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 alkenyl oxazolines
has been studied in both racemic and enantioselective fashions. The oxazolinyl group acts as both electron-acceptor substituent and chiral auxiliary. Achiral (4,4-dimethyloxazolin-2-yl)alkenes derived from trans-crotonic
and trans-cinnamic acids 2a,b undergo the cyclopropanation reaction to give 4a−d,g with excellent
diastereoselectivity (trans/cis ratio between 93:7 and >97:3), while those derived from acrylic and metacrylic
acids 2c,d give the cyclopropanes 4e,f,h with much lower selectivity (trans/cis 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 R3 substituent. The removal of the oxazoline moiety is achieved by carboxybenzylation/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 relative and absolute
stereocontrol. Using tert-leucinol as the auxiliary permits 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 cyclopropanation 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.