Method for constructing quaternary carbon on oxazolone with carbonyl alpha position substituted by alkyl

Abstract

The invention relates to a method for constructing quaternary carbon on oxazolone with carbonyl alpha site substituted by alkyl. Specifically, the obtained quaternary carbon amino acid can be obtained through simple ring opening of an oxazolone compound under an acidic condition. The method comprises the following steps: reacting 2-alkyl oxazolone with isoprene under the action of diphosphine ligand and acid to obtain a product with carbonyl alpha carbon of 2-alkyl oxazolone as quaternary carbon. A series of quaternary carbon oxazolone derivatives are obtained through simple and safe steps.

Description

Technical Field

[0001] The invention relates to a method for constructing a quaternary carbon on an oxazolone in which the α position of the carbonyl group is substituted by an alkyl group. Background Art

[0002] α-quaternary amino acids play an important role in peptide modification, because the α-quaternary carbon center can restrict conformational flexibility to improve pharmacokinetic properties. Therefore, the rapid assembly of α-quaternary amino acids has become a frontier in organic synthesis. At present, allylation reactions with three structures as basic skeletons, amino acid esters, imino esters and azlactones, have been developed to construct a variety of allylic amino acid ester derivatives. Oxazolone is a universal precursor for the synthesis of tetrasubstituted amino acids, and its prenylation reaction is an important strategy for the construction of α-quaternary amino acids. Oxazolone can be regarded as an effective amino acid precursor in organic synthesis, and quaternary carbon is constructed on oxazolone with alkyl substitution at the α position of the carbonyl group by transition metal catalysis. Oxazolone can be opened in one step under acidic or alkaline conditions to obtain amino acids or amino acid esters, respectively, and is a good amino acid precursor.

[0003] Based on this, we report a method for constructing quaternary carbon on oxazolone with alkyl substituted α to carbonyl. The reaction is mainly through the oxidative addition of the enol isomerization product of oxazolone with metal hydride, direct insertion of isoprene, and conversion to π-isopentenyl metal species, followed by the nucleophilic attack of oxazolone controlled by the steric hindrance of the ligand and the environment to provide quaternary carbon oxazolone products. This method can be used to construct a series of quaternary carbon oxazolone derivatives with alkyl substituted α to carbonyl. The reaction scheme does not produce equivalent by-products and has excellent regioselectivity, broad functional group tolerance and mild reaction conditions.

[0004] Compared with the traditional method for obtaining 2-quaternary carbon oxazolone, the raw materials used in the present invention are cheap and easy to obtain, the conditions are mild and easy to operate, the target product can be obtained in one step, and the product has excellent regional selectivity, providing a new method for the diversity of drug molecules.

[0005] In summary, this paper describes a simple, mild method for obtaining quaternary carbonyl oxazolone substituted with an alkyl group at the alpha position of the carbonyl group. Summary of the invention

[0006] The object of the present invention is to provide a method for preparing a quaternary carbonyl oxazolone substituted with an alkyl group at the α position of the carbonyl group.

[0007]

[0008] Reaction equation 1: Method for constructing a quaternary carbon on an oxazolone with an alkyl group substituted at the α position of the carbonyl group

[0009] The specific steps are as follows:

[0010] Under the protection of an inert atmosphere, a palladium catalyst, a bisphosphine ligand, oxazolone, isoprene, an acid and a solvent are added in sequence, and the reaction is carried out at 40-80° C. for 12-24 hours. After the reaction is completed, an isopentenyl oxazolone derivative is separated.

[0011] The oxazolone compound includes 2-alkyl oxazolone, and the specific structure is one or more of the following structural formulas:

[0012]

[0013] The preferred molar ratio of oxazolone to isoprene is 1.0:3.0.

[0014] The palladium catalyst used is bis(tri-tert-butylphosphine)palladium, and the amount of the palladium catalyst used is 1-20% molar equivalent (relative to the oxazolone compound), preferably 5-10% molar equivalent.

[0015] The acid is one or more of benzoic acid, phenylboric acid, p-toluenesulfonic acid, citric acid, p-trifluoromethylbenzoic acid, and 2,6-difluorobenzoic acid; preferably 2,6-difluorobenzoic acid; the amount of the additive is 10-50% molar equivalent (relative to the oxazolone compound), preferably 10-20% molar equivalent.

