Schmidt rearrangement regioselectivity

The Schmidt rearrangement of optically active a,a-bisalkylated 3-keto esters (161) regioselectively proceeds to give N-acyl a-alkylated a-amino acid esters (162) with retention of configuration and little or no racemization." Acid hydrolysis of (162), followed by treatment with propylene oxide, affords a-alkylated a-amino acids (163) in high yield and optical purity (equation 48). 

Krow GR, Szczepanski SW, Kim JY, Liu N, Sheikh A, Xiao Y, Yrran J (1999) Regioselective functionalization. 7.1 Unexpected prefaences for bridgehead migration in Schmidt rearrangement syntheses of novel 2,6-diazabicyclo[3.2.x]alkan-3-ones (x = 1-3). J Org Chem 64(4) 1254-1258... 

Thienobenzazocine 179 is formed regioselectively in 65-93% yield when the rearrangement is carried out in PPA or PPA in xylene. The use of H2SO4 or PCI5 gives a mixture of regioisomers 179 180 in ratios from 90 10 to 60 40. The Schmidt reaction forms only thienobenzazocine 179 in 25-65% yield from benzo[4,3]-cyclohepta[l,2- 7]thiophen-4-one 181 (Scheme 50). 

Tetramethoxy-5,6,ll,12-tetrahydrodibenzo[ ,i ]cycloocten-5-one 302 was reacted with hydroxylamine-O-sulfonic acid and underwent a one-pot Beckmann (formic acid, reflux) or Schmidt (DMF, reflux) rearrangement to afford the 6-oxodibenzo[, /]-azonine 304 (Equation 42). Regioselectivity of the process was assigned based on H NMR data and on model reactions to prove preferential migration of the 3,4-dimethoxyphenyl over the 3,4-dimethoxybenzyl group <1996T8063>. 

Acetyl-3-arylsydnones (164) undergo the regioselective Schmidt reaction to give 3-arylsydnone-4-A -methylcarboxamides (165) in good yields without formation of 4-acetamidosydnones (equation 49). In contrast to this, the Beckmann rearrangement of the oxime of (164, Ar = phenyl) does not proceed at all. 

Thiazolidine rings are normally easy to prepare but this year a new reaction has appeared in which the ring system was produced during a thermally-induced intramolecular eliminative rearrangement. The azido-enones (364) were heated to 140 C leading to a mixture of the products (365) and (366) in equal proportions. The authors have determined that an intramolecular acid-catalysed Schmidt reaction is not involved, and have proposed the triazoline (367) as a reasonable intermediate. They have also shown that in certain cases rearrangement coupled with desulphurization provides a completely regioselective method for conversion of 2-cycloalkenones to the ene lactams (368). 

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