Copper‐Catalyzed Coupling Reaction of Secondary Alkyl 2‐Pyridinesulfonates with Alkyl Lithium‐Based Reagents

Abstract

The Cu(OTf)2‐catalyzed alkyl–alkyl coupling reaction of a secondary substrate MeCH(OSO2Py)CH2CH2C6H4(4‐OMe) with a nBuLi‐based reagent prepared by transmetalation with MgBr2 ⋅ THF3 in THF produced a coupling product in 74 % yield. The use of soluble MgBr2 ⋅ THF3 in THF was required for this reaction. This method was applied to sBuLi and Ph(CH2)4Li. In contrast, transmetalation of MeLi with soluble MgCl2 ⋅ THF2 in THF produced the Me reagent, which was reactive for the coupling reaction. The reaction proceeded with inversion of the stereogenic carbon. Furthermore, (S)‐14‐methyloctadecan‐2‐one, a sex pheromone produced by lichen moths, was synthesized.

Enantioselective Synthesis of the Active Sex Pheromone Components of the Female Lichen Moth, Lyclene dharma dharma, and Their Enantiomers

“…They then employed the Wittig reaction, alkylation of alkynes, and acetoacetic ester synthesis to construct sex pheromone components in Lyclene dharma dharma from ( S )- and ( R )-citronellal; they synthesized ( S )- 1 with a total yield of 11% in 15 steps, ( S )- 2 with a total yield of 10% in 13 steps [ 6 ]. In 2023, Kobayashi and colleagues reported the synthesis of ( S )-14-methyloctadecan-2-one with a total yield of 10% in seven steps, using ( S )-3-butyn-2-ol as a chiral starting material, with a copper-catalyzed coupling reaction of alkynyl 2-pyridyl sulfonate and an alkyl lithium reagent as the key reaction [ 7 ]. The reported synthetic routes still have some shortcomings, such as difficult synthetic routes, expensive chiral starting materials, complex synthetic operations, and poor overall yields.…”

“…Molecules 2024, 29, 2918 2 of 14 2-one with a total yield of 10% in seven steps, using (S)-3-butyn-2-ol as a chiral starting material, with a copper-catalyzed coupling reaction of alkynyl 2-pyridyl sulfonate and an alkyl lithium reagent as the key reaction [7]. The reported synthetic routes still have some shortcomings, such as difficult synthetic routes, expensive chiral starting materials, complex synthetic operations, and poor overall yields.…”