0086] If the process according to the invention is carried out in the presence of a base, this is generally used in excess relative to the manganese(I) complex (I). A molar ratio of the base to the ruthenium complex (I) of 1 to 1000, preferably 2 to 20, particularly preferably 1 to 10, is preferably used.

[0087] The process according to the invention can be carried out continuously, semibatchwise, discontinuously, with product as solvent, or in a straight pass without backmixing. The manganese(I) complex, the ester to be hydrogenated, the hydrogen, any solvent, and any base can be fed in simultaneously or separately.

[0088] In the batchwise procedure, the manganese complex (I) or a manganese precursor complex (IV) as well as the ligand L (II), the ester to be hydrogenated and, if appropriate, solvent and a base are usually placed in the reaction apparatus. The desired reaction pressure is adjusted under the desired reaction conditions by adding hydrogen while mixing. The reaction mixture is then left under the desired reaction conditions for the desired time. Hydrogen is added if necessary. After the desired reaction time, the reaction mixture is cooled or depressurized. The corresponding alcohols can be obtained as reaction products through subsequent workup. The batchwise reaction is preferably carried out in a stirred tank.

[0089] In the continuous procedure, the manganese(I) complex (I) or a Mn precursor complex (IV) as well as the ligand L (II), the ester to be hydrogenated and, if necessary, solvent and a base are continuously fed to the reaction apparatus and an appropriate amount is continuously removed for workup and isolation of the corresponding alcohol formed.

[0090] The continuous reaction is preferably carried out in a stirred tank or a stirred tank cascade.

[0091] The hydrogenation product can be separated from the hydrogenation mixture by processes known to those skilled in the art, such as distillation and / or flash evaporation, and the remaining catalyst can be used in further reactions. In the preferred embodiment, the addition of solvents is advantageously omitted, and the aforementioned reactions are carried out in the substrate to be reacted or in the product and, if appropriate, in high-boiling by-products as the solvent. Continuous reaction with reuse or recycling of the homogeneous catalyst is particularly preferred.

[0092] In the ester hydrogenation according to the invention, a terminal -CH 2 OH and a terminal -OH group are formed from the -CO-O- ester group. In the case of the ester (III), the two corresponding alcohols R a < -CH 2 OH and R b < -OH are formed according to the following reaction equation. Esters (III)

[0093] When using cyclic esters, so-called lactones, the two residues R a< and R b< are linked together and the corresponding diol is formed.

[0094] The process according to the invention enables the production of alcohols by homogeneously catalyzed hydrogenation of esters in high yield and selectivity. The hydrogenation can be carried out industrially using standard laboratory equipment for hydrogenation reactions and allows the use of a wide variety of esters as substrates.

[0095] A further embodiment of the invention is the conversion of sclareolide to ambroxidol (ambrox-1,4-diol), which is a precursor to the important fragrance (-) ambrox. Ambroxidol can be converted to (-) ambrox by cyclization, as described, for example, in WO 2017 / 140909.

[0096] The particular advantages of the process according to the invention are based on the special, tridentate PNN ligands. Due to its tridentate nature, the ligand coordinates tightly to manganese, yet is easy to prepare and, after formation of corresponding manganese(I) complexes, yields catalysts with high hydrogenation activities. Furthermore, the ligand according to the invention is relatively insensitive to oxidation, thus also being advantageous in handling and exhibiting high storage stability.

