An official website of the United States government
Abstract We report herein a rare example of enantiodivergent aldehyde addition with β‐alkenyl allylic boronates via chiral Brønsted acid catalysis. 2,6‐Di‐9‐anthracenyl‐substituted chiral phosphoric acid‐catalyzed asymmetric allylation using β‐vinyl substituted allylic boronate gave alcohols withRabsolute configuration. The sense of asymmetric induction of the catalyst in these reactions is opposite to those in prior reports. Moreover, in the presence of the same acid catalyst, the reactions with β‐2‐propenyl substituted allylic boronate generated homoallylic alcohol products withSabsolute configuration. Unusual substrate‐catalyst C−H⋅⋅⋅π interactions in the favoured reaction transition state were identified as the origins of observed enantiodivergence through DFT computational studies.
more »
« less
Chiral Phosphoric Acid Dual‐Function Catalysis: Asymmetric Allylation with α‐Vinyl Allylboron Reagents
Abstract We report a dual function asymmetric catalysis by a chiral phosphoric acid catalyst that controls both enantioselective addition of an achiral α‐vinyl allylboronate to aldehydes and pseudo‐axial orientation of the α‐vinyl group in the transition state. The reaction produces dienyl homoallylic alcohols with highZ‐selectivities and enantioselectivities. Computational studies revealed that minimization of steric interactions between the alkyl groups of the diol on boron and the chiral phosphoric acid catalyst influence the orientation of α‐vinyl substituent of the allylboronate reagent to occupy a pseudo‐axial position in the transition state.
more »
« less
- Award ID(s):
- 1764328
- PAR ID:
- 10145837
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 59
- Issue:
- 26
- ISSN:
- 1433-7851
- Page Range / eLocation ID:
- p. 10540-10548
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
null (Ed.)A double divergent process has been developed for the reaction of α-enaminones with quinones through facile manipulation of catalyst and additive, leading to structurally completely different products. The two divergent processes, which involve formal aza- and oxo-[3 + 2] cycloaddition reactions, are mediated by chiral phosphoric acid and molecular sieves, respectively. While inclusion of phosphoric acid in the reaction switched the reaction pathway to favor the efficient formation of a wide range of N -substituted indoles, addition of 4 Å molecular sieves to the reaction switched the reaction pathway again, leading to enantioselective synthesis of 2,3-dihydrobenzofurans in excellent yields and enantioselectivities under mild conditions. Studies in this work suggest that the chiral phosphoric acid acts to lower the transition state energy and promote the formation of amide intermediate for the formal aza-[3 + 2] cycloaddition and the molecular sieves serve to facilitate proton transfer for oxo-[3 + 2] cycloaddition. The reactivity of α-enaminones is also disclosed in this work.more » « less
-
Abstract We report herein the development of stereodivergent syntheses of enantioenriched homoallylic alcohols using chiral nonracemic α‐CH2Bpin‐substituted crotylboronate. Chiral phosphoric acid (S)‐A‐catalyzed asymmetric allyl addition with the reagent gaveZ‐anti‐homoallylic alcohols with excellent enantioselectivities andZ‐selectivities. When the enantiomeric acid catalyst (R)‐Awas utilized, the stereoselectivity was completely reversed andE‐anti‐homoallylic alcohols were obtained with highE‐selectivities and excellent enantioselectivities. By pairing the chirality of the boron reagent with the catalyst, two complementary stereoisomers of chiral homoallylic alcohols can be obtained selectively from the same boron reagent. DFT computational studies were conducted to probe the origins of the observed stereoselectivity. These reactions generate highly enantioenriched homoallylic alcohol products that are valuable for rapid construction of polyketide structural frameworks.more » « less
-
Abstract Acyclic ketone‐derived oxocarbenium ions are involved as intermediates in numerous reactions that provide valuable products, however, they have thus far eluded efforts aimed at asymmetric catalysis. We report that a readily accessible chiral carboxylic acid catalyst exerts control over asymmetric cyclizations of acyclic ketone‐derived trisubstituted oxocarbenium ions, thereby providing access to highly enantioenriched dihydropyran products containing a tetrasubstituted stereogenic center. The high acidity of the carboxylic acid catalyst, which exceeds that of the well‐known chiral phosphoric acid catalyst TRIP, is largely derived from stabilization of the carboxylate conjugate base through intramolecular anion‐binding to a thiourea site.more » « less
-
Abstract Acyclic ketone‐derived oxocarbenium ions are involved as intermediates in numerous reactions that provide valuable products, however, they have thus far eluded efforts aimed at asymmetric catalysis. We report that a readily accessible chiral carboxylic acid catalyst exerts control over asymmetric cyclizations of acyclic ketone‐derived trisubstituted oxocarbenium ions, thereby providing access to highly enantioenriched dihydropyran products containing a tetrasubstituted stereogenic center. The high acidity of the carboxylic acid catalyst, which exceeds that of the well‐known chiral phosphoric acid catalyst TRIP, is largely derived from stabilization of the carboxylate conjugate base through intramolecular anion‐binding to a thiourea site.more » « less
