Efficient Synthesis of Chiral Trisubstituted 1,2‐Allenyl Ketones by Catalytic Asymmetric Conjugate Addition of Malonic Esters to Enynes

Abstract

An N,N'-dioxide/scandium(III) complex catalyzed, highly efficient conjugate addition of malonic esters to enynes is described. Arange of trisubstituted 1,2-allenyl ketones were obtained in high yields (up to 99 %) with good d.r.(up to 95/5) and excellent ee values (97 %-99 %). Moreover,t he products could be easily transformed into chiral furan and 5-hydroxypyrazoline derivatives,b oth of which are important skeletons of many biologically active compounds and pharmacologicals.

Asymmetric Three-Component Reaction for the Synthesis of Tetrasubstituted Allenoates via Allenoate-Copper Intermediates

“…[19][20][21][22][23][24][25] Chiral allenes represent a type of three-carbon axially chiral skeleton and have attracted increasing attention. [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] Limited examples have been reported in…”

“…asymmetric catalytic synthesis of tetrasubstituted allenes [46][47][48][49] in comparison with the achievement of di-and trisubstituted allenes. [34][35][36][37][38][39][40][41][42][43][44][45] Asymmetric nucleophilic addition with allenic ester or its isomeric compound is useful for the construction of tetrasubstituted allenic derivatives bearing both axial and central chirality. [46][47][48][49] Alleno-Mannichtype reactions via phase-transfer catalysis 46 or peptide catalysis 47 (Scheme 2, equation 1), as well as alleno-aldol-type reaction by chiral N,N 0 -dioxide/Au(III) catalysis 48 (Scheme 2, equation 2) gave aand g-regioselective products, respectively.…”

Catalytic Regio- and Enantioselective Proton Migration from Skipped Enynes to Allenes

“…[44][45][46][47][48][49][50][51][52] Catalytic enantioselective synthesis of axially chiral allenes from prochiral or racemic starting materials is a current topic of interest. [21][22][23][24][25] Representative methods in this category include (1) addition reactions to conjugated enynes or diynes, [53][54][55][56][57][58][59][60][61][62][63] (2) allylic substitution reactions or [3 + 2] cycloadditions through alkylidene p-allylpalladium intermediates, [64][65][66][67][68][69][70][71][72][73][74][75] (3) palladium-catalyzed allylic b-hydride elimination of internal enol triflates, 76 (4) nickel-catalyzed propargyl Claisen rearrangement, 77 (5) deprotonative C(sp 2 )-H functionalization of racemic allenes, [78][79][80][81] (6) alkynylogous Mukaiyama aldol reaction,…”

Catalytic asymmetric synthesis of chiral trisubstituted heteroaromatic allenes from 1,3-enynes

“…Classic approaches typically involve (kinetic) resolution of racemic allenes 4,5 or chirality transfer from optically pure propargylic precursors [6][7][8][9][10] . Recent years have witnessed a tremendous development on metal-catalyzed enantioselective synthesis of chiral allenes [11][12][13][14][15][16] , such as nucleophilic addition to 1,3-enynes [17][18][19] , enantioselective functionalization of racemic allenes [20][21][22] , β-hydride elimination from enol triflates 23 , rearrangement of propargylic compounds [24][25][26][27] , coupling of terminal alkynes with diazo compounds [28][29][30][31] , and enantioselective addition of terminal alkynes to aldehydes 32 . In addition, several asymmetric organocatalytic protocols have also been reported, such as nucleophilic addition to activated enynes 33,34 , isomerization of alkynes 35,36 , phase-transfer-catalyzed alleno-Mannich reaction 37,38 , alkynylogous Mukaiyama aldol reactions 39 , and chiral ion-pair catalysis involving a formal propargylic carbocation from racemic propargylic alcohols 40 .…”

“…1,3-Enynes can be readily prepared via Sonogashira coupling reactions 44 , and are valuable potential precursors to access allenes. However, known synthetic methods to make chiral allenes from 1,3-enynes are rather limited to reactions of activated or electron-deficient 1,3-enynes [17][18][19]33,34 , and nonactivated 1,3-enynes do not undergo these nucleophilic addition reactions due to their weak electrophilicity. Recent advances on Cu-catalyzed functionalization of alkenes indicate successful conversions of alkenes to nucleophilic alkylcopper species [45][46][47][48][49][50][51][52][53][54] .…”