Ring expansion pyrrolidines

The reaction of methyl propiolate (82) with acyclic enamines produces acyclic dienamines (100), as was the case with dimethyl acetylenedicarboxylate, and the treatment of the pyrrolidine enamines of cycloheptanone, cyclooctanone, cycloundecanone, and cyclododecanone with methyl propiolate results in ring enlargement products (100,101). When the enamines of cyclohexanone are allowed to react with methyl propiolate, rather anomalous products are formed (100). The pyrrolidine enamine of cyclopentanone forms stable 1,2-cycloaddition adduct 83 with methyl propiolate (82). Adduct 83 rearranges to the simple alkylation product 84 upon standing at room temperature, and heating 83 to about 90° causes ring expansion to 85 (97,100). 

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. ... 

An unusual ring expansion of the pyrrolidin-2-one 305 has been reported to afford the azepine-2-thione derivative 307 on reaction with the bis silyl-substituted thioketene 304 (Equation 44) <1996CC1621>. It is probable that the... 

The dehydrochlorination of 4-(l-chloroalkyl)azetidin-2-ones with dimethyl sulfoxide offers a new route to 3,4-zfr-4-isopropenylazetidin-2-ones 369 (Equation 138) <2005JOC8717>. The reaction of the latter compounds with bromine (Scheme 53) or with a mixture of iV-bromosuccinimide and trimethylsilylazide (Equation 139) led to an electrophile-induced ring expansion toward pyrrolidin-2-ones 370 and 371. 

The chemistry of ammonium ylides formed from the reaction of cyclic amines with carbenes was found to be dependent on the ring size of the amine.52 For example, treatment of 1-benzylazetidine (104) with ethyl diazoacetate in the presence of a copper (II) catalyst afforded pyrrolidine 106 in 96% yield. This result is consistent with ammonium ylide formation followed by ring expansion. In contrast, treatment of 1 -phenethylaz-iridine (107) under identical conditions gave the fragmentation product 109 in quantitative yield. Similar results were observed for the reaction of aziridine 107 with dichlorocarbene.53 On the other hand, reaction of 1-phenethylpyrrolidine with ethyl diazoacetate in the presence of a... 

The Meisenheimer-type rearrangement of 1-substituted pyrrolidine 1-oxides 157 gives tetrahydro-2/7-l,2-oxazines 158 (Scheme 79). The -lactam 159 undergoes ring expansion to give 1,2-oxazinone 160 (Scheme 80) <2005EJ01680, CHEC-III(8.04.10)364>. 

Ring expansion of dichlorocarbene cycloadducts may be followed by further carbene cycloaddition to give 70 and 71 (R2N = morphcjJino) (Scheme 36). In the case of the pyrrolidine enamine, the reaction stops at the eniminium salt stage (69) to give structures such as 72 and 73 on hydrolysis59,60. 

Ring expansion reactions of 2-substituted pyrrolidines, with the intermediacy of a bicyclic aziridinium ion, has provided new piperidines. Treatment of the chiral olefmic imine 264 with Br2, followed by reduction of the resultant ion 265 results in the formation of a separable mixture of spiromethylpyrrolidines and a single spiropiperidine 266 (23% yield), a precursor of (-)-nitramine 267 (Scheme 80) <05SL1726>. 

Alper, RB., Meyers, C., Lerchner, A., Siegel, D.R., and Carreira, E.M., Eacile, novel methodology for the synthesis of spiro[pyrrolidin-3,3 -oxindoles] catalyzed ring expansion reactions of cyclopropanes by aldimines, Angewandte Chemie-Intemational Edition 38 (21), 3186, 1999. 

Ring expansion-carbonylation.1 The ring expansion of aziridines to /3-lactams by a Rh(l) catalyst (15,82-83) has been extended to expansion of pyrrolidines to piperidones by cobalt carbonyl-catalyzed carbonylation (equation 1). 

Ring expansion reactions of 2-substituted pyrrolidines to piperidines have been useful in certain cases, particularly in the iminosugar area. A careful analysis of the formation and fate of the condensed aziridinium ion intermediate 191 was made for the Mitsunobu reaction of 192 to maximize formation of 193 relative to simple alkylation <04SL1711> (Scheme 71). The known conversion of chiral prolinol 194 to 195 was used in the synthesis of thymine PNA monomer 196 <04BMCL2147>. 

Pyrrolidines. Pyrrolidines, via ring expansion of an activated cyclopropane ring on reaction with aldiraines, are catalyzed by magnesium iodide. Spiroannulated oxindoles are similarly obtained. 

Examples of the ring expansion of pyrrolidine derivatives to azepine derivatives include the attempted alkylation of vinylpyrrolidine (236 R = aryl) with methyl iodide to afford the tetra-hydroazepinium salt (237 R = aryl) <82AP(315)749> and thermal rearrangement of the thiono-carbonate (238) to furnish the hexahydroazepine (239) <90cpb2981>. 

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