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.

Dendralenes Branch Out: Cross‐Conjugated Oligoenes Allow the Rapid Generation of Molecular Complexity

“…It was also demonstrated for the first time that enantioselective Diels-Alder reactions with the parent [3]dendralene (11) are possible. Thus, through the application of a modified [28,202] version of Coreys oxazaborolidinium catalyst, 243, the mono-cycloaddition of methyl acrylate to [3]dendralene (11) produced monoadduct 239 in a respectable 86 % yield and 92 % ee. It was demonstrated that the presence of a bicyclic framework is not necessary for good anti-p-diastereofacial stereoselectivity (cf.…”

Chiral 1,3,2-Oxazaborolidine Catalysts for Enantioselective Photochemical Reactions

“…However, there are instances in which a different transition state structure is favored because of other steric or electronic interactions. 44 Therefore, detailed analysis for each individual reaction and substrate seems to be necessary. The role of aluminum bromide in the thermal catalysis of 1,3,2-oxazaborolidines was investigated through computational studies by Sakata and Fujimoto.…”

Dendralene auf dem Vormarsch: kreuzkonjugierte Oligoene ermöglichen den schnellen Aufbau molekularer Komplexität

“…In diesen Untersuchungen wurde zudem erstmals gezeigt, dass mit dem Stammkohlenwasserstoff 11 auch enantioselektive Diels-Alder-Additionen mçglich sind. Beispielsweise ließ sich durch Nutzung einer modifizierten Form [28,202] [53,54,156] Erst 1992 identifizierten Trahanovsky und Koeplinger als Hauptprodukt der thermischen Dimerisierung das Diels-Alder-Produkt 242. [156] Daten zur Geschwindigkeit der Dimerisierung von 11 als reiner Flüssigkeit bei Raumtemperatur wurden gar erst 2010 ermittelt.…”