[0016] The solvent is changed to one or more of toluene, n-hexane, dichloromethane, nitrogen methyl pyrrolidone, tetrahydrofuran, 1,4-dioxane, and ethyl acetate; preferably one or more of toluene and n-hexane. The amount of the solvent is 0.2-2.0 mL, preferably 0.5-1.0 mL, per mmol of the oxazolone compound.

[0017] The ligand is a bisphosphine ligand, including one or more of the compounds represented by the following structures L1, L2, L3, L4, L5, L6, L7, and L8; preferably L1; the amount of the bis-ligand is 1-20% molar equivalent (relative to the oxazolone compound), preferably 5-10% molar equivalent;

[0018]

[0019] The present invention has the following advantages:

[0020] First, the reaction raw materials, oxazolone and isoprene, are simple and easily available. Second, the reaction conditions are mild and safe, and the reaction steps are simple and efficient. Finally, the obtained product is a novel quaternary carbon oxazolone with an alkyl substituted at the α position of the carbonyl group, with excellent yield and selectivity. DETAILED DESCRIPTION

[0021] In order to better understand the present invention, the following examples are used for illustration. The reaction materials and results of Examples 1-17 are shown in Table 1. 3a is a known product.

[0022] Table 1 Reaction results of different oxazolone compounds

[0023]

[0024]

[0025]

[0026]

[0027] It can be seen from the results in Table 1 that different oxazolones can be converted into isopentenyl oxazolone derivatives with medium to high yields and high regioselectivity under the catalysis of palladium with isoprene.

[0028] Example 1

[0029] Palladium catalyst Pd(P t Bu3)2 (0.005mmol, bis(tri-tert-butylphosphine)palladium), bisphosphine ligand L1 (0.005mmol), tert-butanol (0.2mL), stirred at 40°C for 15 minutes; 2,6-difluorobenzoic acid (0.02mmol), oxazolone 1a (0.20mmol), isoprene (0.60mmol) were added to the reactor, and the reaction was carried out at 40°C for 24 hours; after the reaction, the oxazolone isopentenylated derivative 3a was separated by column chromatography in a yield of 89%, and the compound was identified by nuclear magnetic resonance (hydrogen spectrum, carbon spectrum and fluorine spectrum) and high-resolution mass spectrometry.

[0030] The test data are as follows:

[0031] NMR(400MHz,Chloroform-d)δ8.02–7.96(m,2H),7.61–7.53(m,1H),7.52–7.44(m,2H),5.08–4.99(m,1H),2.64–2.49(m,2H),1.63(s,6H),1.53(s,3H). 13 HRMS calculated for C 15 H 18 NO2[M+H] + 244.1332, found 244.1332.

[0032] Example 2

[0033] The operation process and conditions were the same as those in Example 1, except that the oxazolone compound described in Table 1 was different. The yield of product 3b was 84%, and the structure of the compound was identified by NMR (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrometry.

[0034] Chloroform-d)δ8.02–7.97(m,2H),7.59–7.54(m,1H),7.51–7.46(m,2H),5.05–4.98(m,1H),2.57(d,J= 7.7Hz,2H),1.98–1.83(m,2H),1.63(s,6H),1.38–1.24(m,1H),1.24–1.11(m,1H),0.90(t,J=7.3Hz,3H). 13 HRMScalculated for C 17 H 22 NO2[M+H] + 272.1645, found 272.1648.

[0035] Example 3

[0036] The operation process and conditions were the same as those in Example 1, except that the oxazolone compound described in Table 1 was different. The yield of product 3c was 92%, and the structure of the compound was identified by NMR (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrometry.

[0037] Chloroform-d)δ8.07–7.85(m,2H),7.62–7.53(m,1H),7.52–7.40(m,2H),5.04–4.83(m,1H),2.55(d,J=7.6Hz,2H),1 .98(dd,J=14.1,5.3Hz,1H),1.83(dd,J=14.1,7.6Hz,1H),1.61(s,6H),0.90(d,J=6.7Hz,3H),0.85(d,J=6.6Hz,3H). 13HRMS calculated for C 18 H 24 NO2[M+H] + 286.1802, found 286.1802.

