No 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.

High cis (i.e., endo) diastereoselectivities are witnessed in heat-promoted intramolecular Diels-Alder (IMDA) reactions of ethylene-tethered hexadienyl acrylates. The cis stereoselectivity is improved by promotion with Et2AlCl. The first examples of Et2AlCl catalyzed intramolecular Diels-Alder reactions of ester-activated dienophiles are reported. In contrast, the corresponding benzo-tethered hexadienyl acrylates undergo moderately trans (i.e., exo) selective IMDA reactions. Very high trans stereoselection is obtained upon promotion with ATPH. The outcomes of these reactions are essentially insensitive to dienophile (C10) geometry and substitution. DFT (B3LYP/6-31+G(d)) computed cis/trans product distributions-based on Boltzmann transition structure populations-are in good agreement with the experimental results. These computational investigations provide useful insights into the origins of stereoselection in these systems. The stereoselectivity exhibited by the ethylene-tethered hexadienyl acrylates is ascribed to stabilizing secondary orbital interactions at play in the cis-transition structures (TSs). In the benzo-tethered series, this effect is overridden by stabilizing pi-conjugative interactions, between the benzo moiety and the 1,3-diene component, which are stronger in trans TSs, compared to the cis TSs. The computed TS geometries generally exhibit advanced peripheral bond forming asynchronicity, with the tether carbonyl group in conjugation with the dienophile. Such TS features significantly weaken the stereodirecting influence of terminal dienophile substituents.

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.