Regioselective Photochemical Rearrangement of N‐Mesyloxylactams

Abstract

N‐Mesyloxylactams can undergo ring contraction either by C‐3 (usually observed) or C‐5 migration. C‐5 migration can occur when the C‐3 migration product possesses ring strain, but it does not usually compete with C‐3 migration. The greater preference for C‐3 migration is due to the carbonyl oxygen atom, which greatly stabilizes the intermediate.

Photochemical and Thermal Ring-Contraction of Cyclic Hydroxamic Acid Derivatives

“…So far, we have not been able to develop a general and satisfactory oxidation method to convert lactams to hydroxamic acids . Cyclic hydroxamic acid derivatives 3 can be prepared by amidation (Scheme , 7 → 3i ), cyclization ( 8 → 3b ) or Mitsunobu reactions ( 10 → 3c ) . Such methods are unsuitable to make N -chlorolactams.…”

“…In earlier work, we have compared the photochemical rearrangement of N -mesyloxylactams 2 with that of N -chlorolactams 1 . Invariably, the former leads to higher yields of products than the latter upon irradiation at 254 nm (Scheme ).…”

“…We have recently reported on the photochemical rearrangement of N -chlorolactams and N -mesyloxylactams, currently the only methods able to effect such migration on secondary amides . Since these reports, we have developed a thermal rearrangement of cyclic hydroxamic acids (Scheme ), which not only complements the current photochemical methods but also gives an unprecedented level of control over the regiochemical outcome of the ring-contraction event for certain substrates.…”

A Photorearrangement To Construct the ABDE Tetracyclic Core of Palau’amine

“…The yield of 83% is remarkable, given the introduction of such severe strain in the structure: the difference in strain energy between trans- bicyclo­[4.3.0]­nonane and trans bicyclo­[3.3.0]­octane amounts to 44 kJ/mol. , The developing strain actually does not seem to influence the yield of the product at all, as it is comparable or even superior to other rearrangements performed on unstrained substrates. It even compares favorably to some substrates with fully substituted (quaternary) migrating centers, which usually rearrange in higher yields than their lesser substituted analogs. , N -Mesyloxylactam 37b , obtained from the minor diastereomer 36b , rearranged with equal ease to give a similar mixture of 38b and 39b in comparable yield (81%).…”

“…We had previously demonstrated our rearrangement’s potential to generate a trans -cyclopenta­[ b ]­pyrrolidine (Scheme ). The yield of 29 was only 16%, but this product was totally unexpected, and we knew that it could be improved. Herein, we report an efficient synthesis of the ABDE tetracyclic carbon framework of palau’amine using this strategy.…”