Process for Enantioselective Synthesis of individual Enantiomers of arilmetansulfinilo tiosustituidos derivatives by Asymmetric oxidation

摘要

1. A method for manufacturing sulfur oxide compound (1) in formula, either as a separate counterpart or in a corresponding Enrichment Form: u, V and W are selected independently from a link, CH2, cr2324, O, s (o) and, N11, C (= O),CHOH, CHOR14, C = NOR14 or C = NNR12R13; rings A, B and C are optionally substituted with 1 to 3 groups selected from H, F, Cl, Br, I, OR22, NR23R24, NHOH, NO2, CN, CF3, C1-6 alkyl, C2-6 alkenyl, alkynyl C2-6, C3-7 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5- or 6 membered heteroaryl, arylalkyl, C (= O) R22, CO2R22, OC (= O) R22, C (= O) NR23R24, NR21C (= O) R22, NR21CO2R22, OC (= O) NR23R24 and NR21C (= S) R22; ring D is optionally substituted with a group selected from C 1-6 alkyl, 5-10 membered phenyl heteroaryl; X is a bond, O, NR11, OC (R22) 2, C (R22) 2O, C (R22) 2NR21, NR21C (R22) 2, C (= O) NR21, NR21C (= O),S (O) 2, S (O) 2NR22, NR22S (O) 2, C (R22) 2C (R22) 2, CR21 = CR21, C ::: C; R2 is selected from H, F, Cl, Br, I, OR16, NR17R18, NHOH, NO2, CN, CF3, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C (= O ) R16, CO2R16, OC (= O) R16, C (= O) NR17R18, NR15C (= O) R16, NR15CO2R16, OC (= O) NR17R18 and NR15C (= S) R16; alternatively, two R2 groups may be combined to form a methylenedioxy, ethylenedioxy, or propylenedioxy group; Ar1 is C6-10 aryl optionally substituted with 0-5 R3; C5-10 cycloalkyl optionally substituted with 0-5 R3; C5-10 heteroaryl group optionally substituted with 0-5 R3; wherein said heteroaryl comprises 1, 2 or 3 heteroatoms selected from N, O, S or Se,where: R3 is selected from H, F, Cl, Br, I, OR16, OCF3, NR17R18, NHOH, NO2, CN, CF3, CH2OR16, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3 cycloalkyl -7, 3-7-membered heterocycloalkyl, phenyl, 5- or 6-membered heteroaryl, arylalkyl C7-10, C (= O) R16, CO2R16, OC (= O) R16, C (= O) NR17R18, NR15C (= O) R16, NR15CO2R16, OC (= O) NR17R18, NR15C (= S) R16 and NR15S (= O) 2R16; alternatively, two R3 groups may be combined to form a methylenedioxy, ethylenedioxy, or propylenedioxy group; Y is C1-6 alkylene; R1 is selected from CN, C (= O) R14, CO2R11, C (= O) NR12R13, C (= O) NR21OR22, C (= NR11) R12R13, OC (= O) R11, OC (= O) NR12R13, NR12R13, NR21NR12R13, NR21C (= O) R14, NR21C (= O) NR12R13,Nr21s (o) 2r11, nr21s (o) 2nr12r13; R11 is independently selected from h, C1-6, c3-7, arilo C6-10 and arilalquilo in each case; in these cases, these tar layers, arilo and arilalquilo can be replaced by 1 to 3 R20 groups; in each case, R12 and R13 are independently selected, Among them, C1-6, arilo C6-10, nr23r24 or R12 and R13, together with the N atoms they connect, form a heterocyclic ring composed of 3 to 7 members; in these heterocyclic ring structures, one to three R20 groups can be selected to replace; in each form, R14 is selected separately.Among the three asphalt groups, C1-6, arilo C6-10 and arilalquilo, the alternative asphalt, arilo and arilalquilo groups, R15 in each representation is independently selected from h, C1-6, R16 and C6-10. Among these categories, you can choose to replace these renters and arilo categories with 1 to 3 R20 categories; in each case, choose R17 and R18 categories respectively,H, C1-6 alkyl and C6-10 aryl or R17 and R18, together with the N to which they are attached, form a 3-7 membered heterocyclic ring; wherein said alkyl and aryl groups and heterocyclic ring are optionally substituted with 1 to 2 oxo groups; R20 at each occurrence is independently selected from F, Cl, Br, I, OR22, NR23R24, NHOH, No2, CN, CF3, C1-6 alkyl optionally substituted with 1 to 3 OH, C2-6 alkenyl, alkynyl C2-6, C3-7 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl substituted by 0 to 1 OR25, 5-6 membered heteroaryl, arylalkyl, = O, C (= O) R22, CO2R22, OC (= O) R22 , C (= O) NR23R24, NR21C (= O) R2, NR21CO2R22, and OC (= O) NR23R24;In each case, R21 is independently selected from H and C1-6 tar; in each case, R22 is independently selected from h, C1-6 tar, c1-6-oh and arilo C6-10; in each case, R23 and R24 are independently selected from h, C1-6 and arilo C6-10, or R23 and R24. Together with the attached n, they form a heterocyclic cyclic cyclic ring composed of 3-7 substitute members, which is replaced by 1-3 oxo groups; in each case, R25 is independent of the selection of H, F, Cl, Br, C1-6 tar and C1-6 tar; X is 1, 2, 3 or 4; it is 0, 1 or 2; it includes (a) contacting a productive sulfur. Formula (2) where AR,Y and R1, as defined above, have a metal chiral binding, an oxidant in the substrate and an organic solvent, and alternative (b) separates the sulfur oxide (1) from the formula. In this method, a formula sulfur oxide compound (1) is obtained by at least 80% dwarfism excess,95% or 99%. Sulfoxide compound of formula (1) selected from (-) or (+) - 2- [2- (4-chlorophenyl) benzyl] sulfinylacetamide; (-) or (+) - 2 - [([1,1'-biphenyl] -2-ylmethyl) sulfinyl] acetamide; and (-) or (+) - 2- [2- (3,4-dichlorophenoxy) -benzyl] sulfinylacetamide.