[0097] Among the particular advantages of the ligand according to the invention are its easy accessibility and the possibility of easily varying the basic structure by replacing hydrogen atoms with various organic residues. The ligand can generally be prepared from readily available starting materials through a simple one-pot synthesis. Easily accessible manganese precursor complexes that are commercially available in large quantities can be used as manganese-containing starting materials. Examples General information

[0098] Unless otherwise stated, all reactions were prepared under an argon atmosphere using so-called "Schlenk" and high vacuum techniques or in an MBraun inert atmosphere glove box at room temperature. Organic solvents were purchased from Aldrich or Acros. Commercially available starting compounds were purchased from Aldrich, ABCR, or TCI and used as received. NMR spectra were measured on Bruker AVANCE III 300, Bruker AVANCE III 400, and Bruker AVANCE III 500 spectrometers, and the proton ( 1 < H) or carbon ( 13 < C) resonance signals of the solvent served as reference. Chemical shifts (δ) are given in ppm. 31 < P NMR spectra refer to an external standard (ampoule D 3 PO 4 ) from the Organic Chemistry Institute of the University of Heidelberg. GC analyses were performed on an Agilent Technologies 6890N gas chromatograph equipped with an FID detector; column used: DB-FFAP (30 m×0.32 mm×0.25 µm).Initial temperature - 55 °C, hold time - 1 min; ramp 25 °C / min to 250 °C, hold time - 8 min.

[0099] Example 1 describes the preparation of a representative ligand II. The other ligands were prepared analogously to this procedure. Example 1: Preparation of ligand L1

[0100]

[0101] At room temperature, (2-(Diphenylphosphaneyl)phenyl)methanamine (1.00 g, 3.43 mmol) was added to a solution of picolinaldehyde (368 mg, 3.43 mmol) in ethanol (10 ml), and the resulting mixture was stirred at room temperature for 2 h. NaBH 4 (208 mg, 5.49 mmol) was added, and stirring was continued at room temperature for a further 2 h. Subsequently, saturated aqueous NaHCO 3 solution (15 ml) and CH 2 Cl 2 (25 ml) were added. After phase separation, the aqueous phase was extracted with CH 2 Cl 2 (2 x 25 ml). The combined organic phase was dried (Na 2 SO 4 ) and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (hexane / EtOAc / NEt 3 , 9:1 to 1:1; a mixture of 10% NEt 3 in EtOAc was used) and N-(2-(diphenylphosphaneyl)benzyl)-1-(pyridin-2-yl)methanamine (L1) was obtained as a colorless oil (600 mg, 46% yield).

[0102] 1< H NMR(500 MHz, CD 2 CI 2 ) δ 8.48-8.46 (m, 1H), 7.57 (td, J= 7.7, 1.8 Hz, 1H), 7.54-7.51 (m, 1H), 7.36-7.30 (m, 7H), 7.28-7.24 (m, 4H), 7.19-7.10 (m, 4H), 6.91 (ddd, J= 7.7, 4.5, 1.4 Hz, 1H), 4.02 (d, J = 1.7 Hz, 2H), 3.79 (s, 2H).

[0103] 31< P NMR (203 MHz, CD 2 CI 2 ) δ -15.94.

[0104] HRMS (ESI) C 25 H 23 N 2 P ([M] +< ): Calculated: 382.1599; Found: 382.1611.

[0105] Example 2 describes the preparation of a representative manganese(I) catalyst complex (I) with a ligand II. Example 2: Preparation of catalyst K1

[0106]

[0107] A solution of [Mn(CO) 5 Br] (720 mg, 2.62 mmol) in 15 mL of toluene was added under an argon atmosphere to a solution of ligand L1 (1 g, 2.62 mmol) in 15 mL of toluene. The reaction mixture was stirred at 60-80°C for 30 minutes until no visible CO evolution was observed. The mixture was then stirred for a further 16 hours at 110°C, during which a yellow precipitate formed. After cooling to room temperature, the toluene was removed from the reaction mixture under vacuum. The yellow residue was washed with 10 mL of absolute hexane and then with 10 mL of absolute diethyl ether under an argon atmosphere and filtered off. The filter cake was dried under high vacuum, yielding catalyst K1 as a yellow powder with a yield of 80% (1.2 g). The catalyst complex is stored at 0°C in the absence of light.

