Ring expansion ylides

Pyrrolidone 41, obtained by literature procedures from phenylalanine, was acylated adjacent to the amide carbonyl to give 42, followed by oxidation to the dienophile 43. The ensuing cycloaddition with diene 40 afforded the funtionalized octahydroisoindole 44 in 77% yield from 41. The reaction mixture from the room-temperature Diels-Alder reaction was contaminated with small amounts of an undetermined isomeric by-product (44 by-product >15 1). The additional carbons required for the macrocyclic ring were now appended via a cleverly conceived sulfur-ylide ring expansion. 

D. Kvaskoff, P. Bednarek, L. George, K. Waich, C. Wentrup, Nitrenes, diradicals, and ylides. Ring expansion and ring opening in 2-quinazolylnitrenes, J. Org. Chem., 2006, 71,4049-4058. 

Ring expansion of activated aziridines (43) with sulfur ylides also provides a synthesis of azetidines (75JOC2990, 58BSF345, 81CC417). The highly reactive sulfonium methylide (44 R = R = H) undergoes further reaction with the azetidines (46), but the reaction is satisfactory for substituted methylides. The less reactive sulfoxonium methylide (45 R = R = H)... 

Corey s ylide (1), as the methylene transfer reagent, has been utilized in ring expansion of epoxide 75 and arizidine 77 to provide the corresponding oxetane 76 and azetidine 78, respectively. 

The reaction proceeds best when the ylide has a carbanion-stabilizing substituent. This reaction results in carbon-carbon bond formation and has found synthetic application in ring-expansion sequences for generation of medium-sized rings. 

Another Rhn-catalyzed decomposition of a a-diazoester as described by Sabe and coworkers [198] was used for the synthesis of indolizidine alkaloids (Scheme 6/2.8). It can be assumed that, first, an ammonium ylide is formed which then undergoes a 1,2-shift with ring-expansion. Thus, reaction of 6/2-40 with Rh2(OAc)4 led to a 72 28 mixture of 6/2-41 and 6/2-42 in 85 % yield. Cu(acac)2 can also be used with even better yields, but lower selectivity (65 35). 

The reaction of the same ylide 63 with dimethyl acetylenedicarboxylate (DMAD) in chloroform afforded the cyclazine 67, through aromatization of monoadduct 66 the azocine 69, which is formed through a second nucleophilic attack with ring expansion in the bis-adduct 68 and the pyrrolo derivative 71, which is formed by evolution of the bis-adduct 70 through a retro-Diels-Alder reaction (Scheme 3) <2001JOC1638>. 

The key step in the total synthesis of (—)-epilupinine 253 involved the ring expansion of a proline-derived spirocyclic ammonium ylide to give 252 through a [1,2] Stevens rearrangement, as shown in Scheme 51 <1997T16565>. 

Reduced fused azepines (e.g. 40) have been used in a new ring expansion strategy to afford fused hexahydroazoninoindoles (e.g. 41) from reaction with methyl propiolate in methanol to give the ylide intermediate A which then ring expanded via the methanol stabilised intermediate B to give 41 <06T1239>. 

The rearrangement of platinacyclobutanes to alkene complexes or ylide complexes is shown to involve an initial 1,3-hydride shift (a-elimina-tion), which may be preceded by skeletal isomerization. This isomerization can be used as a model for the bond shift mechanism of isomerization of alkanes by platinum metal, while the a-elimination also suggests a possible new mechanism for alkene polymerisation. New platinacyclobutanes with -CH2 0SC>2Me substituents undergo solvolysis with ring expansion to platinacyclopentane derivatives, the first examples of metallacyclobutane to metallacyclopentane ring expansion. The mechanism, which may also involve preliminary skeletal isomerization, has been elucidated by use of isotopic labelling and kinetic studies. 

The bismuth ylides, Ph3Bi=CHCOR, do not react with simple ketones and electron-rich olefins probably because of their relatively low electrophilic character. However, Ph3Bi=CHCOR reacts with a-keto esters [46, 67, 68], benzils [46, 67-69], orf/to-quinones [46, 67, 68], and acenaphthenequinone [70] to give epoxides, (9-arovl enolates, 3-hydroxytropones, and 3-hydroxyphenalenones, respectively, accompanied by the formation of Ph3Bi (Scheme 11). In particular, transposition and ring expansion reactions are of interest from a mechanistic point of view, since these reaction modes are unprecedented in ylide chemistry. 

Furthermore, 1,3-oxathiolanes 255 are efficiently converted, via sulfur ylide intermediates, to 1,4-oxathianes 256 and 257 by ring expansion with a silylated diazoacetate in the presence of copper catalyst (Scheme 27) <2002GC346, 2005T43>. 

Irradiation of the pyridinium dicyanomethylide (324) in benzene gives the substituted pyrrole (325), by the postulated route shown (Scheme 242) which originates from the singlet excited ylide. 7,7-Dicyanoazanorcaradiene presumably arises by N—C bond fission in the triplet which produces a dicyanocarbene (of dubious multiplicity) which is trapped by the solvent benzene (67CR(C)(264)1307). Photolysis of the imino-ylide (326) in benzene (equation 200) follows the same pathways initially but the two products result from ring expansions,... 

Asymmetric induction in the ylide formation/[l,2]-shift has also been studied with chiral metal complexes. Katsuki and co-workers examined the reaction of ( )-2-phenyloxetane with 0.5 equiv. of /< //-butyl diazoacetate in the presence of Gu(i) catalyst. With chiral bipyridine ligand 53, trans- and m-tetrahydrofurans 54 and 55 are obtained with 75% and 81% ee, respectively (Equation (6)). This asymmetric ring expansion was applied by the same group to their enantioselective synthesis of translactone. 

Besides [2,3]-sigmatropic rearrangement and [l,2]-shift reactions, the oxonium ylide may undergo other reactions. The oxonium ylide intermediate can be trapped by a protic nucleophile. Oku and co-workers have developed a method for ring expansion of cyclic ethers through oxonium ylide formation. Bicyclic oxonium ylide... 

More recently, Naidu and West have utilized a ring expansion reaction of spiro azetidinium ylide 167 in the synthesis of pyrrolizidine alkaloids. Spiro azetidinium ylide 167 is generated through a Cu(acac)2-catalyzed intramolecular reaction of a copper carbene complex with a pendant amino moiety. Subsequent [l,2]-shift gives fused bicyclic products 168 and 169 as a diastereomeric mixture. Each diastereomer was further converted to naturally occurring pyrrolizidines ( )-turneforcidine and ( )-platynecine, respectively (Scheme 18). ... 

Other synthetic routes to benzazepines involving ring expansion of six-membered heterocycles include the action of diazomethane (77CPB321), sulfonium ylides (77H(7)37> or acyl halides (75T1991) on quaternary 3,4-dihydroisoquinolines that of sulfoxonium ylides on quaternary quinolines (74IJC(B)1238) and the zinc-acetic acid reduction of quaternary 1-acyltetrahydroisoquinolines (77BSF893). Photoaddition of acyl- or aryl-nitrenes to the exocyclic alkene bond of 2-methylene-1,2-dihydroquinolines results in ring expansion to... 

---