Regioselective cycloadditions of N-protonated azomethine ylides and 2-azaallyl anions generated from N-(silylmethyl) thioimidates, synthetic equivalents of nonstabilized nitrile ylides

Abstract

Trimethylsilylmethyl isothiocyanate (I) reacts consecutively with the Grignard compounds (II) and the halides (III) to form the thioimidates (IV).

Synthesis of γ-Amino Acid Esters by 1,4-Addition of Deprotonated α-Aminonitriles and α-(Alkylideneamino)nitriles to α,β-Unsaturated Esters

“…The selectivity of this side reaction can be explained by the fact that anti-4 adopts an extended conformation (Figure 1), whereas in the syn-diastereomer, the repulsion between the band the Whereas the non-destructive deprotonation of a-aminonitriles with free NH protons requires the presence of a stabilizing a-substituent such as an aromatic, heteroaromatic or olefinic group in order to prevent a retro-Strecker reaction, 22 a-(alkylideneamino)nitriles 5 are much more CHacidic and can be easily deprotonated even if no stabilizing a-substituent is present. [23][24][25] We tested several conditions for the addition reaction and found that either phasetransfer conditions (7.9 M KOH/CH 2 Cl 2 , 10 mol% BnNEt 3 Cl) 26,27 or the use of metal-free bases such a DBU or Me 4 NOH furnishes the desired products. In most cases, the biphasic system gives somewhat higher yields although side reactions may occur.…”

Cycloadditions of Nonstabilized2-Azaallyllithiums (2-Azaallyl Anions) and Azomethine Ylides withAlkenes: [3+2] Approaches to Pyrrolidinesand Application to Alkaloid Total Synthesis

“…9 Again, the intermediate is a less-stabilized 2-azaallyl anion, i.e., 24, although some stabilization by the sulfur substituent may be involved. However In 1987, the same group reported the desilylation of thioimidates such as 23 in the presence of electron-poor alkenes to afford pyrrolines such as 25 (Scheme 7).…”

“…9 We have found it possible to generate 2-azaallyllithiums bearing heteroatoms such as oxygen, sulfur, and nitrogen by tin-lithium exchange on imidates, thioimidates, and amidines such as 93-95 (Scheme 22). 9,11 Only Tsuge, Kanemasa, and co-workers have reported nonstabilized 2azaallyl anions bearing a heteroatom (sulfur), although their cycloadditions appear to be limited to electron-poor alkenes (see Scheme 7 above).…”

Cycloadditions of Nonstabilized 2‐Azaallyllithiums (2‐Azaallyl Anions) and Azomethine Ylides with Alkenes: [3 + 2] Approaches to Pyrrolidines and Application to Alkaloid Total Synthesis.

“…In 1987, the same group reported the desilylation of thioimidates such as 23 in the presence of electron-poor alkenes to afford pyrrolines such as 25 (Scheme 7). 9 Again, the intermediate is a less-stabilized 2-azaallyl anion, i.e., 24, although some stabilization by the sulfur substituent may be involved. Only electron-deficient alkenes were reported to undergo cycloadditions with these anions.…”