A case study of the MAC (masked acyl cyanide) oxyhomologation of N,N-dibenzyl-l-phenylalaninal with anti diastereoselectivity: preparation of (2S,3S)-allophenylnorstatin esters

Abstract

The three-component reaction between a protected α-amino aldehyde, an alcohol and an α-silyloxymalononitrile provides an expedient access to protected α-hydroxy-β-amino acid derivatives. The prototypical process, performed on N-Cbz-phenylalaninal, is known...

On the Keto‐Enol‐Tautomerism of 2‐(1‐Hydroxyethylidene)malononitrile and Its Lewis Adduct Formation with B(C6F5)3

“…Most syntheses of 4 known from literature start with malononitrile, which is first deprotonated in situ [14,15,17,18] . We applied the slightly modified synthesis of Cui et al.…”

“…Most syntheses of 4 known from literature start with malononitrile, which is first deprotonated in situ. [14,15,17,18] We applied the slightly modified synthesis of Cui et al (Scheme 2). [19] That is, sodium hydride, NaH, suspended in THF and cooled to À 10 °C was treated with malononitrile dissolved in THF.…”

“…[10][11][12][13] The enol isomer 4 a (and/or 4 a', CAS number 5515- , in turn, is not commercially available but has also been described in literature. [14][15][16] Therefore, the first task was to investigate which isomers (4 a and 4 b) can be isolated or observed at all. In the next step, the adduct formation with B(C 6 F 5 ) 3 in terms of acidity and a possible EAS, as already discussed for tricyanomethane, had to be studied.…”

“…and in the literature different melting points and some varying NMR data have been reported [10–13] . The enol isomer 4 a (and/or 4 a’ , CAS number 5515‐35‐5), in turn, is not commercially available but has also been described in literature [14–16] …”

Squaramide Organocatalyzed Addition of a Masked Acyl Cyanide to β-Nitrostyrenes

“…The synthesis of MAC reagents involves an intermediate hydroxymalononitrile, allowing derivatization to various protecting groups as in Scheme (R = silyl (TBS, TIPS, TBDPS), ester (Ac and other derivatives), and acetal (MOM, EE)). − Unlike traditional umpolung reagents, the increased acidity of the methine hydrogen does not require strong alkyllithium bases to generate the acyl anion equivalent . Weak tertiary amine bases or bicarbonates are sufficient to achieve deprotonation, allowing both TBS-MAC and MOM-MAC, and to a lesser extent Ac-MAC, to be exploited in a variety of bond transformations including alkylations, ,, addition to imines ,, and aldehydes, ,− as well as conjugate addition to enones , and quinone methides . MAC has also been used as a one carbon homologue in the total synthesis of complex natural products. − Only recently has the enantioselective addition of MAC reagents been realized through the organocatalyzed addition to imines and enones and an iridium-catalyzed allylic alkylation …”