Methylene migration

Schmidt reactions with sodium azide and strong acids, if they occur through tetrahedral reaction intermediates, lead primarily to nitrogen insertion adjacent to methylene rather than methine groups. There are no really satisfactory reasons for preferential methylene migration in this case [81]. 

The ketenimine (93) reacts only at the C=N bond to give pyrroles and pyrrolines with methylene migration (equations 102,103). Carbon (hoxide codimerizes smoothly with methylenecyclopropanes to yield lactones with alkene isomerization (equations 104, lOS). The Pd -catalyzed rearrangement of y-butyrolactone (94) to butenolide (95) indicates that this CO2 insertion reaction is reversible. Hiis is fur-ter supported by the observation that lactone (94) can serve as a TMM precursor in the codimerization with aldehydes and electron-deficient alkenes (equations 106, 107). No cycloaddition to ketenes or simple ketone carbonyls has ever been reported. 

In a less complex rearrangement, Coates and Chen (66) found that acetolysis of longicamphenilyl tosylate (104) affords, in addition to nor-longicyclene (105) and acetate products, the novel tricyclic olefins (106) and (107). The rearrangement pathway from (104) to (106) is pictured as a C-3 to C-4 hydride shift, followed by methylene migration and then proton elimination. In formic acid, (106) goes over to (107). 

You et al. reported the iridium-catalyzed enantioselective functionalization of indoles and pyrroles. In the event, indole 181 is transformed, via an intramolecular allylic alkylation, into a spirocyclic intermediate at C3, which then undergoes selective methylene migration to form 182 with no loss of enantiopurity (up to 99% ee is obtained).The indole ring can tolerate substitution with various halogens or methoxy groups, while pyrroles can be substituted with alkyl or aryl groups (13JA8169). 

Megestrol acetate (79) is stmcturaHy related to progesterone (1). It has been prepared from medroxyprogesterone acetate (74) by chloranil-mediated dehydrogenation. It also has been prepared from hydroxyprogesterone acetate (42) via 6-methylenation and double-bond migration (109,110). 

In the alternative approach.the 1,3-dipolar system can be constructed in several ways. Treatment of a-chloroacylhydrazones of diaryl ketones and certain aralkyl and dialkyl ketones (382) with NaH in anhydrous THF gives l-(disubstituted methylene)-3-oxo-l,2-diazetidinium inner salts (383). Reaction of (383) with DMAD in methylene chloride gave (384), a 2 1 adduct with loss of CO. Double bond migration in (384) occurred on heating to give (385). The intermediate in the cycloaddition was found to be (386), which on heating lost CO to form a new ylide system which in turn underwent reaction with more DMAD <81JA7743). 

A common consequence of migration in complex molecules is that tetrasubstituted olefins result, which can be hydrogenated only with difficulty, if at all. It is easier to try to prevent hindered olefin formation than it is to correct it. Attempted hydrogenation of the exocyclic methylene group in 15 proved difficult when using an aged 10% Pd-on-C catalyst there was a... 

Purinergic signalling is also concerned with longterm events, such as cell proliferation, migration, differentiation and death associated with development and regeneration [1, 3, 4]. For example, a,(3-methylene ATP produces proliferation of glial cells, whereas adenosine inhibits proliferation. A p2y8 receptor was... 

Finally, it is worthwhile to note that the methylene-transfer pathway does not involve direct transfer of a CH2 group. An H atom migration pathway is a more accurate description of this pathway, given the experimental and theoretical evidence. 

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