[0108] 1< H NMR (500 MHz, CD 2 CI 2 ) δ 9.09 (d, J = 5.5 Hz, 1H), 8.07 (s, 2H), 7.67 (t, J =7.1 Hz, 1H), 7.57 - 7.22 (m, 11H), 7.05 (t, J = 8.5 Hz, 2H), 6.81 (t, J = 8.2 Hz, 1H), 4.59 - 3.59 (m, 5H).

[0109] 13< C NMR (126 MHz, CD 2 CI 2 ) δ 154.62, 151.77, 135.76 (d, J = 16.5 Hz), 133.55 - 133.09 (m), 129.76, 129.56, 129.00, 128.79 (d, J = 3.2 Hz), 128.70, 127.93 (d, J = 8.4 Hz), 127.18 (dd, J = 7.9, 2.2 Hz), 126.13 (d, J = 5.2 Hz), 125.92 (d, J = 2.0 Hz), 124.93 (d, J = 9.0 Hz), 124.63 (d, J = 9.5 Hz), 120.93, 117.01, 56.86 (d, J = 2.6 Hz), 55.71 (d, J = 8.1 Hz).

[0110] 31< P NMR (203 MHz, CD 2 CI 2 ) δ 68.39. Example 3: Production of catalyst K2

[0111]

[0112] A solution of [Mn(CO) 5 Br] (85 mg, 0.31 mmol) in 10 mL of toluene was added under an argon atmosphere to a solution of ligand L2 (0.155 g, 0.31 mmol) in 10 mL of toluene. The reaction mixture was stirred at 60-80°C for 30 minutes until no visible CO evolution was observed. The mixture was then stirred for a further 16 hours at 110°C, during which a yellow precipitate formed. After cooling to room temperature, the toluene was removed from the reaction mixture under vacuum. The yellow residue was washed with 10 mL of absolute hexane and then with 10 mL of absolute diethyl ether under an argon atmosphere and filtered off. The filter cake was dried under high vacuum, yielding catalyst K2 as a yellow powder with a yield of 75% (0.16 g). The catalyst complex is stored at 0°C in the absence of light. Example 4: Preparation of catalyst K3

[0113]

[0114] A solution of [Mn(CO) 5 Br] (97 mg, 0.35 mmol) in 10 mL of toluene was added under an argon atmosphere to a solution of ligand L3 (0.14 g, 0.35 mmol) in 10 mL of toluene. The reaction mixture was stirred at 60-80°C for 30 minutes until no visible CO evolution was observed. The mixture was then stirred for a further 16 hours at 110°C, during which a yellow precipitate formed. After cooling to room temperature, the toluene was removed from the reaction mixture under vacuum. The yellow residue was washed with 10 mL of absolute hexane and then with 10 mL of absolute diethyl ether under an argon atmosphere and filtered off. The filter cake was dried under high vacuum, yielding catalyst K2 as a yellow powder with a yield of 56% (0.115 g). The catalyst complex is stored at 0°C in the absence of light. Example 5: Preparation of catalyst K4

[0115]

[0116] A solution of [Mn(CO) 5 Br] (0.36 g, 1.31 mmol) in 10 mL of toluene was added under an argon atmosphere to a solution of ligand L4 (0.54 g, 1.31 mmol) in 10 mL of toluene. The reaction mixture was stirred at 60-80°C for 30 minutes until no visible CO evolution was observed. The mixture was then stirred for a further 16 hours at 110°C, during which a yellow precipitate formed. After cooling to room temperature, the toluene was removed from the reaction mixture under vacuum. The yellow residue was washed with 10 mL of absolute hexane and then with 10 mL of absolute diethyl ether under an argon atmosphere and filtered off. The filter cake was dried under high vacuum, yielding catalyst K2 as a yellow powder with a yield of 82% (0.65 g). The catalyst complex is stored at 0°C in the absence of light. Example 5: Preparation of catalyst K5

[0117]

