Ring-expansion carbonylation substrates

Altihough many of the early examples of the carbonylation of heterocycles included reactions of tetrahydrofurans, oxetanes, and azetidines, the majority of recent work has focused on the reactions of epoxides and aziridines. At this point, the ring-expansive reactions of epoxides are more general than the reactions of aziridines and occur imder milder conditions. Prior to 1994, ring-expansive carbonylation of epoxides was restricted to a few substrates. The patent by Droit and Kragtwijk s in 1994 inspired further work on these t)rpes of carbonylations, and tiiis work led to dramatic improvements in reaction scope. 

The Co-catalyzed reaction of azepane 264 n = 3) at 220 °C and 54 atm of CO gave the normal ring-expansion product 265 ( = 3) in 42% yield (Scheme 39). However, when Ru3(CO)i2 was used as co-catalyst of Co2(CO)s under the same conditions, azepanone 266 ( = 3) was obtained as the sole product in 72% yield (Scheme 39).The attempted reaction only with Ru3(CO)i2 as catalyst under the same conditions resulted in the recovery of the substrate 264 (n = 3). Thus, this unique rearrangement requires both Co and Ru catalysts. A proposed mechanism for the formation of 266 is illustrated in Scheme 40, which proposes that the origin of the lactam oxygen is the carbonyl oxygen of the A7-pivaloylmethyl group of pyrrolidine 264. ... 

Carbon attack of the carbonyl group of cyclopropyl ketones has also been achieved in dimerization reactions under McMurry and photochemical conditions. Conceivably, the reactions take place via radical anion intermediates. Photodimerization does not occur if structural features of the substrate facilitate intramolecular reactions such as ring opening, ring expansion, and ring closure. Radical... 

The introduction of a carbonyl moiety into an organic molecule using carbon monoxide requires the presence of a transition metal complex either as a catalyst or as a stoichiometric reactant. The insertion of carbon monoxide into a carbon-heteroatom bond of the heterocyclic compound comprises a simultaneous ring expansion and functionalization of a heterocyclic substrate. The carbonylation reaction provides a very convenient and effective one-step procedure for ring homologation (95ACR414). 

With the same concept, but using the more reactive Ti(III) cationic radical [Cp2TiCl(THF)2] or a cationic salphen aluminum complex in combination with the cobalt anion [Co(CO)4] , Coates et al. succeeded to make the epoxide or aziridine carbonylative ring expansion reaction catalytic (Scheme 60) [149]. For both substrates, it is proposed a nucleophilic attack of the cobalt anion at the least-substituted carbon atom of the three-membered ring, the latter being activated by the Lewis acidic part of the catalyst. Of note, catalysts 106 and 107 used in this reaction are described as ion pairs rather than M-Co bond containing complexes. 

The accepted mechanism for the carbonylation of epoxides is shown in Scheme 17.26, and the basic steps of this cycle are also thought to occur during the carbonylation of aziridines. Alper first proposed a catalytic cycle for the expansion carbonylation of aziridines by [Co(CO)J, and Coates has proposed a similar cycle for epoxide carbonylation catalyzed by complexes containing both Lewis acids and cobalt-carbonyl anions (Scheme 17.26). This mechanism consists of four steps (1) the activation of substrate by coordination to a Lewis acid (2) the S 2 attack on the substrate by [Co(CO)J (3) the insertion of CO into the new cobalt-carbon bond, and the subsequent uptake of CO and (4) ring closing with extrusion of product and regeneration of the catalytic species. 

The reaction of diazomethane with a,p-xmsaturated carbonyl compounds under classical protic conditions has been shown to produce pyrazoline products arising from 1,3-dipolar cycloaddition [3, 4]. Limited examples of a,p-xmsaturated carbonyl substrates undergoing ring expansion in the presence of Lewis acid promoters have been reported. It was not until the introduction of Lewis acids for diazoalkane ring expansion that these types of substrates were even reactive. In Drege s... 

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