Hydroxy amides rearrangement

When an a-hydroxy amide is treated with Br2 in aqueous NaOH under Hofmann rearrangement conditions, loss of C02 occurs and a chain-shortened aldehyde is formed. Propose a mechanism. 

Activated A-alkyl-O-acylhydroxamic acid derivatives 75 undergo base catalysed rearrangement to give 2-acyloxyamides 76 in good to excellent yields (50-100%) (equation 26). These precursors of 2-hydroxy amides (77) are good intermediates to prepare ethanol-amines, oxindoles and oxazolidinediones. 

Strongly acidic conditions gives the amino alcohol. However, the reaction can be stopped at an intermediate stage if it is carried out under mild conditions. For example, the initially formed amino ester can be isolated or trapped in certain cases although it is more commonly rearranged to the hydroxy amide, typically under mildly basic conditions (Schemes 8.88 and 8.89). The configuration of the oxazoline at the 4 and 5-positions is normally retained under the hydrolysis... 

Details of the oxidation and rearrangement of tabersonine (126) to (+)-14,15-dehydrovincamine (127) and (+)-14,15-dehydro-16-cp/-vincamine (128), which were previously recorded only in the patent literature, have now been published.90 A minor product in this sequence of reactions was formulated as (129), since hydrogenation, hydrolysis, and decarboxylation afford a hydroxy-amide (130), which can be reduced to rhazinilam (131) (Scheme 18). The reaction of 14,15-dehydrovincamine (127) with iodine and potassium iodate results in the formation of a dehydro-derivative (not isolated), followed by closure of the tetrahydrofuran ring. The product is the iodo-compound (132), which, as an iodo-enamine, loses its iodine when treated with acid, with formation of the alkaloid criocerine (133).90... 

Hofmann rearrangement (the mechanism is shown in Section 24.6) of an a-hydroxy amide produces a carbinolamine intermediate that expels ammonia to give an aldehyde. 

On the route to benzo[c]phenanthridine alkaloids [37], naphthol 51 (Scheme 20) was 0-alkylated with 2-bromo-2-methylpropionoamide under forcing conditions to give 52 in 93% yield. The rearrangement of 52 was executed with sodium hydride in DMF-DMPU and the hydroxy-amide 53 was hydrolyzed to give the aminonaphthyl derivative 54. 

Aimnoethyl)indoles have been prepared from 3-hydroxy-2-methoxyindolines by way of a Claisen o-amide rearrangement. 0-Acylhydroxamic acid derivatives (82) have been found to undergo a base-catalysed rearrangement to give secondary... 

Hydroxy-amides. - Wittig rearrangement of acetamide (424) [LDA, -85 C] provides almost exclusively the erythro-a-hydroxy-amide (425). The likely transition-state geometry suggests that the presence of vinylic substituents larger than methyl should at least maintain this level of selectivity during rearrangement. Unfortunately similar reactions of chiral amides derived from prolinol result in only moderate asymmetric induction. 

Phosphate-derived a-oxycarbanions can rearrange into a-hydroxy phosphonates. This class of rearrangement is known to proceed with retention of configuration at the carban-ion terminus. The enantioselective version of this rearrangement has been developed using a chiral lithium amide as a base (equation 115) . The reaction of benzyl dimethyl phosphate 182 with amide R,R)-63 in THF gave the hydroxy phosphonate (5 )-183 in 30% in enantioenriched form (52% ee). 

The Beckmann rearrangement of ketoximes with triphenylphosphine and iV-chloro-succinimide occurs at room temperature almost instantaneously and their corresponding secondary amides are obtained in high yields (equation 83). The triphenylphosphine 271 is activated by the iV-chlorosuccinimide 270 affording the salt 272, which is attacked by the iV-hydroxy group of the oxime 217 forming the intermediate 273. 

Hammerschmidt, F. Hanninger, A. Enantioselective deproto nation of benzyl phosphates by homochiral lithium amide bases. Configurational stability of benzyl carbanions with a dialkoxyphosphoryloxy substituent and their rearrangement to optically active a-hydroxy phosphonates. Chem. Ber. 1995, 328, 823-830. Avolio, S. Malan, C. Marek, I. Knochel, P. Preparation and reactions of functionalized magnesium carbenoids. Synlett 1999, 1820-1822. 

The lithium amides 98, prepared from 4-hydroxy—lactone and imines, rearranges in the presence of lithium chloride at low temperature to form -lactams 99 (Scheme 52) with cholesterol absorption inhibition properties <1999JOC3714, CHEC-III(2.01.3.10.10)69>. 

---