Enantioselective Copper-Catalyzed Arylation-Driven Semipinacol Rearrangement of Tertiary Allylic Alcohols with Diaryliodonium Salts

Abstract

A copper-catalyzed enantioselective arylative semipinacol rearrangement of allylic alcohols using diaryliodonium salts is reported. Chiral Cu(II)-bisoxazoline catalysts initiate an electrophilic alkene arylation, triggering a 1,2-alkyl migration to afford a range of nonracemic spirocyclic ketones with high yields, diastereo- and enantioselectivities.

Enhanced Reactivity by Torsional Strain of Cyclic Diaryliodonium in Cu-Catalyzed Enantioselective Ring-Opening Reaction

“…[39][40][41][42][43][44][45] Diaryliodoniums act as powerful reagents for arylation of nucleophiles in both asymmetric and non-asymmetric reactions, most notably in contributions from the Gaunt group. [46][47][48][49][50][51][52][53] We reasoned that the ring-opening reaction of cyclic diaryl iodoniums would give atropisomeric aryl iodides, which represent an ideal class of precursors for the divergent synthesis of biaryl atropisomers (Scheme 1E). [54][55][56][57][58][59] The key challenges, however, are (1) how to increase the reactivity, because cyclic diaryliodoniums showed significantly lower activity than noncyclic reagents, 57 and (2) how to avoid the formation of diamination products or carbazoles.…”

Ni(II)-catalyzed asymmetric alkenylations of ketimines

“…However, the ( n + 2)-expansion of larger vinyl cyclic compounds remains challenging due to the fact that they possess less ring strain than their smaller ring counterparts, an essential driving force for ring expansion 63 . Furthermore, the asymmetric synthesis of chiral compounds via this ring ( n + 2)-expansion has not been widely reported, possibly due to the lack of interactions between the alkenyl group and chiral catalyst that would allow for the remote control of the attacking enantioface at the β-carbon of the C=C bond 64 – 66 . Njardarson reported a chiral acid-catalyzed asymmetric ring ( n + 2)-expansion of dialkenyl oxetane with only one substrate, requiring a low temperature and long reaction time to obtain the desired product with good ee and moderate yield 67 .…”

Copper‐Catalyzed Enantioselective Domino Arylation/Semipinacol Rearrangement of Allylic Alcohols with Diaryliodonium Salts

“…In the presence of an appropriate chiral ligand, one should be able to differentiate the two faces of the double bond, achieving therefore the enantioselective aryl transfer. A recent paper from Gaunt's group on the same subject prompted us to communicate our own results herein . Spirocycloalkanones obtained in this process are privileged scaffolds in the development of chiral ligands/organocatalysis and are known precursors for the synthesis of acetylcholinesterase and monoamine oxidase…”

“…Ar ecent paper from Gaunt's group on the same subjectp romptedu st oc ommunicate our own resultsh erein. [11] Spirocycloalkanones obtained in this process [12] are privileged scaffoldsi nt he development of chiral ligands/organocatalysis [13] anda re known precursors for the synthesis of acetylcholinesterase and monoamineo xidase. [14] Arylative semipinacolr earrangement of 1-(1H-inden-3-yl)cyclobutan-1-ol (1a)w ith mesityl(phenyl)iodonium trifluoromethanesulfonate (2a)w as chosen as ab enchmarkr eaction.…”

“…Using bidentate (S,S)-diphenylbisoxazoline L2 as ligand under otherwise identical conditions provided the desired product 3a in 67 %y ield, albeit with only 9% ee (entry2). With L5,t he ligand of choice in Gaunt's work, [11] 3a was isolated in 65 %y ield with 52 % ee under these non-optimizedc onditions. Further experiments revealed that bisoxazoline L8 derived from (1R,2S)-2-amino-1,2-diphenylethan-1-ol was the most effective (entry 9) leadingt o3a in 75 %y ield with ee of 75 %and 74 %, respectively,for the two diastereoisomers.T he influence of different counteranions of the diaryliodoniums alts on the reaction outcomew as next examined (en-Scheme1.Dominoarylation/semipinacol rearrangement of allylica lcohols.[a] Dr.…”