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Author Contributions
†These authors contributed equally.
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
The authors are grateful to Nippon Chemical Industrial Co.,
Ltd., to Solvias AG, to Takasago International Corporation, and
to MilliporeSigma for donations of ligands used in this project.
Research reported in this publication was supported by the
National Institutes of Health under grants GM58160 and
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GM122483. The authors further thank the NIH for
a
supplemental grant for a supercritical fluid chromatography
instrument (SFC) under grant GM58160-17S1. This content is
solely the responsibility of the listed authors and does not
claim to represent the official views of the NIH. Y.Z. and R.Y.L.
thank Bristol-Myers Squibb for support through fellowships.
We acknowledge Christine Nguyen, Joseph Dennis, and Scott
McCann for advice on the preparation of this manuscript.
11. According to comprehensive chemical databases (see the
Supporting Information for details), the allyl group is the most
common three-carbon nucleophile, typically introduced using
stoichiometric organomagnesium (Grignard) reagents (see ref.
12). Moreover, among all reactions employing allylic Grignard
reagents, the majority involve specifically the parent allyl, rather
than substituted allyl groups, and the majority of electrophilic
partners are carbonyl derivatives such as ketones. For an
overview of stereoselective allylation, see: Corey, E. J.; Kurti, L.
Enantioselective Chemical Synthesis: Methods, Logic and
Practice; Direct Book Publishing: Dallas, 2010.
12. (a) Grignard, V. Sur Quelques Nouvelles Combinaisons
Organométaliques du Magnesium et Leur Applications à des
Syntheses d’Alcools et d’Hydrocarbures. Compt. Rend. 1900, 130,
1322–1325. (b) Read, J. A.; Woerpel, K. A. Allylmagnesium
Halides Do Not React Chemoselectively because Reaction Rates
Approach the Diffusion Limit. J. Org. Chem. 2017, 82, 2300–2305.
(c) Bartolo, N. D.; Woerpel, K. A. Mechanistic Insight into
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Org. Chem. 2018, 83, 10197–10206.
13. Cervera-Padrell, A. E.; Nielsen, J. P.; Pedersen, M. J.; Christensen,
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14. For examples of ketone allylation using stoichiometric quantities
of chiral allylmetal reagents, see: (a) Burns, N. Z.; Hackman, B.
M.; Ng, P. Y.; Powelson, I. A.; Leighton, J. L. The Enantioselective
Allylation and Crotylation Of Sterically Hindered and
Functionalized Aryl Ketones: Convenient Access to Unusual
Tertiary Carbinol Structures. Angew. Chem. Int. Ed. 2006, 45,
3811–3813. (b) Canales, E.; Prasad, K. G.; Soderquist, J. A. B-Allyl-
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