New C−C Coupling Reaction of Cyclic Nitronates with Carbon Nucleophiles. Umpolung of the Conventional Reactivity of Nitronates

Abstract

Cyclic six-membered nitronates 1 are involved in diastereoselective C-C coupling reactions with various nucleophiles in the presence of either catalytic or stoichiometric amounts of TBDMSOTf to give the previously unknown N-siloxytetrahydrooxazines. The intermediacy of N,N-bis(oxy)iminium cations was proven by NMR data.

Five‐Membered Cyclic Nitronates in C–C Coupling with 1‐(tert‐Butyldimethylsilyloxy)‐1‐methoxyethylene

“…The structures of the isoxazolidines 5a-h were unambiguously confirmed by elemental analysis as well as by 1 H, 13 C, 29 Si NMR and 2D NMR spectroscopy (COSY, HSQC and NOESY). The isoxazolidines 5a-c,g,h were characterized as individual diastereomers, whereas the nitroso acetals 5d-f were analysed as mixtures of diastereomers (see Table 1).…”

“…It was found that the workup procedure previously used for six-membered nitronates [1,2] (procedure Table 1. C-C coupling reactions of five-membered cyclic nitronates 3 with silyl ketene acetal 4.…”

“…However, the above result is one reason to expect that for C-C coupling reactions with π nucleophiles no drastic changes in reactivity will take place by switching from six-to five-membered nitronates, and thus the scope of C-C coupling reactions of five-membered nitronates with π nucleophiles will be the same as that for six-membered nitronates. [1] The second experiment in Scheme 4 can be explained by assuming that the rate of silyl transfer is much higher than the rate of C-C coupling. In this context, direct silylation of the cyclic nitronates with cationic intermediates, that is, process (c), should also be discussed [see Equation (c) in Scheme 5].…”

“…This process was performed on six-membered cyclic nitronates 1 (Scheme 1). [1,2] The reaction proceeds with the electrophilic assistance of trialkylsilyl triflates (usually TBSOTf) via the cationic intermediate 1-TBS + ·OTf -. The formation of the new C-C bond is accompanied by a reorganization of the π system of the nucleophile NuЈ-E.…”

“…[1,2] The stereochemical outcome of the reactions can be explained by distal-to-C-6 attack of the nu-tions of the nitroso acetals 5 upon action of Ac F OH/methanol or some reducing agents (H 2 /Ni Ra , LAH, Al/Hg) have been examined.…”