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. 2019 Feb 13;141(6):2251-2256.
doi: 10.1021/jacs.8b13907. Epub 2019 Feb 1.

Enantioselective Allylation Using Allene, a Petroleum Cracking Byproduct

Richard Y Liu  1 , Yujing Zhou  1 , Yang Yang  1 , Stephen L Buchwald  1
Affiliations

Enantioselective Allylation Using Allene, a Petroleum Cracking Byproduct

Richard Y Liu et al. J Am Chem Soc. .

Abstract

Allene (C3H4) gas is produced and separated on million-metric-ton scale per year during petroleum refining but is rarely employed in organic synthesis. Meanwhile, the addition of an allyl group (C3H5) to ketones is among the most common and prototypical reactions in synthetic chemistry. Herein, we report that the combination of allene gas with inexpensive and environmentally benign hydrosilanes, such as PMHS, can serve as a replacement for stoichiometric quantities of allylmetal reagents, which are required in most enantioselective ketone allylation reactions. This process is catalyzed by copper salts and commercially available ligands, operates without specialized equipment or pressurization, and tolerates a broad range of functional groups. Furthermore, the exceptional chemoselectivity of this catalyst system enables industrially relevant C3 hydrocarbon mixtures of allene with methylacetylene and propylene to be applied directly.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.. Overview of Allene-Based Ketone Allylation.
For experimental details, see the Supporting Information.
Figure 2.
Figure 2.. Extensions and applications of the allylation process.
Np = 2-naphthyl, for experimental details, see the Supplementary Information.
Figure 3.
Figure 3.. Model for the enantioselectivity of the ketone allylation process.
Energy values represent relative Gibbs free energies for transition states calculated using the M06/6–311+G(d,p)-SDD(Cu)/SMD(PhMe)//B3LYP/6–31G(d)-SDD(Cu).
See this image and copyright information in PMC

References

    1. Boström J; Brown DG; Young RJ; Keserü GM Expanding the Medicinal Chemistry Synthetic Toolbox. Nat. Rev. Drug Discov 2018, 17, 709–727. - PubMed
    2. Barker A; Kettle JG; Nowak T; Pease JE Expanding Medicinal Chemistry Space. Drug Discov. Today 2013, 18, 298–304. - PubMed
    1. Gaich T; Baran PS Aiming For The Ideal Synthesis. J. Org. Chem 2010, 75, 4657–4673. - PubMed
    2. Anastas PT; Warner JC Green Chemistry: Theory and Practice; Oxford University Press: Oxford, U.K., 1998.
    1. Smith KT; Berritt S; González-Moreiras M; Ahn S; Smith MR III; Baik M-H; Mindiola DJ Catalytic Borylation Of Methane. Science 2016, 351, 1424–1427. - PMC - PubMed
    1. Hu A; Guo J-J; Pan H; Zuo Z Selective Functionalization of Methane, Ethane, and Higher Alkanes by Cerium Photocatalysis. Science 2018, 361, 668–672. - PubMed
    1. Mo F; Dong. G. Regioselective Ketone α-Alkylation with Simple Olefins via Dual Activation. Science 2014, 345, 68–72. - PubMed

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