[0118] A solution of [Mn(CO) 5 Br] (0.236 g, 0.86 mmol) in 10 mL of toluene was added under an argon atmosphere to a solution of ligand L5 (0.34 g, 0.86 mmol) in 10 mL of toluene. The reaction mixture was stirred at 60-80°C for 30 minutes until no visible CO evolution was observed. The mixture was then stirred for a further 16 hours at 110°C, during which a yellow precipitate formed. After cooling to room temperature, the toluene was removed from the reaction mixture under vacuum. The yellow residue was washed with 10 mL of absolute hexane and then with 10 mL of absolute diethyl ether under an argon atmosphere and filtered off. The filter cake was dried under high vacuum, yielding catalyst K2 as a yellow powder with a yield of 75% (0.38 g). The catalyst complex is stored at 0°C in the absence of light. Examples 6, 7, 8 and 9: Hydrogenation of sclareolide

[0119] In an argon-filled glove box, sclareolide (375 mg, 1.5 mmol), manganese catalyst (0.1 mol%), KOtBu (3.36 mg, 2 mol%), and dry ethanol (2 mL) were placed in 10 mL vials with crimp caps and PTFE-coated magnetic stir bars. The vials were sealed with the crimp cap containing a rubber septum, the septum was pierced with a cannula, and the vials were placed in a HEL CAT-7 autoclave. The autoclave was sealed, removed from the glove box, and pressurized with 50 bar of H2 under inert conditions. The autoclave was then inserted into a preheated aluminum block. The reaction mixture was stirred at 100°C for 20 h, cooled in an ice bath, and the remaining H2 pressure was carefully vented. Then, mesitylene is added to the respective batches as an internal standard and the reaction mixtures are analyzed by gas chromatography. Example catalyst Sales volume GC yield diol 6 K1 full 93% 7 K2 full 91.5% 8 K4 34% 34% 9 K5 full 94% Example 10: Hydrogenation of sclareolide

[0120]

[0121] In an argon-filled glove box under inert conditions, sclareolide (750 mg, 3 mmol), K1 (1.7 mg, 0.003 mmol), potassium tert-butylate (3.36 mg, 0.003 mmol), and 4 ml of dry ethanol are weighed into a 100 ml Premex autoclave equipped with a Teflon insert and magnetic stir bar. The autoclave is sealed and vented. It is then flushed three times with nitrogen and then three times with hydrogen and pressurized with hydrogen to a cold pressure of 40 bar. The reaction mixture is then heated and stirred in the autoclave for 20 h at 90°C. After cooling to room temperature, the remaining hydrogen is vented, and the reaction mixture is analyzed by GC. Sclareolide conversion: 98%, diol yield: 92%. (2R,8aS)-1-(2-hydroxyethyl)-2,5,5,8a-tetramethyldecahydronaphthalen-2-ol 1< H NMR (400 MHz, CDCl;) δ 3.78 (dt, J = 10.2, 4.4 Hz, 1H), 3.46 (ddd, J =10.2, 8.2, 5.7 Hz, 1H), 3.08 (s, 2H), 1.90 (dt, J = 12.3, 3.3 Hz, 1H), 1.72 - 1.21 (m, 10H), 1.19 (s, 3H), 1.13 (dd, J = 13.4, 4.4 Hz, 1H), 0.99 - 0.91 (m, 2H), 0.88 (s, 3H), 0.79 (s, 6H). 13< C NMR (101 MHz, CDCl:) δ 73.03, 64.09, 59.18, 56.04, 44.29, 41.91, 39.36, 38.98, 33.41, 33.28, 27.89, 24.64, 21.48, 20.47, 18.42, 15.31. Beispiel 11: Hydrierung von Sclareolid

[0122]

