Stereoselective Alkylation of Chiral Titanium(IV) Enolates with tert-Butyl Peresters

Abstract

Here, we present a new stereoselective alkylation of titanium(IV) enolates of chiral N -acyl oxazolidinones with tert -butyl peresters from Cα-branched aliphatic carboxylic acids, which proceeds through the decarboxylation of the peresters and the subsequent formation of alkyl radicals to produce the alkylated adducts with an excellent diastereoselectivity. Theoretical calculations account for the observed reactivity and the outstanding stereocontrol. Importantly, the resultant compounds can be easily converted into ligands for asymmetric and catalytic transformations.

Optimized Asymmetric Synthesis of Umuravumbolide

“…According to the retrosynthetic analysis outlined in Scheme 1 , the synthesis began with the stereoselective alkylation of the chiral α-OTBS acyl oxazolidinone 2 ( Scheme 2 ). 7 Importantly, titanium(IV) enolates from N -acyl oxazolidinones show an unexpected biradical character, which grants them a unique reacting profile. 8 Indeed, treatment of such chiral enolates with diacyl peroxides gives rise to highly diastereoselective Cα alkylations through a SET process, in which the enolate acts as a reducing agent that triggers the decarboxylation of the peroxide and the ensuing formation of an alkyl radical.…”

para-Selective radical alkylation of pyridines with diacyl peroxides and peresters

“…Therefore, we aimed at a more practical, less expensive, general solution for the Minisci-type C(4)-alkylation of pyridines and focused on diacyl peroxides as well as peresters as C-radical precursors for three reasons. [32][33][34][35][36][37][38][39][40][41][42][43] First, they are easily prepared from cheap and widely available alkyl carboxylic acids. Second, efficient O-O bond homolysis and carbon dioxide release will give ready access to alkyl radicals under heating without any additional reagent.…”

Diastereoselective access to C,C-glycosyl amino acids via iron-catalyzed, auxiliary-enabled MHAT coupling

“…Consecutively, the ( S )-enantiomer 2g was probed to be ‘mismatched’ (entry 13). The gem -dimethyl surrogate of the optimal auxiliary 27 acted as a potent inductor, but the apparent lower stability of parent acceptor 2h only enabled moderate yields (entry 14). The observation that all auxiliaries and conditions afforded the same major diastereoisomer of 5 stands in line with previous reports involving pyranosides, where the degree but not the direction of stereoselectivity could be influenced.…”