[0038] Example 4

[0039] The operation process and conditions were the same as those in Example 1, except that the oxazolone compound described in Table 1 was different. The yield of product 3d was 88%, and the structure of the compound was identified by NMR (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrometry.

[0040] Chloroform-d)δ7.87–7.79(m,2H),7.54–7.46(m,1H),7.44–7.36(m,2H),7.22–7.07(m,5H),5.10–4.95(m,1 H),3.29–3.12(m,2H),2.73(dd,J=14.2,8.0Hz,1H),2.65(dd,J=14.2,7.1Hz,1H),1.65(s,3H),1.63(s,3H). 13 CNMR(100MHz,Chloroform-d)δ179.7,159.8,137.6,134.7,132.5,130.2,128.7,128.2,127.9,127.2,126.0,116.3,75.4,43.2,36.2,26.1,18.3.HRMS calculated for C 21 H 22 NO2[M+H] + 320.1645, found 320.1646.

[0041] Example 5

[0042] The operation process and conditions were the same as those in Example 1, except that the oxazolone compound described in Table 1 was different. The yield of the product 3e was 82%, and the structure of the compound was identified by NMR (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrometry.

[0043] (400MHz,Chloroform-d)δ8.03–7.96(m,2H),7.61–7.55(m,1H),7.52–7.46(m,2H),5.06–4.97(m,1H),2 .58(d,J=7.6Hz,2H),2.52–2.44(m,1H),2.42–2.34(m,1H),2.29–2.20(m,2H),2.05(s,3H),1.63(s,6H). 13 HRMScalculated for C 17 H 22 NO2S[M+H] + 304.1366, found 304.1368.

[0044] Example 6

[0045] The operation process and conditions were the same as those in Example 1, except that the oxazolone compound described in Table 1 was different. The yield of the product 3f was 99%, and the structure of the compound was identified by NMR (hydrogen spectrum, carbon spectrum and fluorine spectrum) and high-resolution mass spectrometry.

[0046] Chloroform-d)δ8.03–7.97(m,2H),7.59–7.53(m,1H),7.51–7.43(m,2H),5.00–4.92(m, 1H),2.66–2.54(m,2H),1.96–1.65(m,6H),1.61(s,3H),1.60(s,3H),1.33–1.08(m,5H). 13 CNMR(100MHz,Chloroform-d)δ180.4,159.7,137.3,132.5,128.8,128.0,126.2,116.3,77.4,44.1,33.4,27.2,27.0,26.4,26.2,26.1,26.0,18.2.HRMS calculated for C 20 H 26 NO2[M+H] + 312.1958, found 312.1958.

[0047] Example 7

[0048] The operation process and conditions are the same as those of Example 1. The difference from Example 1 is that the oxazolone compound described in Table 1 is different. The yield of the product 3g is 98%. The structure of the compound is identified by nuclear magnetic resonance (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrometry.

[0049] 3g(m,2H),7.74–7.67(m,1H),7.47–7.40(m,1H),7.37–7.28(m,2H),7.18–7.12(m,1H),7.10–7.00(m,2H),6.96(d,J=2.4Hz,1H) ,5.12–5.01(m,1H),3.36(d,J=2.3Hz,2H),2.79(dd,J=14.3,8.2Hz,1H),2.71(dd,J=14.3,6.9Hz,1H),1.64(s,3H),1.62(s,3H). 13 CNMR(100MHz,Chloroform-d)δ180.2,159.9,137.3,135.8,132.4,128.6,127.9,127.7,126.0, 123.8,121.9,119.7,119.5,116.5,110.9,109.2,75.9,35.9,33.0,26.0,18.3.HRMScalculated for C 23 H 23 N2O2[M+H] + 359.1754, found 359.1755.

[0050] Example 8

[0051] The operation process and conditions are the same as those in Example 1. The difference from Example 1 is that the oxazolone compound described in Table 1 is different. The yield of the product 3h is 78%. The structure of the compound is identified by nuclear magnetic resonance (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrometry.

