Aldehydes carbonyl ylides

Interaction of a carbonyl group with an electrophilic metal carbene would be expected to lead to a carbonyl ylide. In fact, such compounds have been isolated in recent years 14) the strategy comprises intramolecular generation of a carbonyl ylide whose substituent pattern guarantees efficient stabilization of the dipolar electronic structure. The highly reactive 1,3-dipolar species are usually characterized by [3 + 2] cycloaddition to alkynes and activated alkenes. Furthermore, cycloaddition to ketones and aldehydes has been reported for l-methoxy-2-benzopyrylium-4-olate 286, which was generated by Cu(acac)2-catalyzed decomposition of o-methoxycarbonyl-m-diazoacetophenone 285 2681... 

Phosphoniutn ylides can be generated by treatment of diazoacetates and triphe-nylphosphine or triethyl phosphite with catalytic amounts of RuCl2(PPh3)2 [ 1343] or ReOCl3(PPh3)2 [1344]. If these reactions are conducted in the presence of aldehydes, carbonyl olefination takes place in high yields. 

The formation of carbonyl ylides from esters was also observed by a laser photolysis study conducted by Chateauneuf and Liu (6). The formation of ester ylides is much less common than from aldehydes or ketones (Scheme 4.4). 

Epoxide 96 was prepared such that photolytic conversion to the carbonyl ylide could be followed by an intramolecular cycloaddition with the tethered pendant olefin. However, photolysis of epoxide 96 led only to the formation of the regio-isomer 97 and the aldehyde 98 with no evidence of the corresponding cycloadduct. It was presumed that 97 arose from the ylide by thermal recyclization to the epoxide while 98 could form through the loss of a carbene from the ylide. The failure of the tethered alkene to undergo cycloaddition may have resulted from a poor trajectory for the cycloaddition. An extended analogue (99) allowed greater flexibility for the dipolarophile to adopt any number of conformations. Photolysis of epoxide 99 did lead to formation of the macrocyclic adduct 100, albeit in modest yields. 

Although there are fewer examples of aldehydes serving in the formation of carbonyl ylides, there have been several reports regarding their generation. Maas... 

Wenkert and Khatuya (51) examined the competition between direct insertion of a carbene into furan (via cyclopropanation) and ylide formation with reactive side-chain functionality such as esters, aldehydes, and acetals. They demonstrated the ease of formation of aldehyde derived carbonyl ylides (Scheme 4.30) as opposed to reaction with the electron-rich olefin of the furan. Treatment of 3-furfural (136) with ethyl diazoacetate (EDA) and rhodium acetate led to formation of ylide 137, followed by trapping with a second molecule of furfural to give the acetal 138 as an equal mixture of isomers at the acetal hydrogen position. 

Reactions of the same carbonyl ylide intermediate with aldehydes are even more fruitful. The Rh2(OAc)2 catalyzed reaction proceeds at room temperature in the presence of 2 mol% of the catalyst, but the diastereoselectivity is disappointingly low (endo/exo = 49 51, Scheme 11.56). However, when 10 mol% of the cocatalyst Yb(OTf)3 is added, the reaction becomes highly exo-selective (endo/ exo = 3 97) (198). Suga has extended this Lewis acid catalyzed carbonyl ylide cycloaddition reaction to catalyzed asymmetric versions. The chiral cocatalyst employed is ytterbium(III) tris(5)-1,1 -binaphthyl-2,2 -diyl phosphonate, Yb[(S) BNP]3 (10 mol%). In the reaction of methyl o-(diazoacetyl)benzoate with benzyloxyacetaldehyde in the presence of Rh2(OAc)2 (2 mol%) at room temperature with the chiral Yb catalyst, the diastereoselectivity is low (endo/exo = 57 43) and the enantiopurity of the endo-cycloadduct is 52% ee. 

The carbonyl ylide generated from metal carbene can also add to C=0 or C=N bonds. The [2 + 3]-cycloaddition of carbonyl ylide with G=0 bond has been used by Hodgson and co-workers in their study toward the synthesis of zaragozic acid as shown in Scheme n 27a,27d Recently, a three-component reaction approach to syn-a-hydroxy-f3-amino ester based on the trapping of the carbonyl ylide by imine has been reported.The reaction of carbonyl ylide with aldehyde or ketone generally gives l,3-dioxolanes. Hu and co-workers have reported a remarkable chemoselective Rh2(OAc)4-catalyzed reaction of phenyl diazoacetate with a mixture of electron-rich and electron-deficient aryl aldehydes. The Rh(ii) carbene intermediate reacts selectively with electron-rich aldehyde 95 to give a carbonyl ylide, which was chemospecifically trapped by the electron-deficient aldehyde 96 to afford 1,3-dioxolane in a one-pot reaction (Equation (12)). 

