Distal Allylic/Benzylic C−H Functionalization of Silyl Ethers Using Donor/Acceptor Rhodium(II) Carbenes

Abstract

Regio‐ and stereoselective distal allylic/benzylic C−H functionalization of allyl and benzyl silyl ethers was achieved using rhodium(II) carbenes derived from N‐sulfonyltriazoles and aryldiazoacetates as carbene precursors. The bulky rhodium carbenes led to highly site‐selective functionalization of less activated allylic and benzylic C−H bonds even in the presence of electronically preferred C−H bonds located α to oxygen. The dirhodium catalyst Rh2(S‐NTTL)4 is the most effective chiral catalyst for triazole‐derived carbene transformations, whereas Rh2(S‐TPPTTL)4 works best for carbenes derived from aryldiazoacetates. The reactions afford a variety of δ‐functionalized allyl silyl ethers with high diastereo‐ and enantioselectivity. The utility of the present method was demonstrated by its application to the synthesis of a 3,4‐disubstituted l‐proline scaffold.

Hexafluoroisopropanol for the Selective Deactivation of Poisonous Nucleophiles Enabling Catalytic Asymmetric Cyclopropanation of Complex Molecules

“…Very small quantities were found to enhance the enantioselectivity of rhodium-catalyzed allylic C−H functionalization with 4-aryl-Nsulfonyl triazoles. 33 During recent studies to optimize some specific rhodium-catalyzed cyclopropanation, we discovered that HFIP (10 equiv) desensitizes the reaction to water and N,N′-dimethylaminopyridine (DMAP). 7,34 Given this exciting and unexpected result, we suspected that we could leverage this effect to deactivate a wide range of other nucleophilic poisons and reactive functionality that typically interfere with the cyclopropanation reaction.…”

“…41−45 In this study, good reactivity was generally observed with oxygen nucleophiles at low levels of HFIP (Table 3b). Substrates including acetone (32), nitromethane (33), and phenylisocyanate (34) were all tolerated without the use of HFIP. However, more nucleophilic compounds, like N,N′-dimethylformamide (DMF, 39) required 10 equiv HFIP to ensure compatibility.…”

“…We have recently become interested in exploring the role of HFIP as an additive in rhodium carbene chemistry. Very small quantities were found to enhance the enantioselectivity of rhodium-catalyzed allylic C–H functionalization with 4-aryl- N -sulfonyl triazoles . During recent studies to optimize some specific rhodium-catalyzed cyclopropanation, we discovered that HFIP (10 equiv) desensitizes the reaction to water and N,N ′-dimethylaminopyridine (DMAP). , Given this exciting and unexpected result, we suspected that we could leverage this effect to deactivate a wide range of other nucleophilic poisons and reactive functionality that typically interfere with the cyclopropanation reaction. ,, HFIP can hydrogen bond with, or even formally protonate, different nucleophiles due to its relatively high acidity, preventing them from coordinating with the dirhodium catalyst and the rhodium carbene intermediate .…”