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