Iridium-Catalyzed Enantioselective Allyl–Alkene Coupling

Abstract

The direct Ir-catalyzed cross-coupling between branched, racemic allylic alcohols and simple olefins is described. This transformation is catalyzed by an Ir-(P,olefin) complex and proceeds with high site selectivity and excellent enantioselectivity. The method allows rapid access to various 1,5-dienes or trienes and was used in the catalytic asymmetric synthesis of the γ-secretase modulator JNJ-40418677.

Iridium‐Catalyzed Asymmetric Allylic Aromatization Reaction

“…[7e, 11] Gratifyingly,when Yb(OTf) 3 , In(OTf) 3 ,a nd Fe(OTf) 2 were tested, the reactions worked better,a ffording 3a in 58-70 %y ields.N ext, as eries of solvents were evaluated with Fe(OTf) 2 as the promoter, and DCE was identified as the optimal choice (entries [6][7][8][9]. With an Ir complex derived from [Ir(cod)Cl] 2 (3 mol %) and the Carreira (P,o lefin) ligand (S)-L1 (12 mol %) as the catalyst, and diphenylsulfonimide as the promoter for the electrophile,the reaction proceeded in 1,2-dichloroethane (DCE) and afforded the desired product 3a in 30 %yield (entry 1).…”

4-Trifluoromethyl-p-quinols as dielectrophiles: three-component, double nucleophilic addition/aromatization reactions

“…In the present research, the three-component reactions of 4-(trifluoromethyl)- p -quinol silyl ether 1a as double electrophile32, 1-dodecanethiol as S-nucleophile ( Nu1 )25262740 and acetone 2a as C-nucleophile ( Nu2 ) were first examined (Fig. 3).…”

“…Trifluoromethyl containing motifs in an aromatic system are common pharmacophores (Fig. 1)1224252627282930 and there is a great current interest in the discovery of trifluoromethylation methods upon electrophilic and radical trifluoromethylations of arenes and heteroarenes as a consequence of advances in catalysis3456789, and new trifluoromethylating reagents and methods678910111213. Such growth based on the late-stage introduction of a trifluoromethyl group onto a aryl ring is in stark contrast to the synthetic applications of trifluoromethyltrimethylsilane (TMSCF 3 , also known as Ruppert−Prakash reagent)1415, as notably less toxic, relatively cheaper, and widely accepted nucleophilc trifluoromethylating reagent, in the synthesis of trifluoromethylated arenes based on the pre-introduction of a trifluoromethyl group onto a “aromatic to be” substrate12345678910111213141516171819.…”

Iridium‐Catalyzed Asymmetric Allylic Aromatization Reaction

“…[7] Notably,i n2 014, the group of Carreira reported highly enantioselective allylic substitution reactions of branch cinnamyl alcohols with 1,1-disubstituted olefins using achiral Ir-(P,olefin) complex. [8] Inspired by this elegant work, we envisioned that an asymmetric allylic aromatization (AAAr) strategy might be possible for readily available methylene-substituted (hetero)cycles [9,10] as equivalents of benzylic-type nucleophiles in Ir-catalyzed asymmetric allylic substitution reactions.H owever,t he main challenge for the protocol is that the methylene-substituted (hetero)cycles, different from the 1,1-disubstituted olefins,are not stable and can aromatize under the acidic conditions required for the Carreira system.…”