Catalytic and Asymmetric Process via P^III/P^V═O Redox Cycling: Access to (Trifluoromethyl)cyclobutenes via a Michael Addition/Wittig Olefination Reaction

Abstract

In the present study, we report the first enantioselective and highly efficient phosphine-catalyzed process via a chemoselective in situ phosphine oxide reduction. Starting with 4,4,4-trifluorobutane-1,3-dione and dialkyl acetylenedicarboxylate substrates, highly functionalized fluorinated cyclobutenes were obtained in excellent yields and enantioselectivities. Using the same methodology, CF3-spirocyclobutene derivatives were also synthesized (34 examples, up to 95% ee).

Convergent Synthesis of Polysubstituted Furans via Catalytic Phosphine Mediated Multicomponent Reactions

“…nBu 3 P=O (20 mol%) instead of nBu 3 P; 51% yield nBu 3 P=O (100 mol%) instead of nBu 3 P; 58% yield without nBu Control experiments.Based on the results of this work and previous reports[59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75]97], a multiple domino process is proposed to rationalize the formation of tetra-substituted furans 3 (Scheme 5, left). The catalytic cycle starts with the nucleophilic addition of nBu3P to an activate alkene 1 like acrylates, the resulting intermediate undergoes a C-acylation reaction with acyl chloride 2 to give a phosphonium enolate A.…”

“…Under the reported conditions, various reducible functional groups such as ketones, aldehydes, olefins, nitriles, and esters were well tolerated. Based on these encouraging findings, a number of important stoichiometric phosphine-involved reactions, including (aza-)Wittig [59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75], Mitsunobu [76][77][78], Staudinger [79][80][81][82][83][84], Appel [85,86], Cadogan [87], and others [88][89][90][91][92][93] have been successfully developed into the catalytic phosphine mediated ones.…”

Advances in the catalytic asymmetric synthesis of quaternary carbon containing cyclobutanes

“…In 2019, the Voituriez group developed the first catalytic asymmetric Michael addition/Wittig reaction to synthesize highly functionalized CF 3 -substituted spirocyclobutene 167 bearing two contiguous stereogenic centers (Scheme 47). 54 This process started from the reduction of the phosphine oxide catalyst 168 to afford chiral phosphine I, which could then add to dialkyl acetylene dicarboxylate 98 to form the zwitterionic species II. Intermolecular proton transfer that occurred between II and CF 3 -dihydro-1H-indenone 166 and the subsequent addition reaction could form in situ ylide intermediate III.…”

Phosphine‐Catalyzed Synthesis of Chiral N‐Heterocycles through (Asymmetric) P(III)/P(V) Redox Cycling

“…The same year, we developed the first catalytic and asymmetric tandem Michael addition/Wittig reaction. [12] Excellent yields and up to 95 % ee have been obtained for the synthesis of fluorinated cyclobutene and spiro[3.4]octanone derivatives (Scheme 1c). In recent years, we also developed a straightforward phosphinecatalyzed methodology for the synthesis of many nitrogencontaining heterocycles, including 2,3-dihydro-1,3,4-oxadiazole, 9H-pyrrolo[1,2-a]indoles, pyrrolizines, 1,2-dihydroquinolines and others, with preliminary results in asymmetric catalysis.…”

“…First, we screened HypPhos phosphines P1-P9, which have previously demonstrated their effectiveness in phosphine organocatalysis. [11,12,16] If as a general trend, the isolated yields were moderate (up to 55 % yield in 3 e with the use of P2), the enantioselectivity reached 82 % ee with chiral phosphine exo-1naphthyl-P9. This catalytic reaction condition was also used Table 1.…”