Enantioselective Oxazaborolidinium‐Catalyzed Diels–Alder Reactions without CH⋅⋅⋅⋅O Hydrogen Bonding

Abstract

The oxazaborolidine Diels-Alder (DA) precatalysts first introduced by Corey et al. in 2002 [1] are remarkable for several reasons. The derived oxazaborolidinium cations, for example 1 a·HNTf 2 or 1 a·MX n (formed by exposure to either Brønsted [1][2][3] or Lewis [4] acids, Scheme 1), are active catalysts for enantioselective cycloadditions involving a broad range of dienes and dienophiles. [1][2][3][4][5][6][7][8][9][10][11][12] Perhaps the most significant quality of this family of Lewis acid (LA) catalysts, however, lies in their singular ability to promote cycloadditions of dienophiles carrying simple, common functional groups. Interestingly, aldehyde-activated dienophiles give the opposite p-enantiofacial selectivity relative to that of the corresponding esters, carboxylic acids, and ketones in reactions promoted by 1 a. This observation was explained by Corey and co-workers [2] in terms of the pre-transition-state assemblies shown in Scheme 1. A pivotal feature of these pretransition-state models is the presence of an O···HC hydrogen bond, which is believed to facilitate p-enantiofacial selectivity by constraining the orientation of the dienophile-LA complex. Herein we present computational and experimental evidence that certain enantioselective DA reactions may take place in the absence of O···HC hydrogen bonding and that they might even prefer this pathway over the normal Corey pathway.Certain intermolecular, intramolecular, and transannular DA reactions of ester-activated dienophiles catalyzed by oxazaborolidinium species furnish products which do not correlate with the Corey pre-transition-state model shown in Scheme 1. Thus, under oxazaborolidinium catalysis, [13] a-methylene-g-butyrolactone (2) undergoes a highly exoselective intermolecular DA reaction with cyclopentadiene to give adduct 3 (Scheme 2 a) as the major stereoisomer, and triene 4 undergoes a highly cis-selective intramolecular DA reaction to give 5 (Scheme 2 b). In a series of elegant Scheme 1. Corey's oxazaborolidinium catalyst and pre-transition-state models (i.e. diene absent). a) Proposed mode of complexation for aldehydes. b) Proposed mode of complexation for ketones, esters, and acids.Scheme 2. DA reactions proceeding with enantioselectivities that vary relative to those predicted by the Corey O···HC hydrogen-bonding model. a) and b) are results from this work, and c) is a result from the work of Balskus and Jacobsen.

Bifunctional Acid Catalysts for Organic Synthesis

“…In this case, dienophiles lacking the typical hydrogen bond donor moiety required by Corey's pretransition state assembly model can also give rise to high enantioselectivities. These results echoed the previous study by Paddon-Row and co-workers on related cationic oxazaborolidine catalyzed Diels-Alder reaction without involvement of hydrogen bonding, in which other stereoelectronic effects may contribute to the preorganization of Lewis acid/carbonyl coordination [49]. Considering the Fig.…”

Quantum Mechanical Investigations of Organocatalysis: Mechanisms, Reactivities, and Selectivities

“…247 Key features of Corey‘s models include: (1) a preferred s-trans C=C-C=O conformation of the dienophile, (2) πstacking between the dienophile and the exo- phenyl group at C-5 of the catalyst, and (3) catalyst binding to the oxygen anti lone pair (with respect to the double bond) and formyl hydrogen in the case of aldehydes, versus catalyst binding to the syn oxygen lone pair and α-hydrogen of ketones, esters, and carboxylic acids. These different binding modes expose opposite faces of the dienophile and explain the opposite enantioselectivities observed experimentally.…”

Computational Evaluation of Enantioselective Diels−Alder Reactions Mediated by Corey’s Cationic Oxazaborolidine Catalysts

“…Recently, Paddon-Row et al reported a computational study of oxazaborolidinium-catalyzed intramolecular DA reactions which showed, among other things, that the Curtin-Hammett approximation holds in such catalyzed IMDA reactions and that predicted enantioselectivities, derived solely from differences in the transition structure free energies; the results were in good accord with the experimental enantioselectivities xi. This computational study extends the scope of that earlier work by investigating, using density functional theory (B3LYP/6-31G(d)), oxazaborolidinium-catalyzed intermolecular DA reactions of 1,3-butadiene with several different dienophiles, namely methacrolein ( 1 ), acrolein ( 12 ), methyl acrylate ( 13 ), dimethyl fumarate ( 14 ) and 2-methylbenzoquinone ( 15 ) (Figure 3).…”