Palladium‐Catalyzed Defluorinative Coupling of 1‐Aryl‐2,2‐Difluoroalkenes and Boronic Acids: Stereoselective Synthesis of Monofluorostilbenes

Abstract

The palladium-catalyzed defluorinative coupling of 1-aryl-2,2-difluoroalkenes with boronic acids is described. Broad functional group tolerance arises from a redox-neutral process via a Pd(II) active species that is proposed to undergo a β-fluoride elimination to afford the products. The monofluorostilbene products were formed with excellent diastereoselectivity (≥50:1) in all cases, which is critical, as traditional chromatographic techniques often fail to separate monofluoroalkene isomers. As a demonstration of this method’s unique combination of reactivity and functional group tolerance, a Gleevec© analogue using a monofluorostilbene as an amide isostere was synthesized.

Rapid access to diverse, trifluoromethyl-substituted alkenes using complementary strategies

“…The latter emphasizes the utility of these α-trifluoromethyl-β-silyl alcohols as masked trifluoromethyl alkenes, given the propensity of trifluoromethyl alkenes to undergo defluorinative amination under basic conditions. 16 …”

Transition‐Metal‐Mediated and ‐Catalyzed C−F Bond Activation by Fluorine Elimination

“…Thornbury and Toste then succeeded in the catalytic defluorinative arylation of b,b-difluorostyrenes with arylboronic acids by using palladium(II) trifluoroacetate as acatalyst and 4,4'-di-tert-butyl-2,2'-bipyridine (dtbpy) as al igand (Scheme 14 b). [31] Cao and co-workers reported the synthesis of furans by the Cu I -catalyzed domino CÀFbond activation of b,b-difluorostyrenes by using active methylene carbonyl compounds (not shown). [32] Hoveyda and co-workers demonstrated the copper-catalyzed allylic CÀFb ond borylation of a-(trifluoromethyl)styrene with B 2 (pin) 2 by insertion into borylcopper(I) species and b-fluorine elimination (Scheme 15 a).…”

Stereoselective Synthesis of Z-Fluorostyrene Derivatives via Nickel-Catalyzed Cross-Coupling of gem-Difluorostyrenes with Organozinc Reagents

“…值得补充说明的是, 最近有关偕二氟烯烃在过渡金 属催化下与有机金属试剂的偶联反应的机理有两种代 表性的反应途径. 一种反应途径是由 Ogoshi 等 [16,22] 提出 的烯烃碳氟键发生的氧化加成机理; 另一种途径是由 Toste 和 Ichikawa 等 [23] 推测的加成消除机理. 但根据我 有机化学 研究论文 表 2 偕二氟芳基乙烯与有机锌反应的底物范围考察 a Table 2 Scope and limitations of the reaction…”