[0052] =18 / 1), purified by column chromatography(petroleum ether / ethyl acetate=30 / 1). NMR data for main isomer 4i was provided. 1H NMR(400MHz,Chloroform-d)δ7.57(dt,J=7.8,1.3Hz,1H),7.52–7.48(m,1H),7.38(t,J=8.0Hz,1H ),7.14–7.08(m,1H),5.09–4.97(m,1H),3.87(s,3H),2.64–2.49(m,2H),1.64(s,6H),1.53(s,3H). 13 HRMS calculated for C 16 H 20 O3[M+H] + 274.1438, found 274.1439.

[0053] Example 9

[0054] The operation process and conditions were the same as those in Example 1, except that the oxazolone compound described in Table 1 was different. The yield of product 3i was 87%, and the structure of the compound was identified by NMR (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrometry.

[0055] procedure B, colorless oil, 44.5mg, 87% yield; purified by column chromatography (petroleum ether / ethyl acetate=30 / 1). 1 H NMR (400MHz, Chloroform-d) δ7.91–7.84(m,2H),7.28(d,J=8.1Hz,2H),5.09–4.97(m,1H),2.63–2.48(m,2H),2.42(s,3H),1.63(s,6H),1.52(s,3H). 13 HRMS calculated for C 16 H 20 NO2[M+H] +258.1489, found 258.1490.

[0056] Example 10

[0057] The operation process and conditions were the same as those in Example 1, except that the oxazolone compound described in Table 1 was different. The yield of product 3j was 89%, and the structure of the compound was identified by NMR (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrometry.

[0058] NMR(400MHz,Chloroform-d)δ7.83(s,1H),7.80–7.72(m,1H),7.41–7.34(m,2H) ),5.07–4.99(m,1H),2.64–2.49(m,2H),2.42(s,3H),1.64(s,6H),1.53(s,3H). 13 HRMS calculated for C 16 H 20 NO2[M+H] + 258.1489, found 258.1489.

[0059] Embodiment 11

[0060] The operation process and conditions were the same as those in Example 1, except that the oxazolone compound described in Table 1 was different. The yield of the product 3k was 72%, and the structure of the compound was identified by NMR (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrometry.

[0061] MHz,Chloroform-d)δ8.19–8.11(m,2H),8.08–8.03(m,2H),5.07–4.96(m,1H),3.96(s,3H),2.65–2.52(m,2H),1.63(s,6H),1.55(s,3H). 13 HRMScalculated for C 17 H 20NO4[M+H] + 302.1387, found 302.1387.

[0062] Example 12

[0063] The operation process and conditions are the same as those of Example 1. The difference from Example 1 is that the oxazolone compound described in Table 1 is different. The yield of product 31 is 68%. The structure of the compound is identified by nuclear magnetic resonance (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrometry.

[0064]

[0065] NMR(400MHz,Chloroform-d)δ7.94–7.84(m,1H),7.61–7.50(m,1H),7.31–7.24(m,1H ),7.25–7.18(m,1H),5.10–4.98(m,1H),2.68–2.52(m,2H),1.65(s,6H),1.56(s,3H). 13 CNMR(100MHz,Chloroform-d)δ180.3,161.4(d,J=260.5Hz),156.7(d,J=5.5Hz),137.8,134.2(d,J=8.8Hz) ,130.7,124.5(d,J=3.9Hz),117.2(d,J=21.2Hz),116.3,114.7(d,J=10.0Hz),70.2,37.0,26.1,23.2,18.2. 19 F NMR(375MHz,Chloroform-d)δ-108.6.HRMScalculated for C 15 H 17 FNO2[M+H] + 262.1238, found 262.1241.

[0066] Embodiment 13

[0067] The operation process and conditions were the same as those in Example 1, except that the oxazolone compound described in Table 1 was different. The yield of the product 3m was 73%, and the structure of the compound was identified by NMR (hydrogen spectrum, carbon spectrum and fluorine spectrum) and high-resolution mass spectrometry.

[0068]

[0069] Hz,1H),7.88–7.84(m,1H),7.57–7.51(m,1H),7.43(t,J=7.9Hz,1H),5.01(m,1H),2.63–2.50(m,2H),1.64(s,3H),1.64(s,3H),1.53(s,3H). 13 HRMS calculated for C 15 H 17 ClNO2[M+H] + 278.0942, found 278.0944.

