Diastereo- and enantioselective cyclopropanation with chromium Fischer carbene complexes: Alkenyl oxazolines as useful achiral and chiral substrates

The cyclopropanation reaction of chromium Fischer carbene complexes with al kenyl oxazolines has been studied in both racemic and enantioselective fash ions. The oxazolinyl group acts as both electron-acceptor substituent and c hiral auxiliary. Achiral (4,4-dimethyloxazolin-2-yl)alkenes derived from tr ans-crotonic and trans-cinnamic acids 2a,b undergo the cyclopropanation rea ction to give 4a-d,g with excellent diastereoselectivity (trans/cis ratio b etween 93:7 and >97:3), while those derived from acrylic and metacrylic aci ds 2c,d give the cyclopropanes 4e,f,h with much lower selectivity (trans/ci s ratio between 68:32 and 83:17). The homogeneous catalytic hydrogenolysis of 4 leads in a selective manner to 5 or 6, depending on the nature of the R-3 substituent. The removal of the oxazoline moiety is achieved by carboxy benzylation/hydrolysis and ester reduction, yielding monoprotected 1,4- and 1,3-diols 9 and 11, respectively. The alkenes derived from enantiopure (S) -valinol and (S)-tert-leucinol 3 led to cyclopropanes trans-12 with high re lative and absolute stereocontrol. Using tert-leucinol as the auxiliary per mits attaining total facial stereoselectivity (>98% ee). Reductive cleavage of the cyclopropane ring and removal of the auxiliary afford the enriched alcohols (3S,4S)-9 and (S)-11. The stereochemical outcome of the cyclopropa nation reaction is rationalized by a trans approach of the s-cis conformer of the alkenyl oxazoline to the carbene complex involving the less hindered face of the oxazoline auxiliary and the re-face of the carbene complex.