Stereocontrolled alkylation of unsaturated compounds with alkoxytitanacyclopropane reagents

Abstract

Interaction of titanium(IV) isopropoxide with ethylmagnesium bromide and its higher homologs leads to the generation of alkoxytitanacyclopropane species, which are able to act in the reactions with unsaturated compounds as 1,2-dicarbanionic alkylating agents. The present review is focused on the processes of intermolecular regio- and stereoselective alkylation of carboxylic esters and allylic alcohol derivatives with alkoxytitanacyclopropane reagents. The oxophilicity of the titanium atom and its tendency to form sterically crowded ate complexes are probably the main factors providing a high level of selectivity of these transformations.

Stereoselective Alkylation of Allylic Alcohols: Tandem Ethylation and Functionalization

“…We report herein a stereoselective alkylation reaction of allylic alcohols by trapping of the presumed alkyltitanium intermediates with suitable electrophiles. This formal S N 2' ethylation reaction by the ethyl Grignard reagent was first reported by the Kulinkovich group, [5] and the stereochemical studies revealed the overall suprafacial stereochemical outcome is due to syn addition of the Kulinkovich reagent through a TiÀO tether and subsequent syn b elimination. [5d,e,6] Our mechanistic analysis implicated the generation of an alkyltitanium intermediate 4 by way of b elimination of 3 at the penultimate stage, which prompted us to investigate in situ elaboration of 4 to broaden the scope of this allylation reaction ( Table 1).…”

“…This formal S N 2' ethylation reaction by the ethyl Grignard reagent was first reported by the Kulinkovich group, [5] and the stereochemical studies revealed the overall suprafacial stereochemical outcome is due to syn addition of the Kulinkovich reagent through a TiÀO tether and subsequent syn b elimination.…”

“…(1); El = H]. [4][5][6] The synthetic utility of the low-valent titanium (Kulinkovich reagent) [4] mediated alkylation would be greatly enhanced by an in situ introduction of a functionalized side chain (El ¼ 6 H). We report herein a stereoselective alkylation reaction of allylic alcohols by trapping of the presumed alkyltitanium intermediates with suitable electrophiles.…”

Stereoselective Alkylation of Allylic Alcohols: Tandem Ethylation and Functionalization

“…This formal S N 2′ ethylation reaction by the ethyl Grignard reagent was first reported by the Kulinkovich group,5 and the stereochemical studies revealed the overall suprafacial stereochemical outcome is due to syn addition of the Kulinkovich reagent through a TiO tether and subsequent syn β elimination 5d,e,6. Our mechanistic analysis implicated the generation of an alkyltitanium intermediate 4 by way of β elimination of 3 at the penultimate stage, which prompted us to investigate in situ elaboration of 4 to broaden the scope of this allylation reaction (Table 1).…”