[0070] Embodiment 14

[0071] The operation process and conditions were the same as those in Example 1, except that the oxazolone compound described in Table 1 was different. The yield of the product 3n was 63%, and the structure of the compound was identified by NMR (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrometry.

[0072]

[0073] by column chromatography(petroleum ether / ethyl acetate=30 / 1).1H NMR (400MHz, Chloroform-d) δ8.15–8.07(m,2H),7.78–7.73(m,2H),5.05–4.96(m,1H),2.67–2.51(m,2H),1.63(s,6H),1.55(s,3H). 13 C NMR(100MHz,Chloroform-d)δ180.2,158.7,138.0,134.3(q,J=32.5Hz),129.5,128 .4,125.9(q,J=3.9Hz),123.7(q,J=272.1Hz),116.1,70.7,37.0,26.0,23.2,18.2. 19 F NMR(375MHz,Chloroform-d)δ-63.2.HRMScalculated for C 16 H 17 F3NO2[M+H] +312.1206, found 312.1208.

[0074] Embodiment 15

[0075] The operation process and conditions were the same as those in Example 1. The difference from Example 1 was that, except for the oxazolone compound described in Table 1, the yield of product 3o was 69%, and the structure of the compound was identified by nuclear magnetic resonance (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrometry.

[0076] 30 / 1). 1 H NMR(400MHz,Chloroform-d)δ9.19(d,J=8.7Hz,1H),8.11(dd,J=7.3,1.3Hz,1H),8.02(d,J=8.2Hz,1H),7.91(d,J=8.1Hz ,1H),7.68–7.61(m,1H),7.59–7.50(m,2H),5.16–5.09(m,1H),2.73–2.60(m,2H),1.67(s,3H),1.65(s,3H),1.62(s,3H). 13 C NMR(100MHz,Chloroform-d)δ180.7,159.6,137.6,133.9,133.3,130.9,129.9,12 8.8,128.1,126.6,126.1,124.8,122.3,116.7,70.8,37.2,26.1,23.5,18.3.HRMS calculated forC 19 H 20 NO2[M+H] + 294.1489, found 294.1486.

[0077] Example 16

[0078] The operation process and conditions are the same as those of Example 1. The difference from Example 1 is that, in addition to the oxazolone compound described in Table 1, the yield of the product 3p is 60%, and the structure of the compound is identified by nuclear magnetic resonance (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrometry.

[0079] NMR (400MHz, Chloroform-d) δ7.66 (dd, J=1.8, 0.8Hz, 1H), 7.08 (dd, J=3.5, 0.8Hz, 1H), 6.58 (dd, J=3.5,1.8Hz,1H),5.09–5.00(m,1H),2.65–2.48(m,2H),1.66(s,3H),1.63(s,3H),1.52(s,3H).13 HRMS calculated for C 13 H 16 NO3[M+H] + 234.1125, found 234.1122.

[0080] Comparative Example 1

[0081] The raw materials, operation process and conditions were the same as those in Example 1, except that no palladium catalyst was added and product 3a was not obtained.

[0082] Comparative Example 2

[0083] The raw materials, operation process and conditions were the same as those in Example 1, except that ligand L1 was not added and product 3a was not obtained.

[0084] Comparative Example 3

[0085] The raw materials, operation process and conditions were the same as those in Example 1, except that the acid was replaced with propionic acid, and product 3a was obtained in a yield of 32%.

[0086] Comparative Example 4

[0087] The raw materials, operation process and conditions were the same as those in Example 1, except that the ligand was replaced with bis(2-diphenylphosphinophenyl) ether, and product 3a was obtained in a yield of 41%.

[0088] Comparative Example 5

[0089] The raw materials, operation process and conditions were the same as those in Example 1, except that the ligand was replaced by PPhCy2, and product 3a was obtained in a yield of 3%.

[0090] Comparative Example 6

[0091] The raw materials, operating procedures and conditions were the same as those in Example 1, except that the palladium catalyst was replaced with palladium acetate, and product 3a was not obtained.

