Rh-Catalyzed Highly Enantioselective Synthesis of Aliphatic Sulfonyl Fluorides

Abstract

Rh-catalyzed, highly enantioselective (up to 99.8% ee) synthesis of aliphatic sulfonyl fluorides was accomplished. This protocol provides a portal to a class of novel 2-aryl substituted chiral sulfonyl fluorides, which are otherwise extremely difficult to access. This asymmetric synthesis has the feature of mild conditions, excellent functional group compatibility, and wide substrate scope (51 examples) generating a wide array of structurally unique chiral b-arylated sulfonyl fluorides for sulfur(VI) fluoride exchange (SuFEx) click reaction and drug discovery.

Experimental and Theoretical Study on the Role of Monomeric vs Dimeric Rhodium Oxazolidinone Norbornadiene Complexes in Catalytic Asymmetric 1,2- and 1,4-Additions

“…The pioneering discovery by Hayashi, Carreira, and Grützmacher that chiral alkene and diene ligands enable efficient stereocontrol in asymmetric catalysis has delivered highly attractive alternatives to well-known chiral phosphorus and nitrogen ligands. − A large variety of chiral diene ligands has been developed since then. , The scope of Rh-, Ir-, or Pd-catalyzed reactions has been expanded from 1,2- and 1,4-additions at electron-poor double bonds to reductions, cycloadditions, isomerizations, rearrangements, and carbene insertions into B–H bonds among others . As far as Rh (and Ir) catalysis are concerned, the majority of studies has dealt with dinuclear catalyst precursors [Rh­(diene*)­Cl] 2 or [(Ir(diene*)Cl] 2 , while less work has been carried out with mononuclear Rh complexes.…”

Desulfonative Suzuki–Miyaura Coupling of Sulfonyl Fluorides

“…[1,[3][4][5] As highlighted in Sharpless and Arvidssons recent reviews, sulfonyl fluorides are largely inert to hydrolysis, reduction, and transition metal catalysis. [1][2][3] The SO 2 F group is often installed through transition-metal catalyzed processes, [6][7][8][9][10][11][12][13][14][15][16][17][18] and has been reported to be inert under Suzuki-Miyaura coupling (SMC) conditions. [3,[19][20][21] As a result, while sulfonyl fluorides are a powerful tool to access sulfonylated derivatives, their use as SMC electrophiles to form C À C bonds would significantly broaden their synthetic utility.…”

“…Other functional groups on the boronic acid were also found to be tolerated, including vinyl substitution (5), aromatic amines (6), benzyl ethers (8,17,24), aldehydes (10), and dioxy methylene groups (14). Pyridyl sulfonyl fluorides substituted with electron-donating or electron-withdrawing groups displayed good reactivity using Cu(IPr)Cl and KHF 2 as additives (12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Substitution ortho to the sulfonyl fluoride leaving group was tolerated (19).…”

‘Awaken’ aryl sulfonyl fluoride: a new partner in the Suzuki–Miyaura coupling reaction

“…12 III . The orthogonal reactivity of sulfonyl fluoride has been identified in the presence of transition metals, such as Cu, 13 Ir, 14 Rh, 15 and Pd (Scheme 1b). 16…”