Post on 20-Jan-2021
Hydrocarbon Surrogates for Organometallic Reagents:
CuH-Catalyzed Stereoselective Addition from OlefinsRichard Y. Liu, Yujing Zhou, Chengxi Li, Kwangmin Shin, Yang Yang,
Erica Y. Tsai, and Stephen L. BuchwaldDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, United States
Ketone Addition Reactions Using Allene (C3H4)
Allene: an Unexploited Feedstock
Allene-Based Allylation: Extending the Scope
Selected Applications
Industrially Relevant Gas Mixtures
Efficient Synthesis of an Anti-Psychotic Thioxanthene Drug
Reactions of Substituted Allenes
Stereochemical ModelThis research was supported by the
National Institutes of Health under grants
GM58160 and GM122483 and through a
supplemental grant for a supercritical
fluid chromatography (SFC) instrument.
Y.Z. and R.Y.L. thank Bristol-Myers
Squibb for support through fellowships.
E.Y.T. thanks the National Science
Foundation for financial support. We
thank Nippon Chemical Industrial Co.,
Ltd., Solvias AG, Takasago Intl.
Corporation, and MilliporeSigma for
donations of ligands.
References:
Allene Gas: Liu, R. Y.*; Zhou, Y.*; Yang,
Y.; Buchwald, S. L. J. Am. Chem. Soc.
2019, 141, 2251.
Substituted Allenes: Tsai, E. Y.; Liu, R.
Y.; Yang, Y.; Buchwald, S. L. J. Am.
Chem. Soc. 2018, 140, 2007.
Imines: Liu, R. Y.; Yang, Y.; Buchwald, S.
L. Angew. Chem. Int. Ed. 2016, 55,
14077.
Dienes + Ketones: Li, C.; Liu, R. Y.;
Jesikiewicz, L. T.; Yang. Y.; Liu, P.;
Buchwald, S. L. J. Am. Chem. Soc. 2019,
141, 5062.
Dienes + Aldehydes: Li, C.; Shin, K.;
Liu, R. Y.; Buchwald, S. L. Angew. Chem.
Int. Ed. 2019, 131, 17230.
Short Review: Liu, R. Y.; Buchwald, S.
L. Acc. Chem. Res. 2020, 53, 1229.
Regiodivergent Addition to Iminescoordination to O
promotes internal bond
formation
coordination to N
promotes distal bond
formation
Design and Optimization
1,3-Dienes as Pronucleophiles
Ketone Allylation
Examples
Organometallic Addition to Carbonyl Compounds
Aldehyde Allylation
Traditional, Two-Step Approach Our One-Step Approach
n highly basic conditions, low tolerance for complex substrates
n must control regio- and stereoselectivity for both steps
n expensive or unstable intermediates
n chiral controllers or specialized ligands required
n stoichiometric metal waste
n may generate insoluble salts
n neutral conditions
n catalyst-controlled regio- and stereoselectivity
n no isolation of intermediates
n Earth-abundant metal, commercially available ligands
n cheap and environmentally benign silane reagent
n fully homogeneous
Precursor Organometallic Adduct Catalytic
Intermediate
(not isolated)
Olefin