Approaches to α-amino acids via rearrangement to electron-deficient nitrogen: Beckmann and Hofmann rearrangements of appropriate carboxyl-protected substrates

• Sosale Chandrasekhar and
• V. Mohana Rao

Beilstein J. Org. Chem. 2012, 8, 1393–1399, doi:10.3762/bjoc.8.161

• two approaches to amino acids in which the key step is either the Beckmann or the Hofmann rearrangement, as described in the following. Results and Discussion Beckmann rearrangement approach The key substrate is the known 3-phenacyl-2,4,10-trioxaadamantane (1, Scheme 1) [14][15][16]. (An improved

• transformation of 1 to 5 indicates that 1 functions as a glycine enolate equivalent with the benzoylamino group in 5 being introduced in umpolung fashion (reaction involves the migration to an electrophilic nitrogen center). Hofmann rearrangement approach Our strategy was based on the known ethyl

• reasons. The conversion of acids 8 to their amides was carried out via initial activation with DCC (dicyclohexylcarbodiimide) and pentafluorophenol in ethyl acetate solution; this was followed by reaction with ammonia gas at −20 °C. The carboxamides 9, substrates for the key Hofmann rearrangement step