Process for the preparation of 1-carbapenems and intermediates via silyl-substituted dithioacetals

Claim 1

A process for preparing ##STR217## wherein: R 6 , R 7 and R 8 are independently selected from the group consisting of: hydrogen; substituted and unsubstituted: alkyl, alkenyl, and alkynyl, having from 1-10 carbon atoms; cycloalkyl, cycloalkylalkyl, and alkylcycloalkyl, having 3-6 carbon atoms in the cycloalkyl ring and 1-6 carbon atoms in the alkyl moieties; phenyl; aralkyl, aralkenyl, and aralkynyl wherein the aryl moiety is phenyl and the aliphatic portion has 1-6 carbon atoms; wherein the substituent or substituents relative to the above-named radicals are selected from the group consisting of: ##STR218## wherein, relative to the above listed substituents on R 8 , R 6 and R 7 , the groups R 1 and R 2 are independently selected from: hydrogen, alkyl, alkenyl, and alkynyl, having from 1-10 carbon atoms; cycloalkyl, cycloalkylalkyl, and alkylcycloalkyl, having 3-6 carbon atoms in the cycloalkyl ring and 1-6 carbon atoms in the alkyl moieties; phenyl; aralkyl, aralkenyl, and aralkynyl wherein the aryl moiety is phenyl and the aliphatic portion has 1-6 carbon atoms; when R 6 /R 7 is hydrogen, then R 7 /R 6 is not ##STR219## when R 8 is CH 2 CH 2 NH 2 ; which process comprises the steps of oxidizing: ##STR220## wherein R 1' is hydrogen or a triorganosilyl or 3,4-dimethoxybenzyl protecting group; and R c is independently selected from alkyl having 1-6 carbon atoms and phenyl; followed by treating with 1,1'-carbonyl-dimidazole followed by R 2' O 2 CCH 2 CO 2 ) 2 Mg to yield: ##STR221## wherein R 2' is a protecting group selected from p-nitrobenzyl or benzyl; followed by hydrolysis to yield: ##STR222## followed by treating with a diazotizing agent selected from p-carboxybenzenesulfonylazide, toluene sulfonylazide, methanesulfonylazide, toluenesulfonylazide, and methanesulfonylazide to yield: ##STR223## followed by cyclizing in the presence of a catalyst selected from bis(acetylacetonato)Cu (II), CuSO 4 , Cu powder, ##STR224## to yield: ##STR225## Followed by activating by treating with an acylating agent selected from p-toluenesulfonic acid anhydride, p-nitrophenylsulfonic acid anhydride, 2,4,6-triisopropylphenylsulfonic acid anhydride, methanesulfonic acid anhydride, trifluoromethane sulfonic acid anhydride, diphenyl chlorophosphate, toluenesulfonyl chloride, and p-bromophenylsulfonyl chloride; followed by reacting with HSR 8 and deblocking.