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. 2022 Aug 31;144(34):15480-15487.
doi: 10.1021/jacs.2c07297. Epub 2022 Aug 17.

Enantioselective and Diastereodivergent Allylation of Propargylic C-H Bonds

Jin Zhu  1 , Yidong Wang  1   2 , Aaron D Charlack  1 , Yi-Ming Wang  1
Affiliations

Enantioselective and Diastereodivergent Allylation of Propargylic C-H Bonds

Jin Zhu et al. J Am Chem Soc. .

Abstract

An iridium-catalyzed stereoselective coupling of allylic ethers and alkynes to generate 3,4-substituted 1,5-enynes is reported. Under optimized conditions, the coupling products are formed with excellent regio-, diastereo-, and enantioselectivities, and the protocol is functional group tolerant. Moreover, we report conditions that allow the reaction to proceed with complete reversal of diastereoselectivity. Mechanistic studies are consistent with an unprecedented dual role for the iridium catalyst, enabling the propargylic deprotonation of the alkyne through π-coordination, as well as the generation of a π-allyl species from the allylic ether starting material.

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Figures

Scheme 1.
Scheme 1.
Asymmetric propargylic functionalization for 1,5-enyne synthesis
Scheme 2.
Scheme 2.
Preliminary results for propargylic C–H allylation
Scheme 3.
Scheme 3.. Diversification of product 3na
aConditions: (a) Ph3PAuCl (cat.), AgSbF6 (cat.), CH2Cl2, rt, 0.5 h; (b) Sulfonamide 8S, Pd(OAc)2 (cat.), Ph3P (cat.), Cs2CO3, CsI, norbornene, DMF, 130 °C, 12 h; (c) 9-BBN, THF, 2h; NaBO3·H2O, H2O, rt, 3 h; (d) TsCl, Et3N, DMAP, CH2Cl2, rt, 4 h; (e) BnNH2, K2CO3, MeCN, reflux, 22 h.
Scheme 4.
Scheme 4.
Selected mechanistic studies and proposed catalytic cycle
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