Direct coupling of unactivated alcohols remains a challenge in synthetic chemistry. Current approaches to cross-coupling of alcohol-derived electrophiles often involve activated alcohols such as tosylates or carbonates. We report the direct arylative substitution of homoallylic alcohols catalyzed by a nickel-bisphosphine complex as a facile method to generate allylic arenes. These reactions proceed via formation of an allylic alcohol intermediate. Subsequent allylic substitution with arylboroxine nucleophiles enables the formation of a variety of allylic arenes. The presence of p -methoxyphenylboronic acid is crucial to activate the allylic alcohol to achieve high product yields.
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Diastereoconvergent synthesis of anti -1,2-amino alcohols with N-containing quaternary stereocenters via selenium-catalyzed intermolecular C–H amination
We report a diastereoconvergent synthesis of anti -1,2-amino alcohols bearing N-containing quaternary stereocenters using an intermolecular direct C–H amination of homoallylic alcohol derivatives catalyzed by a phosphine selenide. Destruction of the allylic stereocenter during the selenium-catalyzed process allows selective formation of a single diastereomer of the product starting from any diastereomeric mixture of the starting homoallylic alcohol derivatives, eliminating the need for the often-challenging diastereoselective preparation of starting materials. Mechanistic studies show that the diastereoselectivity is controlled by a stereoelectronic effect (inside alkoxy effect) on the transition state of the final [2,3]-sigmatropic rearrangement, leading to the observed anti selectivity. The power of this protocol is further demonstrated on an extension to the synthesis of syn -1,4-amino alcohols from allylic alcohol derivatives, constituting a rare example of 1,4-stereoinduction.
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- Award ID(s):
- 2102267
- PAR ID:
- 10434047
- Date Published:
- Journal Name:
- Chemical Science
- Volume:
- 13
- Issue:
- 33
- ISSN:
- 2041-6520
- Page Range / eLocation ID:
- 9685 to 9692
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract We report herein the development of stereodivergent syntheses of enantioenriched homoallylic alcohols using chiral nonracemic α‐CH2Bpin‐substituted crotylboronate. Chiral phosphoric acid (
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Abstract We report herein the development of stereodivergent syntheses of enantioenriched homoallylic alcohols using chiral nonracemic α‐CH2Bpin‐substituted crotylboronate. Chiral phosphoric acid (
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A highly stereoselective synthesis of ( E )-δ-boryl- anti -homoallylic alcohols is developed. In the presence of a Lewis acid, aldehyde allylation with α-boryl-( E )-crotylboronate gave δ-boryl- anti -homoallylic alcohols in good yields with excellent E -selectivity. The E -vinylboronate group in the products provides a useful handle for cross-coupling reactions as illustrated in the fragment synthesis of chaxamycins.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d2sc02648a
