Enantioselective Intramolecular Iridium-Catalyzed Cyclopropanation of α-Carbonyl Sulfoxonium Ylides

Abstract

Enantioselective cyclopropanation of α-carbonyl sulfoxonium ylides (SY) has so far been limited to addition/ring closure reactions on electron-poor olefins. Herein, we report the iridium-catalyzed intramolecular cyclopropanation of SY in the presence of a chiral diene in up to 96% yield and 98% enantioselectivity. Moreover, density functional theory calculations suggest that the re face of the olefin preferably attacks an iridium carbene intermediate in an asynchronous concerted step that is independent of the geometry of the olefin.

HTE and machine learning-assisted development of iridium(i)-catalyzed selective O–H bond insertion reactions toward carboxymethyl ketones

“…A possible reaction mechanism was proposed and is shown in Scheme S1† based on the above results and literature precedents. 9…”

“…As iridium( i ) complexes are versatile catalysts in many reactions of sulfoxonium ylides, 9 iridium carbene species have become important for efficiently constructing various functional molecules from sulfoxonium ylides. By combining high-throughput experimentation (HTE) and machine learning (ML) technologies, 10,11 herein, we disclose the development of an efficient approach for the selective formation of a wide range of (hetero)carboxymethyl ketones through iridium( i )-catalyzed O–H bond insertion of carboxylic acids and sulfoxonium ylides (Scheme 1D).…”

Cyclic Sulfoxonium Ylides: Synthesis and Chemospecific Reactivity in the Catalytic Alkylation of Indoles

“…The decreased reactivity of 16 as compared to that of 3 might be understood by considering Mayr's nucleophilicity scale, which suggests that the lactone 3 should be more nucleophilic than the ketone 16 [23,24] . Although recent theoretical studies suggest that the formation of metal carbenes from α‐carbonyl sulfoxonium ylides is a two‐step process involving facile coordination of the ylide carbon atom to the metal followed by rate‐limiting elimination of DMSO, [25] the efficiency of formation of an iridium carbene from 3 , 9 , 15 , and 16 does not appear to fully explain their difference of reactivity [18–21,26–28] . Instead, it is more likely that after attack of the iridium catalyst by these substrates and elimination of DMSO from 58 , iridium carbenes 59 would be formed in all cases (Figure 1c).…”

“…However, the reaction is sensitive to electronic variation in the cyclic sulfoxonium ylides as 5-OMe and 5-Cl derivatives 10 and 12 gave 49 and 50 in high yields, respectively, whereas more electron-rich ylide 11 gave 51 in 50 % yield only. We also conducted the reaction in the presence of a chiral iridium catalyst that previously gave positive results in the intramolecular cyclopropanation of sulfoxonium ylides, [21] but no induction of enantioselectivity was observed in the reaction of N-Me indole and ylide 9 (Figure 1). Finally, it is noteworthy that the cyclic sulfoxonium ylides used in this iridium-catalyzed alkylation of indoles appear to be more ChemCatChem reactive than their acyclic congeners under the same conditions, as shown with compounds 52 and 53 (Figure 2).…”

“…[23,24] Although recent theoretical studies suggest that the formation of metal carbenes from α-carbonyl sulfoxonium ylides is a two-step process involving facile coordination of the ylide carbon atom to the metal followed by rate-limiting elimination of DMSO, [25] the efficiency of formation of an iridium carbene from 3, 9, 15, and 16 does not appear to fully explain their difference of reactivity. [18][19][20][21][26][27][28] Instead, it is more likely that after attack of the iridium catalyst by these substrates and elimination of DMSO from 58, iridium carbenes 59 would be formed in all cases (Figure 1c). Then, ChemCatChem dimerization [21,26] and other unidentified decomposition pathways would be predominant in the case of the six-membered ring intermediates (n = 1), whereas indole would react productively with the five-membered ring intermediates 59 (n = 0) to give 60, which would give 33 and 37 after a sequence consisting of 1,2-hydride shift to 61, elimination to 62 and rearomatization.…”