Photolysis of ene oxiranes not possessing an a-cyano group has also led to intramolecular carbonyl ylide cycloaddition, but in low yield.123 Thus, bicyclic tetrahydrofuran (223) was formed in 35% yield by photolytic disrotatory opening of the corresponding franr-diphenyloxirane. Thermolytic conrotatory opening of the isomeric m-oxirane also afforded tetrahydrofuran (223) in 25% yield accompanied by an aldehyde byproduct. 

Efforts to trap the carbonyl ylide intermediate by intramolecular [3 + 2] cycloaddition to a C=C bond were unsuccessful. Rather, the decomposition of allyl (trimethylsilyl)diazoacetate (218) (equation 69) in the presence of aldehydes gave 1,3-dioxolan-4-oncs 219 their formation has been explained by 1,5-cyclization of the carbonyl ylide intermediate followed by a Claisen rearrangement122. With acetone as carbonyl component, the reaction proceeds analogously. Clean formation of 219 occurred only with Rh2(OOCC3F7)4 as catalyst, while the copper triflate catalyzed version led to a mixture of 219, an oxirane and the product of intramolecular carbenoid... 

Dilithio-1,3-dienes were found to react with aldehydes to form polysubstituted 2,5-dihydrofurans in a regio- and stereoselective manner <02OL2269>. Like other metal-carbene reactions, rhodium-catalyzed tandem carbonyl ylide formation - cycloaddition with propargyl bromide gave the 2,5-dihydrofuran in good yield <020L1809>. 

Dondoni A, Marra A, Merino P (1994) Installation of the pyruvate unit in gly-cidic aldehydes via a Wittig olefination-Michael addition sequence utilizing a thiazole-armed carbonyl ylide. A new stereoselective route to 3-deoxy-2-ulosonic acids and the total synthesis of DAH, KDN, and 4-epi-KDN. J Am ChemSoc 116 3324... 

Various other [3 + 2] cycloadditions, affording chiral, anellated C6o derivatives with stereogenic centers in the addends are reported in literature. The products were generally obtained as racemates and resulted from reaction of buckminsterfullerene with species like 2,3-disubstituted 2//-azirincs (via nitrile ylides [under direct irradiation] or via 2-azaallenyl radical cations [sensitization by photoinduced electron transfer]),365 1-substituted 5-diazopentane-1,4-diones (via cyclic carbonyl ylides),366 7-alkylidene-2,3-diazabicyclo[2.2.1] hept-2-ene (via a diradicaloid trimethylenemethane derivative),367 1-benzylpy-razolidine-3-ones in the presence of aldehydes (via pyrazolidinium ylides),368 2-trifluoromethyl-2,5-dihydro-l,3-oxazol-5-ones (via nitrile ylides),369 nitro-alkanes in the presence of triethylamine and trimethylsilyl chloride (via N-silyloxynitrones),370 or dv-HOCH2 CH=C H C H 2 OCO 2 H( in the presence of... 

Difluorocarbene converts aldehydes and ketones into ge/n-difluoroalkanes 1 (Table 5). The proposed mechanism involves formation of a carbonyl ylide, which gives the difluoro compound by loss of carbon monoxide. 

Carbonyl ylides, often generated from a carbene and an aldehyde or ketone, are in general reactive intermediates that can isomerize to stable products (oxiranes, enolethers) or can be tn ped by [3+2] cycloaddition reactions [18]. As Scheme 8 shows, silyldiazoacetic esters can also be used to generate carbonyl ylides [19]. 

Dioxolanone 33 is obtained when the unsaturated silyldiazoester 30 is decomposed by Rh2(pfb)4 in the presence of an aldehyde or of acetone (Scheme 11) [21]. The reaction sequence is likely to include formation and (probably reversible) 1,5-cyclization of carbonyl ylide 31, and Cope rearrangement of the allylvinylether 32. In analogy to carbonyl ylide 21, the SiMe3 should occupy the exo-position in 31, thereby bringing the ester carbonyl in a geometry that is favorable to the cyclization step. Again, the choice of catalyst determines the product pattern, since CuOTf catalysis affords not only 33, but also oxirane 22 and the intramolecular cyclopropanation product 34. 

Further studies on a-diazo ketones with a second more remote carbonyl group have appeared and formation of a carbonyl ylide and its addition to an added aldehyde yields bicyclic dioxolanes 199 (Scheme 19) <2004TL6485, 2005ARK(xi)146>. A rearrangement is clearly involved in the more complex reaction of a silyl diazo ester to give a dioxolan-4-one (Equation 66) <20020L4631>. 

Other approaches to the key carbonyl ylide intermediates are also effective and Sml2 treatment of an a-iodo silyl ether in the presence of an aldehyde also gives the dioxolane product (Equation 78) <1996JA3533>. Similarly, desilylation of 219 gave an intermediate that added to carbonyl compounds to give dioxolanes and to thioketones to give oxathiolanes (Scheme 21) <1996SL234>. 

---