Enantioselective Trifluoromethylthiolating Lactonization Catalyzed by an Indane‐Based Chiral Sulfide

Abstract

Enantioselective trifluoromethylthiolation, especially of alkenes,i sachallenging task. In this work, we have developed an efficient approach for enantioselective trifluoromethylthiolating lactonization by designing an indane-based bifunctional chiral sulfide catalyst and as helf-stable electrophilic SCF 3 reagent. The desired products were formed with diastereoselectivities of > 99:1 and good to excellent enantioselectivities.T he transformation represents the first enantioselective trifluoromethylthiolation of alkenes and the first enantioselective trifluoromethylthiolation that is enabled by ac atalyst with aL ewis basic sulfur center.

Catalytic Enantioselective Construction of Chiral Benzo-Fused N -Heterocycles through Friedel–Crafts-Type Electrophilic Chlorination

“…Based on previous experience with asymmetric reactions catalyzed by chiral chalcogenides, 49,[63][64][65][66][67][68][69][70][71] we set out to test asymmetric chlorocarbocyclization of N-cinnamyl aniline compound 1 using chiral chalcogenide catalysts in the presence of acid (Table 1). Generally, allyl anilide 1 was easily prepared from the corresponding anilines in two steps.…”

Copper-Catalyzed Enantioselective Trifluoromethylthiolation of Secondary Propargyl Sulfonates

“…[1][2][3][4][5] Over the past decade, various methods have emerged in the site-selective introduction of CF 3 S into organic molecules, [6][7][8][9][10] most of which are focused on the construction of C sp 2 -SCF 3 bonds. [6][7][8][9][10][11][12][13][14][15][16] In contrast, the asymmetric construction of C sp 3 -SCF 3 bonds at the stereogenic center has received less attention and remains underdeveloped, [17][18][19][20][21][22][23] although these chiral compounds would have substantial impacts on research and development of new drugs. To date, asymmetric electrophilic trifluoromethylations have been developed, in which organocatalysts [17][18][19][20][21]24,25 or Lewis acids 26 are used to enantioselectively catalyze the formation of the C sp 3 -SCF 3 bond at the stereogenic center (Schemes 1a and 1b).…”

“…[6][7][8][9][10][11][12][13][14][15][16] In contrast, the asymmetric construction of C sp 3 -SCF 3 bonds at the stereogenic center has received less attention and remains underdeveloped, [17][18][19][20][21][22][23] although these chiral compounds would have substantial impacts on research and development of new drugs. To date, asymmetric electrophilic trifluoromethylations have been developed, in which organocatalysts [17][18][19][20][21]24,25 or Lewis acids 26 are used to enantioselectively catalyze the formation of the C sp 3 -SCF 3 bond at the stereogenic center (Schemes 1a and 1b). Despite the importance of these asymmetric trifluoromethylthiolation methods, their substrates are restricted to carbonyl compounds [17][18][19][20][24][25][26] or alkenes, 21,[27][28][29] limiting their widespread applications in discovering new chiral bioactive molecules.…”

“…To date, asymmetric electrophilic trifluoromethylations have been developed, in which organocatalysts [17][18][19][20][21]24,25 or Lewis acids 26 are used to enantioselectively catalyze the formation of the C sp 3 -SCF 3 bond at the stereogenic center (Schemes 1a and 1b). Despite the importance of these asymmetric trifluoromethylthiolation methods, their substrates are restricted to carbonyl compounds [17][18][19][20][24][25][26] or alkenes, 21,[27][28][29] limiting their widespread applications in discovering new chiral bioactive molecules. Thus, the development of new strategies to stereoselectively synthesize diversified chiral trifluoromethylthiolated compounds is highly desirable.…”

Selenide-catalyzed enantioselective synthesis of trifluoromethylthiolated tetrahydronaphthalenes by merging desymmetrization and trifluoromethylthiolation

“…Continuing our interest in Lewis basic selenium 54 – 62 -catalyzed trifluoromethylthiolation 19 , 20 , 63 – 65 , we intended to produce chiral CF 3 S molecules with an all-carbon quaternary stereocenter through an enantioselective, electrophilic desymmetrization, and trifluoromethylthiolation mode. We envisioned that when gem -diaryl-tethered alkenes were employed as the substrates, the aryl group on substrate could act as a nucleophile to attack chiral selenide-captured trifluoromethylthiiranium moiety to directly afford chiral CF 3 S tetrahydronaphthalenes (Fig.…”