Ti-Catalyzed Dehydroxylation of Tertiary Alcohols

Abstract

Herein we report a Ti-catalyzed direct dehydroxylation of tertiary aliphatic alcohols under mild reaction conditions, forging Barton-type deoxygenation products. This protocol tolerates a wide range of functional groups, including primary alkyl chloride and carbonyl groups. It allows for selective dehydroxylation of tertiary alcohols in diols and the formation of deuterated products with moderate deuterium incorporation. The efficient modification of several drugs and natural products (or their derivatives) highlights the synthetic utility of this method.

Titanium-catalysed deoxygenation of benzylic alcohols and lignin model compounds

“…Based on our observations and literature examples, 15–18 we propose a Ti( iii )/Ti( iv ) reaction mechanism for the deoxygenation of benzylic alcohols (Scheme 7d). The catalytically active Ti( iii ) species is generated by the reduction of the precatalyst with Mn followed by the formation of complex III , which undergoes a homolytic cleavage of the C–O bond providing complex IV and the benzyl radical, which abstracts H-atom from the silane.…”

“…Most notable is the report of Wu and co-workers on the reduction of various oxo functionalities to the corresponding hydrocarbon compound by using ammonium borane as H-donor and MeOLi as regenerating agent, 16 and the work of Chen and co-workers, in which tertiary alcohols were selectively reduced using CpTiCl 3 as precatalyst, a silane as H-atom donor and triethylsilyl chloride as regenerating agent. 17…”

“…Most notable is the report of Wu and co-workers on the reduction of various oxo functionalities to the corresponding hydrocarbon compound by using ammonium borane as H-donor and MeOLi as regenerating agent, 16 and the work of Chen and co-workers, in which tertiary alcohols were selectively reduced using CpTiCl 3 as precatalyst, a silane as H-atom donor and triethylsilyl chloride as regenerating agent. 17 Driven by the aim to find an atom-economical and environmentally friendly deoxygenation procedure with a complementary substrate scope, we developed a new Ti/silane system, in which the same silane should act both as hydrogen donor and regeneration agent for the Ti-catalyst. We started the investigation by choosing Cp 2 TiCl 2 as the precatalyst.…”

Titanium-catalysed deoxygenation of benzylic alcohols and lignin model compounds

“…But it is evident that in contrast to related methods, which require additional activating agents such as TMSCl 14 or LiOMe, 16 the more Lewis acidic silane has additional role beside being the H-donor. Based on our observations and literature examples, [15][16][17][18] we propose a Ti(III)/Ti(IV) reaction mechanism for the deoxygenation of benzylic alcohols (Scheme 7d). The catalytically active Ti(III) species is generated by the reduction of the precatalyst with Mn followed by the formation of complex III, which undergoes a homolytic cleavage of the C-C bond providing complex IV and the benzyl radical, which abstracts H-atom from the silane.…”

“…Most notable is the report of Wu and co-workers on the reduction of various oxo functionalities to the corresponding hydrocarbon compound by using ammonium borane as H-donor and MeOLi as regenerating agent, 16 and the work of Chen and co-workers, in which tertiary alcohols were selectively reduced using CpTiCl3 as precatalyst, a silane as H-atom donor and triethylsilyl chloride as regenerating agent. 17 Driven by the aim to find an atom-economical and environmentally friendly deoxygenation procedure with a complementary substrate scope, we developed a new Ti/silane system, in which the same silane should act both as hydrogen donor and regeneration agent for the Ti-catalyst. We started the investigation by choosing Cp2TiCl2 as the precatalyst.…”