title: Diastereo- and enantioselective cyclopropanation with chromium fischer carbene complexes: alkenyl oxazolines as useful achiral and chiral substrates.
abstract: 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.
authors.affiliation: Instituto Universitario de Química Organometálica Enrique Moles, and Departamento de Química Física y Analítica, Universidad de Oviedo, Avda. Julián Clavería 8, 33071 Oviedo, Spain. barluenga@sauron.quimica.uniovi.es
authors.forename: J
authors.initials: J
authors.lastname: Barluenga
authors.forename: A L
authors.initials: AL
authors.lastname: Suárez-Sobrino
authors.forename: M
authors.initials: M
authors.lastname: Tomás
authors.forename: S
authors.initials: S
authors.lastname: García-Granda
authors.forename: R
authors.initials: R
authors.lastname: Santiago-García