Claims

1. A method for constructing a quaternary carbon on an oxazolone substituted with an alkyl group at the alpha position of the carbonyl group, Features: The alkyl oxazolone 1 and isoprene 2 shown in the following formula are used as raw materials to generate oxazolone 3 in which the carbonyl α carbon is a quaternary carbon, and the reaction formula is as follows: Wherein, 2-alkyloxazolone 1 includes one or more alkyloxazolone derivatives; the substituent R 1 Ph, 2-OMeC 6 H 4 , 3-OMeC 6 H 4 、4-MeC 6 H 4 、2-FC 6 H 4 、3-ClC 6 H 4 , 4-CF 3 C 6 H 4 、3-MeC 6 H 4 , 2-Naphth, 2-furyl, 4-COOMe, one or more thereof; R 2 For Me, i Bu, n One or more of Pr, Bn, Cy, EtSMe, (1H-indol-3-yl)methyl; Oxazolone and isoprene are reacted in a solvent in the presence of bis(tri-tert-butylphosphine)palladium and a bisphosphine ligand, with or without adding an acid to the reaction system to generate an oxazolone derivative in which the carbonyl alpha carbon is a quaternary carbon; The bisphosphine ligand includes one or more of the compounds represented by the following structures L1, L2, L3, L4, L5, L6, L7, and L8; preferably L1; 2. The method according to claim 1, Features: Wherein oxazolone is one or more of the following structural formulas:

3. The method according to claim 1, Features: The specific steps are as follows: The reaction is carried out in a reactor under the protection of an inert atmosphere, and a palladium catalyst bis(tri-tert-butylphosphine)palladium, a bisphosphine ligand and a solvent are added to the reactor, and stirred at 20-60° C. (preferably 30-45° C.) for 10-30 minutes (preferably 15-20 minutes); then oxazolone and isoprene are added to the reactor, and the reaction is carried out at 30-90° C. (preferably 40-80° C.) for 12-24 hours (preferably 16-24 hours); after the reaction is completed, an oxazolone derivative in which the carbonyl α carbon is a quaternary carbon is obtained by separation.

4. The method according to claim 1, 2 or 3, Features: The molar ratio of oxazolone to isoprene is (1.0:1.0-1.0:5.0), preferably 1.0:3.0; The amount of the biligand used is 2-20 mol%, preferably 5-10 mol%, of the oxazolone compound.

5. The method according to claim 1, 2 or 3, Features: The palladium catalyst used is bis(tri-tert-butylphosphine)palladium, and the amount of the palladium catalyst used is 1-20 mol%, preferably 5-10 mol%, of the oxazolone compound.

6. The method according to claim 1, 2 or 3, Features: The acid is one or more of benzoic acid, phenylboric acid, p-toluenesulfonic acid, citric acid, p-trifluoromethylbenzoic acid, and 2,6-difluorobenzoic acid; preferably 2,6-difluorobenzoic acid; The amount of the acid used is 10-50 mol%, preferably 10-20 mol%, based on the oxazolone compound.

7. The method according to claim 1, 2 or 3, Features: The solvent is one or more of toluene, n-hexane, dichloromethane, nitrogen methyl pyrrolidone, tetrahydrofuran, 1,4-dioxane, ethyl acetate, and tert-butanol; preferably one or more of toluene and n-hexane; The amount of solvent used is 0.2-2.0 mL, preferably 0.5-1.0 mL, per mmol of oxazolone compound; The inert gas is one or both of argon and nitrogen.

8. The method according to claim 1, 2 or 3, Features: The amount of the biligand used is 2-20 mol%, preferably 5-10%, of the oxazolone compound.

9. The method according to any one of claims 1 to 8, Features: The structural formula of oxazolone with carbonyl α carbon as quaternary carbon is as follows: Wherein, 2-alkyloxazolone 1 includes one or more alkyloxazolone derivatives; the substituent R 1 Ph, 2-OMeC 6 H 4 , 3-OMeC 6 H 4 、4-MeC 6 H 4 、2-FC 6 H 4 、3-ClC 6 H 4 , 4-CF 3 C 6 H 4 、3-MeC 6 H 4 , 2-Naphth, 2-furyl, 4-COOMe or two thereof; R 2 For Me, i Bu, n One or more of Pr, Bn, Cy, EtSMe, (1H-indol-3-yl)methyl, etc.

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