Chiral Brønsted Acid-Catalyzed Asymmetric Allyl(propargyl)boration Reaction of ortho-Alkynyl Benzaldehydes: Synthetic Applications and Factors Governing the Enantioselectivity

Elsa Rodríguez; Matthew N. Grayson; Amparo Asensio; Pablo Barrio; K. N. Houk; Santos Fustero

doi:10.1021/acscatal.6b00209

Chiral Brønsted Acid-Catalyzed Asymmetric Allyl(propargyl)boration Reaction of ortho-Alkynyl Benzaldehydes: Synthetic Applications and Factors Governing the Enantioselectivity

Elsa Rodríguez, Matthew N. Grayson, Amparo Asensio, Pablo Barrio, K. N. Houk, Santos Fustero

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

46 Citations (SciVal)

Abstract

Chiral Brønsted acid-catalyzed allyl(propargyl)boration of ortho-alkynyl benzaldehydes gives rise to ω-alkynyl homoallylic(homopropargylic)alcohols that can be further transformed to complex molecular scaffolds via subsequent hydroalkoxylation, ring-closing enyne metathesis (RCEYM), or intramolecular Pauson-Khand reaction (PKR). Optimizations of each two-step transformation is reported. A strong dependence between enantioselectivities and the nature of the substitution at the alkynyl moiety is observed, showcasing that the triple bond is not merely a spectator in this transformation. Density functional theory (DFT) calculations (M06-2X/6-311+G(d,p)-IEFPCM//B3LYP/6-31G(d)) show that this dependence is the result of the steric and electronic properties of the alkyne substituent.

Original language	English
Pages (from-to)	2506-2514
Number of pages	9
Journal	ACS Catalysis
Volume	6
Issue number	4
Early online date	7 Mar 2016
DOIs	https://doi.org/10.1021/acscatal.6b00209
Publication status	Published - 1 Apr 2016

Funding

We would like to thank the Spanish MINECO (CTQ2013-43310) and the Generalitat Valenciana (PROMETEOII/2014/073) for their financial support. E.R. expresses her thanks to Universidad de Valencia for a predoctoral fellowship. A.A. is grateful to the Ministerio de Educacion, Cultura y Deportes for a grant (PRX12/00347). Technical and human support provided by SGIker (UPV/EHU, MINECO, GV/EJ, ERDF, and ESF) is gratefully acknowledged. We are grateful to The English-Speaking Union (Lindemann Trust Fellowship to M.N.G.) and the NSF (CHE-1361104 to K.N.H.) for financial support. Computational resources were provided by the UCLA Institute for Digital Research and Education (IDRE) and the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by the NSF (OCI-1053575).

Keywords

asymmetric allylboration
chiral Brønsted acids
DFT calculations
diversity-oriented synthesis
organocatalysis

ASJC Scopus subject areas

Catalysis

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10.1021/acscatal.6b00209

Cite this

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title = "Chiral Br{\o}nsted Acid-Catalyzed Asymmetric Allyl(propargyl)boration Reaction of ortho-Alkynyl Benzaldehydes: Synthetic Applications and Factors Governing the Enantioselectivity",

abstract = "Chiral Br{\o}nsted acid-catalyzed allyl(propargyl)boration of ortho-alkynyl benzaldehydes gives rise to ω-alkynyl homoallylic(homopropargylic)alcohols that can be further transformed to complex molecular scaffolds via subsequent hydroalkoxylation, ring-closing enyne metathesis (RCEYM), or intramolecular Pauson-Khand reaction (PKR). Optimizations of each two-step transformation is reported. A strong dependence between enantioselectivities and the nature of the substitution at the alkynyl moiety is observed, showcasing that the triple bond is not merely a spectator in this transformation. Density functional theory (DFT) calculations (M06-2X/6-311+G(d,p)-IEFPCM//B3LYP/6-31G(d)) show that this dependence is the result of the steric and electronic properties of the alkyne substituent.",

keywords = "asymmetric allylboration, chiral Br{\o}nsted acids, DFT calculations, diversity-oriented synthesis, organocatalysis",

author = "Elsa Rodr{\'i}guez and Grayson, {Matthew N.} and Amparo Asensio and Pablo Barrio and Houk, {K. N.} and Santos Fustero",

year = "2016",

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doi = "10.1021/acscatal.6b00209",

language = "English",

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AU - Rodríguez, Elsa

AU - Grayson, Matthew N.

AU - Asensio, Amparo

AU - Barrio, Pablo

AU - Houk, K. N.

AU - Fustero, Santos

PY - 2016/4/1

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N2 - Chiral Brønsted acid-catalyzed allyl(propargyl)boration of ortho-alkynyl benzaldehydes gives rise to ω-alkynyl homoallylic(homopropargylic)alcohols that can be further transformed to complex molecular scaffolds via subsequent hydroalkoxylation, ring-closing enyne metathesis (RCEYM), or intramolecular Pauson-Khand reaction (PKR). Optimizations of each two-step transformation is reported. A strong dependence between enantioselectivities and the nature of the substitution at the alkynyl moiety is observed, showcasing that the triple bond is not merely a spectator in this transformation. Density functional theory (DFT) calculations (M06-2X/6-311+G(d,p)-IEFPCM//B3LYP/6-31G(d)) show that this dependence is the result of the steric and electronic properties of the alkyne substituent.

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Chiral Brønsted Acid-Catalyzed Asymmetric Allyl(propargyl)boration Reaction of ortho-Alkynyl Benzaldehydes: Synthetic Applications and Factors Governing the Enantioselectivity

Abstract

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ASJC Scopus subject areas

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Matt Grayson

High Performance Computing (HPC) Facility

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Chiral Brønsted Acid-Catalyzed Asymmetric Allyl(propargyl)boration Reaction of ortho-Alkynyl Benzaldehydes: Synthetic Applications and Factors Governing the Enantioselectivity

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Profiles

Matt Grayson

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High Performance Computing (HPC) Facility

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