Consecutive C1‐Homologation / Displacement Strategy for Converting Thiosulfonates into O,S‐Oxothioacetals

Abstract

A conceptually intuitive synthesis of oxothioacetals is reported starting from thiosulfonates as electrophilic sulfur donors. The installation of a reactive CH 2 Cl motif with a homologating carbenoid reagent, followed by the immediate nucleophilic displacement with alcoholic groups [(hetero)-aromatic, aliphatic] offer a convenient access to the title compounds. Genuine chemoselectivity is uniformly observed in the case of multi-functionalized systems.

Aza-Matteson Reactions via Controlled Mono- and Double-Methylene Insertions into Nitrogen–Boron Bonds

“…Note that aminoboranes can be easily prepared from mixing and heating the corresponding free amines and HBpin without purification . After extensive optimization (for details, see the Supporting Information, Table S1), when treating aminoborane 1a with carbenoid CH 2 BrLi, generated in situ from CH 2 Br 2 and n BuLi, at −78 °C, followed by adding ZnCl 2 (0.5 equiv), an unexpected double-methylene-insertion product 2a was selectively formed in high yield. Because the β-aminoalkylboronate was difficult to directly isolate via chromatography, an in situ oxidation to the corresponding alcohol ( 3a ) was carried out for the convenience of the yield calculation.…”

Base-mediated homologative rearrangement of nitrogen–oxygen bonds of N-methyl-N-oxyamides

“…8 In the course of our studies on programmable LiCH 2 X-mediated homologation of carbon electrophiles, 9 we validated the rationale for the selective insertion of methylene units into chalcogenide bonds (S–S and Se–Se analogues) to construct geminal disulfurated methanes (dithioacetal-like – Scheme 1c). 10 One intriguing aspect is whether a C1-insertion could take place selectively on a more sophisticated Z–X–Y platform, where both Z–X and X–Y bonds might undergo homologation (Scheme 1d): to the best of our knowledge, these clusters have not been previously investigated in C1-insertion sequences. In this context, N -alkoxy-substituted amides 11 constitute representative models since both the C(O)–N and the N–O fragments could be subjected to the methylene insertion: as documented in recent work by our group, 12 amide-type substrates undergo homologation (employing [M]-CH 2 -LG reagents) at the C(O)–N linkage – yielding α-substituted ketones 11 b ,12 c ,13 – thus, precluding de facto the use of such agents for inserting the C1-unit within the N–O bond (Scheme 1d – up).…”

Halogen‐Imparted Reactivity in Lithium Carbenoid Mediated Homologations of Imine Surrogates: Direct Assembly of bis‐Trifluoromethyl‐β‐Diketiminates and the Dual Role of LiCH2I

“…Generating LiCH 2 I with n-BuLi-LiBr benefited the formation of 2 (entry 3), though the addition of the facilitating lithiating ligand TMEDA inverted the ratio in favour of 3 (entry 4). Switching to other common organolithiums (s-BuLi-LiBr and t-BuLi-LiBr) had little effect on the reaction outcome (entries 5,6) while, bromomethyllithium (LiCH 2 Br, [16] generated from BrCH 2 I and MeLi-LiBr) could be used as a competent C1-unit donor (entry 7), giving 2 in slightly lower yield. Pleasingly, these experimental evidences-that is, different homologating behaviour of both LiCH 2 I and LiCH 2 Br compared with LiCH 2 Cl reported before-fully support the hypothesized logic harnessed on rendering further reactive the TI.…”