US EPA

4080485 

Journal Article 

Origin of syn/anti diastereoselectivity in aldehyde and ketone crotylation reactions: a combined theoretical and experimental study 

Tietze, LF; Kinzel, T; Schmatz, S 

2006 

Yes 

Journal of the American Chemical Society
ISSN: 0002-7863
EISSN: 1520-5126 

128 

35 

11483-11495 

English 

16939272 

10.1021/ja062528v 

WOS:000240116300042 

http://://WOS:000240116300042
Exit
 

We report on experimentally determined and computationally predicted diastereoselectivities of (a) multicomponent crotylation (MCC) reactions of simple aliphatic aldehydes and ketones and (b) of acetal substitution (AS) reactions of aldehyde dimethyl acetals with E- and Z-configurated crotyl trimethylsilane to give homoallylic methyl ethers bearing two newly formed stereogenic centers. We found that corresponding MCC and AS reactions give nearly equal syn/anti ratios. While the crotylations of acetaldehyde and propionaldehyde mainly result in the syn product for E-configurated silane and in the anti product for Z-configurated silane, the syn product is found as main product for the crotylation of pivaldehyde regardless of substrate double bond geometry. Using butanone as substrate, the anti product is found as main product in both cases. By computational investigation employing the B3LYP/6-31+G(d) level of theory in dichloromethane solution (PCM/UAKS), we found that the attack of O-methyl-substituted carboxenium ions by crotyl silane explains the experimentally observed selectivities, indicating that these crotylations in fact proceed in an S(N)1-type reaction via this ionic intermediate. Comparison of relevant open transition-state structures leads to a rationalization of the observed selectivities. For all systems studied, three transition-state conformations are necessary and sufficient to determine the selectivity. This has been confirmed by studying the MCC reactions of isobutyraldehyde. Activation energies for the stereogenic step have been determined by calculation of the transition state and substrate structures in dichloromethane solution at the B3LYP/6-311+G(2d,p)//B3LYP/6-31+G(d) level of theory in dichloromethane solution. The possibility to predict simple diastereoselectivity in general Lewis acid-mediated crotylations of aldehydes and ketones is discussed.