Synlett 2013; 24(5): 611-614
DOI: 10.1055/s-0032-1318313
letter
© Georg Thieme Verlag Stuttgart · New York

Pd-Catalyzed Allylic Alkylation of CF3-Containing Esters with Three Electron-Withdrawing Groups

Lun Li
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China   Fax: +86(21)64166128   Email: yguo@sioc.ac.cn
,
Donghui Huang
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China   Fax: +86(21)64166128   Email: yguo@sioc.ac.cn
,
Qing-Yun Chen
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China   Fax: +86(21)64166128   Email: yguo@sioc.ac.cn
,
Yong Guo*
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China   Fax: +86(21)64166128   Email: yguo@sioc.ac.cn
› Author Affiliations
Further Information

Publication History

Received: 09 January 2013

Accepted after revision: 04 February 2013

Publication Date:
20 February 2013 (online)


Abstract

Tsuji–Trost reaction (Pd-catalyzed allylic alkylation) of CF3-containing esters with three electron-withdrawing groups is reported. The reactions with methyl bis(trifluoromethyl)acetate and dimethyl (trifluoromethyl)malonate were carried out with low-loading catalysts of Pd(0) and XPhos at ambient temperature in THF, giving the products in high yields. This method efficiently overcomes the β-defluorination, which is hard to control in the chemical transformation of α-trifluoromethyl carbanions, and provides versatile fluorinated compounds with quaternary carbon centers, which are highly demanded in drug discovery.

Supporting Information

Primary Data

 
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  • 10 Typical Procedure for the Preparation of Compound 4 To a solution of Pd(dba)2 (0.04 mmol) and XPhos (0.1 mmol) in THF (2 mL) were added at r.t. under N2 atmosphere, and the mixture was stirred for 30 min at r.t., then carbonate (0.4 mmol) was added dropwise under N2 atmosphere. After 10 min, CF3-containing ester 1 or 2 was added to the mixture dropwise, and the mixture was allowed to react at r.t. for 12 h. Then the solvent was evaporated under vacuum. The residue was purified by column chromatography on silica gel eluting using a mixture of hexane and CH2Cl2 as eluent. (E)-Methyl 5-Phenyl-2,2-bis(trifluoromethyl)pent-4-enoate (4a) 1H NMR (300 MHz, CDCl3): δ = 7.35–7.24 (m, 5 H), 6.58 (d, J = 15.9 Hz, 1 H), 6.06 (dt, J = 15.9, 7.2 Hz, 1 H), 3.89 (s, 3 H), 3.08 (d, J = 7.2 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ = 162.6, 136.5, 135.9, 128.6, 127.9, 126.5, 122.5 (q, J CF = 284 Hz), 120.2, 61.5 (m, J CF = 25 Hz), 53.9, 32.1. 19F NMR (282 MHz, CDCl3): δ = –66.5 (s). IR (neat): 282 3085, 3028, 2961, 1760, 1600, 1496, 1297, 1147, 1025 cm–1. MS (EI): m/z (%) = 326 (13.71) [M+]. HRMS (EI): m/z calcd for C14H12O2F6 [M+]: 326.0741; found: 326.0743.