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Abstract Alkenes are a central part of organic chemistry1–3. However, although most alkenes are easy to prepare, the controlled synthesis of tetrasubstituted alkenes, those with four groups around the central C=C bond, remains challenging1–5. Here we report the boron-mediated assembly of tetrasubstituted alkenes with complete control of the double-bond geometry. The migrating group and electrophile add syn across the alkyne. Mild oxidation leads to intermediate borinic esters6, which can be isolated and purified or reacted directly in a range of transformations, including cross-couplings and homologation reactions. In particular, subjecting the intermediate borinic esters to Zweifel7,8olefination conditions can give either retention or inversion of the double-bond geometry, depending on whether base is present or not. Different positional and stereoisomers of the tetrasubstituted alkenes can be easily accessed, highlighting the breadth and versatility of the method. This was showcased through its successful application to the rapid synthesis of drug molecules and natural products with high yield and stereocontrol. Not only does this method provide efficient access to the long-standing challenge of the stereocontrolled synthesis of tetrasubstituted alkenes but it also introduces new concepts related to the intervention of non-classical borenium ions in the Zweifel olefination.
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Asymmetric Reductive Dicarbofunctionalization of Alkenes via Nickel Catalysis
Alkenes are an appealing functional group that can be transformed into a variety of structures. Transition-metal catalyzed dicarbofunctionalization of alkenes can efficiently afford products with complex substitution patterns from simple substrates. Under reductive conditions, this transformation can be achieved while avoiding stoichiometric organometallic reagents. Asymmetric difunctionalization of alkenes has been underdeveloped, in spite of its potential synthetic utility. Herein, we present a summary of our efforts to control enantioselectivity for alkene diarylation with a nickel catalyst. This reaction is useful for preparing triarylethanes. The selectivity is enhanced by an N-oxyl radical additive.
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- Award ID(s):
- 1654483
- PAR ID:
- 10208012
- Date Published:
- Journal Name:
- Synlett
- Volume:
- 31
- Issue:
- 15
- ISSN:
- 0936-5214
- Page Range / eLocation ID:
- 1443 to 1447
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract: A colorimetric indicator displacement assay (IDA) amenable to high-throughput experimentation was developed to determine the percentage of cis and trans alkenes. Using 96-well plates two steps are performed: a reaction plate for dihydroxylation of the alkenes followed by an IDA screening plate consisting of an indicator and a boronic acid. The dihydroxylation generates either erythro or threo vicinal diols from cis or trans alkenes, depending upon their syn- or antiaddition mechanisms. Threo diols preferentially associate with the boronic acid due to the creation of more stable boronate esters, thus displacing the indicator to a greater extent. The generality of the protocol was demonstrated using seven sets of cis and trans alkenes. Blind mixtures of cis and trans alkenes were made, resulting in an average error of 2% in the percentage of cis or trans alkenes, and implementing E2 and Wittig reactions gave errors of 3%. Furthermore, we developed variants of the IDA for which the color may be tuned to optimize the response for the human eye.more » « less
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Abstract Because internal alkenes are more challenging synthetic targets than terminal alkenes, metal‐catalyzed olefin mono‐transposition (i.e., positional isomerization) approaches have emerged to afford valuableE‐ orZ‐internal alkenes from their complementary terminal alkene feedstocks. However, the applicability of these methods has been hampered by lack of generality, commercial availability of precatalysts, and scalability. Here, we report a nickel‐catalyzed platform for the stereodivergentE/Z‐selective synthesis of internal alkenes at room temperature. Commercial reagents enable this one‐carbon transposition of terminal alkenes to valuableE‐ orZ‐internal alkenes via a Ni−H‐mediated insertion/elimination mechanism. Though the mechanistic regime is the same in both systems, the underlying pathways that lead to each of the active catalysts are distinct, with theZ‐selective catalyst forming from comproportionation of an oxidative addition complex followed by oxidative addition with substrate and theE‐selective catalyst forming from protonation of the metal by the trialkylphosphonium salt additive. In each case, ligand sterics and denticity control stereochemistry and prevent over‐isomerization.more » « less
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1055/s-0040-1707900