[0123] In an argon-filled glove box, sclareolide (375 mg, 1.5 mmol), manganese catalyst K1 (0.1 mol%), KOtBu (3.36 mg, 2 mol%), and dry ethanol (2 ml) are placed into a 10 ml vial with a crimp cap and PTFE-coated magnetic stir bar. The vials are sealed with the crimp cap containing a rubber septum, the septum is pierced with a cannula, and the vials are placed in a HEL CAT-7 autoclave. The autoclave is sealed, removed from the glove box, and under inert conditions, 50 bar of H2 is applied. The autoclave is then inserted into a preheated aluminum block. The reaction mixture is stirred at 90°C for 16 h, cooled in an ice bath, and the remaining H2 pressure is carefully vented. The reaction mixture is filtered through silica, and the silica is washed several times with ethanol. The ethanol is evaporated to dryness from the combined filtrates in vacuo, and the product is analyzed by NMR.The isolated yield of sclareoldidiol is quantitative (yield >99%) and according to the 1H NMR spectrum it is a pure substance. Example 12: Hydrogenation of sclareolide

[0124]

[0125] In an argon-filled glove box under inert conditions, sclareolide (375 mg, 1.5 mmol), K1 (0.88 mg, 0.1 mol%), potassium ethylate (2.52 mg, 2 mol%), and 2 ml of dry ethanol are weighed into a 30 ml Premex autoclave equipped with a Teflon insert and magnetic stir bar. The autoclave is sealed and vented. It is then flushed three times with nitrogen and then three times with hydrogen, and pressurized with hydrogen to a cold pressure of 40 bar. The reaction mixture is then heated and stirred in the autoclave for 16 h at 90°C. After cooling to room temperature, the remaining hydrogen is vented, and the reaction mixture is analyzed by GC. Sclareolide conversion: >99%, diol yield: 98%. Examples 11, 12, 13, 14 and 15: Hydrogenation of other esters with catalyst K1

[0126] In an argon-filled glove box, the respective ester (3 mmol), manganese catalyst K1 (1.72 mg, 0.1 mol%), KOtBu (6.72 mg, 2 mol%), and dry ethanol (4 mL) are placed in 10 mL vials with crimp caps and PTFE-coated magnetic stir bars. The vials are sealed with the crimp cap containing a rubber septum, the septum is pierced with a cannula, and the vials are placed in a HEL CAT-7 autoclave. The autoclave is closed, removed from the glove box, and under inert conditions, 50 bar of H2 is injected. The autoclave is then inserted into a preheated aluminum block. The reaction mixture is stirred at 100°C for 20 h, cooled in an ice bath, and the remaining H2 pressure is carefully vented. The reaction mixtures are filtered through silica, and the silica is washed several times with ethanol. The ethanol is evaporated from the combined filtrates to dryness under vacuum, and the product is analyzed by NMR. Example 11 Yield 99% Example 12 Yield 99% Example 13 Yield 99% Example 14 Yield 96% Example 15 Yield 99% Phenylmethanol, 2a

[0127] 1< H NMR (301 MHz, CDCl 3 ) δ 7.39 - 7.26 (m, 5H), 4.66 (s, 2H), 1.98 (s, 1H). 13< C NMR (76 MHz, CDCl 3 ) δ 140.89, 128.58, 127.66, 127.02, 65.34. Dodecan-1-ol, 2b

[0128] 1< H NMR (301 MHz, CDCl 3 ) δ 3.64 (t, J = 6.6 Hz, 2H), 1.55 (q, J = 7.1 Hz, 2H), 1.37-1.26 (m, 18H), 0.93 - 0.83 (m, 3H).

