Beckmann rearrangements regioselectivity

Regioselective Beckmann rearrangements were used as key steps in the synthesis of phosphonoalkyl azepinones (Scheme 36) [43b] and in a formal total synthesis of the protein kinase C inhibitor balanol (Scheme 37) the optically active azide 197 derived from cyclohexadiene mono-oxide was converted into ketone 198 in several steps. After preparation of the oxime tosylates 199 (2.3 1 mixture), a Lewis acid mediated regioselective Beckmann rearrangement gave the lactams 200 and 201 in 66% and 9% yield, respectively. Lactam 201 underwent a 3-e im-ination to give additional 200, which served as a key intermediate in a balanol precursor synthesis (Scheme 37) [43 cj. 

Beckmann rearrangement of the oxime from 3-phosphonoalkylcyclohexenones 401 afforded lactams and regioselective migration of the non-unsaturated substituent was observed (equation 164). 

Multi-dimensional NMR was also the tool in the structure elucidation of dihydroazocine 10 in order to prove the addition regioselectivity <2003JOC1447>, and in the synthesis of various benzazocines via Beckmann rearrangement <2006TL4721>. 

The reductive Beckmann rearrangement of oximes has been effected with several types of aluminum hydride reagents. Early examples exhibited only moderate regioselectivity, giving mixtures of primary amines and rearranged secondary amines. Recently, diisobutylaluminum hydride was reported to be most satisfactory for this type of transformation (equation 20). Here dichloromethane is the solvent of choice, and attempted use of ethereal solvents results in the formation of a mixture of primary and secondary amines. ... 

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. 

Rearrangements. Cyclic ketones utM sdroxyalkyl azides." Regioselectivity is d Beckmann rearrangement of ketoxime o emperature. 

Rearrangements. Cyclic ketones undergo ring expansion on reaction with hydroxyalkyl azides." Regioselectivity is dependent on steric and electronic factors. Beckmann rearrangement of ketoxime carbonates has been observed at room temperature. 

While the factor that controlled the regioselectivity of the photo-Beckmann rearrangement of steroidal a,P-unsaturated oximes remains obscure, the different regioselectivity in the lactam formation may originate from a stereoelectronic effect — the relative geometry between a lone pair on the nitrogen and the migrating CC bond in the oxaziridine intermediate. 

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>. 

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