Indium-mediated asymmetric barbier-type allylations: additions to aldehydes and ketones and mechanistic investigation of the organoindium reagents.
We report a simple, efficient, and general method for the indium-mediated enantioselective allylation of aromatic and aliphatic aldehydes and ketones under Barbier-type conditions in a one-pot synthesis affording the corresponding chiral alcohol products in very good yield (up to 99%) and enantiomeric excess (up to 93%). Our method is able to tolerate various functional groups, such as esters, nitriles, and phenols. Additionally, more substituted allyl bromides, such as crotyl and cinnamyl bromide, can be used providing moderate enantioselectivity (72% and 56%, respectively) and excellent diastereoselectivity when employing cinnamyl bromide (>95/5 anti/syn). However, the distereoselectivity when using crotyl bromide was poor and other functionalized allyl bromides under our method afforded low enantioselectivities for the alcohol products. In these types of indium-mediated additions, solvent plays a major role in determining the nature of the organoindium intermediate and we observed the susceptibility of some allylindium intermediates to hydrolysis in protic solvents. Under our reaction conditions using a polar aprotic solvent, we suggest that an allylindium(III) species is the active allylating intermediate. In addition, we have observed the presence of a shiny, indium(0) nugget throughout the reaction, irrespective of the stoichiometry, indicating disproportionation of indium halide byproduct formed during the reaction.
Haddad
Terra D
TD
Department of Chemistry and Biochemistry, University of California Santa Cruz, 1156 High Street, Santa Cruz, California 95064, USA.
Hirayama
Lacie C
LC
Singaram
Bakthan
B
D000447:Aldehydes / Q000737:chemistry*; D000475:Alkenes / Q000737:chemistry*; D000498:Allyl Compounds / Q000737:chemistry*; D002384:Catalysis; D003432:Cross-Linking Reagents; D007202:Indicators and Reagents; D007204:Indium / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000447:Aldehydes; D000475:Alkenes; D000498:Allyl Compounds; D003432:Cross-Linking Reagents; D007202:Indicators and Reagents; D007659:Ketones; D009942:Organometallic Compounds; D007204:Indium; C050431:allyl bromide