Stereoselective Alkylation of (S)-N-Acyl-4-isopropyl-1,3-thiazolidine-2-thiones Catalyzed by (Me₃P)₂NiCl₂

Abstract

The structurally simple (Me3P)2NiCl2 complex catalyzes SN1-type alkylations of chiral N-acyl thiazolidinethiones with diarylmethyl methyl ethers and other stable carbenium cations. The former can contain a variety of functional groups and heteroatoms at the α-position. The resultant adducts are isolated as single diastereomers in high yields and can be converted into enantiomerically pure derivatives in a straightforward manner.

Direct and Enantioselective Aldol Reactions Catalyzed by Chiral Nickel(II) Complexes

“…[10] Therefore, the role of the silyl triflate is twofold, since it activates the aldehyde as well as converting the nickel(II) chloride complex into the true catalytic species. [11] The results summarized in Table 1 show that N-propanoyl thiazinanethione 1 reacts with 4methoxybenzaldehyde (a) in the presence of minute amounts of a large array of nickel(II) complexes, with the exception of DIOPNiCl 2 (Table 1, entry 2). Indeed, achiral (Me 3 P) 2 NiCl 2 provided a mixture of silyl aldol adducts with a remarkable diastereomeric ratio (dr 88:12) from which the racemic antiadduct 2 a was isolated in 79 % yield (Table 1, entry 1), whereas other chiral complexes also catalyzed the desired aldol reaction with full conversion.…”

From QCA (Quantum Cellular Automata) to Organocatalytic Reactions with Stabilized Carbenium Ions

“…Alkylation with benzodithiolylium using a supported115 catalyst, obtained also by flow conditions,116 can enhance the applicability of the alkylation for large‐scale processes. Benzodithiolylium can also be applied to general organometallic chemistry,117 enolate chemistry,118 and natural product synthesis,119 showing that this reagent can be quite versatile.…”

Diastereoselective and Catalytic α-Alkylation of ChiralN-Acyl Thiazolidinethiones with Stable Carbocationic Salts

“…19,20 As part of our studies aimed at the development of new catalytic and stereoselective carbon-carbon bond forming reactions, 21 we have recently described a nickel-catalyzed alkylation of chiral N-acyl-4-isopropyl-1,3-thiazolidine-2-thiones with diarylmethyl methyl ethers, which provide the corresponding adducts in high yields and with absolute stereocontrol. 22 Considering that the reaction involves the addition of a nickel(II) enolate to a cationic intermediate generated in situ, we thus envisaged that a related procedure based on the direct addition to naked carbenium cations 23 would avoid the need to activate the electrophile, greatly simplifying the experimental procedure and attaining a more atom economic process, and might also provide a way to introduce sterically hindered groups, a challenge that still remains elusive. Herein, we describe the direct and diastereoselective alkylation of N-acyl-4-isopropyl-1,3-thiazolidine-2-thiones with tropylium and trityl carbenium salts catalyzed by a commercially available nickel(II) complex, (Me 3 P) 2 NiCl 2 , and subsequent conversion of the resultant adducts into enantiomerically pure derivatives (Scheme 1).…”

“…Herein, we describe the direct and diastereoselective alkylation of N-acyl-4-isopropyl-1,3-thiazolidine-2-thiones with tropylium and trityl carbenium salts catalyzed by a commercially available nickel(II) complex, (Me 3 P) 2 NiCl 2 , and subsequent conversion of the resultant adducts into enantiomerically pure derivatives (Scheme 1). Applying small changes to the conditions previously employed 21,22 where the electrophile required activation, we initially assessed the addition of (S) 4-isopropyl-Npropanoyl-1,3-thiazolidine-2-thione (1a) to the stable tropylium cation, a model for naked carbenium ions, promoted by (Me 3 P) 2 NiCl 2 in the presence of 2,6-lutidine.…”

“…As previously reported, N-acyl thiazolidinethiones 1 were prepared by acylation of (S)-4-isopropyl-1,3-thiazolidine-2thione. 22,30 (S)-N- Hz). 13 C NMR (CDCl 3 , 100.6 MHz) δ 202.7 (C), 176.9 (C), 131.0 (CH), 130.6 (CH),…”