[0129] 13< C NMR (76 MHz, CDCl 3 ) δ 63.09, 32.82, 31.92, 29.67, 29.64, 29.62, 29.61, 29.45, 29.35, 25.75, 22.69, 14.11. 1,4-phenylenedimethanol, 2c

[0130] 1< H NMR (301 MHz, CDCl 3 ) δ 7.37 (s, 4H), 4.70 (s, 4H), 1.64 (s, 2H). 13< C NMR (76 MHz, CDCl 3 ) δ 127.25, 88.96. Furan-2-ylmethanol, 2d

[0131] 1< H NMR (301 MHz, CDCl 3 ) δ 7.39 (s, 1H), 6.31 (d, J = 15.0 Hz, 2H), 4.58 (s, 2H), 2.27 (s, 1H). 13< C NMR(76 MHz, CDCl 3 ) δ 154.03, 142.57, 110.36, 107.76, 57.42. Pentane-1,4-diol, 2e

[0132] 1< H NMR (301 MHz, CDCl 3 ) δ 3.94 - 3.78 (m, 1H), 3.77 - 3.58 (m, 2H), 2.72 (s, 2H), 1.76 - 1.39 (m, 4H), 1.21 (d, J = 6.2 Hz, 3H).

[0133] 13< C NMR (76 MHz, CDCl 3 ) δ 67.95, 62.89, 36.26, 29.14, 23.60.

Claims

1. A method for hydrogenating an ester of the general formula (III) in which the radicals Ra and Rb are each independently a carbon-containing organic, linear or branched, noncyclic or cyclic, saturated or unsaturated, aliphatic, aromatic or araliphatic radical which is unsubstituted or interrupted or substituted by heteroatoms or functional groups and has a molar mass of 15 to 10 000 g / mol, wherein the two radicals Ra and Rb may also be bonded to each other, with molecular hydrogen to give the alcohols at a temperature of 50 to 200°C and a pressure of 0.1 to 20 MPa abs in the presence of a manganese(I) complex, in which the manganese complex comprises a tridentate ligand L of the general formula (II) and comprises at least two carbonyl ligands, wherein R1, R2 are each independently an aliphatic hydrocarbon radical having 1 to 8 carbon atoms, an aromatic hydrocarbon radical having 6 or 10 carbon atoms or an araliphatic hydrocarbon radical having 7 to 12 carbon atoms, where the hydrocarbon radicals specified are unsubstituted or substituted by 1 to 3 methoxy, thiomethoxy or dimethylamino groups, and the two radicals R1 and R2 may also be bonded to each other to form a 5-to 10-membered ring including the phosphorus atom, R3, R4, R5, R6, R10, R11 are each independently hydrogen, linear C1 to C4-alkyl, branched C3 to C4-alkyl, methoxy, hydroxyl, trifluoromethyl, nitrile or dialkylamino each independently having 1 to 4 carbon atoms per alkyl group, R7, R8, R9 are each independently hydrogen, linear C1 to C4-alkyl or branched C3 to C4-alkyl, n, m are each independently 0 or 1, and the solid-dashed double lines are a single or double bond, with the proviso that in the case of n = 1, both solid-dashed double lines are a single bond and m is 1, and in the case of n = 0, one solid-dashed double line is a single bond and the other solid-dashed double line is a double bond, wherein, in the case of a double bond on the side facing the phenyl ring m = 1, in the case of a double bond on the side facing the pyridyl ring m = 0, or both solid-dashed double lines are a single bond and m equals 1.

2. The method according to claim 1, wherein the manganese complex has the general formula (I)         [Mn(L)(CO)2+nX1-n] Z(n)     (I) wherein X is an anionic monodentate ligand having a charge of "-1" Z is an anionic counterion having a charge of "-1" n is 0 or 1.

3. The method according to claims 1 and 2, wherein a molar ratio between the ester and the manganese (I) complex I of 100 to 100 000 is used.

4. The method according to claims 1 to 3, wherein the reaction is carried out in the presence of a base as cocatalyst.

5. The method according to claims 1 to 4, wherein the ester III used is sclareolide, which is hydrogenated to the corresponding diol.

6. A method for producing (-) Ambrox, wherein sclareolide is hydrogenated to Ambrox-1,4-diol in a first step (i) according to claim 5, and the resulting Ambrox-1,4-diol is cyclized to (-) Ambrox in a second step (ii).