Rhodium‐Catalyzed Enantioselective Radical Addition of CX₄ Reagents to Olefins

Abstract

We describe the synthetically useful enantioselective addition of Br À CX 3 (X = Cl or Br) to terminal olefins to introduce at rihalomethyl group and generate optically active secondary bromides.C omputational and experimental evidence supports an asymmetric atom-transfer radical addition (ATRA) mechanism in which the stereodetermining step involves outer-sphere bromine abstraction from a[ (bisphosphine)Rh II BrCl] complex by ab enzylic radical intermediate. This mechanism appears unprecedented in asymmetric catalysis.Radical addition reactions to olefins can effectively increase molecular complexity.F or example,i n1 945 Kharasch described the addition of CX 4 across terminal olefins to form an ew C À Cb ond, introduce an ew CX 3 group,a nd generate an ew CÀXb ond (Scheme 1a). [1] This addition generally Scheme 1. Addition of CX 4 reagents to olefins. Angewandte Chemie CommunicationsScheme 2. Mechanisms of asymmetric radical reactions. a) Radical addition to ametal-coordinated substrate. b) Oxidation of chiral enamine intermediates, followed by radical trapping. c) Metal capture of radical intermediates, followed by reductive elimination.d )Outersphere ligand abstraction by aprochiral radical.Scheme 3. Discovery of an enantioselective Kharasch reaction. cod = 1,5-cyclooctadiene.

A Copper Catalyst with a Cinchona‐Alkaloid‐Based Sulfonamide Ligand for Asymmetric Radical Oxytrifluoromethylation of Alkenyl Oximes

“…[1] In this respect, transition-metalcatalyzed intermolecular addition of radical species to alkenes to realize 1,2-difunctionalization has emerged as one of the most attractive strategies for the construction of two vicinal chemical bonds. [3][4][5] In particular,Buchwald and Liu pioneered the use of aneutral chiral Cu/bis(oxazoline) system to elegantly realize enantioselective alkene difunctionalizations (Scheme 1(i)). [3][4][5] In particular,Buchwald and Liu pioneered the use of aneutral chiral Cu/bis(oxazoline) system to elegantly realize enantioselective alkene difunctionalizations (Scheme 1(i)).…”

“…[2] However,t here have been limited catalytic systems for the enantioselective control of free alkyl radical species. [3][4][5] In particular,Buchwald and Liu pioneered the use of aneutral chiral Cu/bis(oxazoline) system to elegantly realize enantioselective alkene difunctionalizations (Scheme 1(i)). [4] At the same time,o ur group has also developed acopper/chiral anionic phosphate system to realize asymmetric transformations (Scheme 1(ii)).…”

Recent Developments in the Polychloroalkylation by Use of Simple Alkyl Chlorides

“…In 2017, the first example of enantioselective Rhodium‐catalyzed atom‐transfer radical addition to terminal styrene is described by Ready and co‐workers (Scheme 16). [17] This method could realize the construction of optically active benzyl bromide and trichloromethyl group with excellent enantioselectivity and yield at −78 °C in the presence of [Rh(cod)Cl] 2 and bidentate phosphine ligand.…”

“…Recently, with the development of radical chemistry, simple alkyl chlorides (such as dichloromethane, chloroform etc.) have been used as effective precursors to introduce the polychlorinated groups through the coupling with alkanes, [4–7] addition of olefins [9–26] and cyclizations [27–36] . Among them, due to the high reactivity of polychlorinated radical intermediates, the radical‐mediated polychloroalkylation groups have been considered to be an indispensable tool for the synthesis of complex polychlorinated compounds.…”

“…In the past few decades, transition‐metal‐catalyzed (Ru, Rh, Cu, Nb, etc. ), [4,11–17] photoredox catalyzed, [5–6,10,14] and oxidative radical functionalization reactions play an important role in the synthesis of polychlorinated compounds. This review focuses on recent impressive progress in polychloromethylation or polychloroalkylation, highlighting the radical process, initiated by simple alkyl chlorides.…”