Carbenoids ylide generation

As the reactive substrates become more complex, a number of alternative carbenoid pathways are able to compete effectively with ylide generation. It has been shown that the judicious choice of a catalyst (46,47) can have a remarkable effect on the reaction pathway (Scheme 4.29). 

Addition of a rhodium carbenoid to an alkyne leads to a cyclopropene derivative. In an intramolecular context, the fused cyclopropene moiety is unstable and undergoes ring opening to generate a rhodium vinyl carbenoid entity, which can then undergo cyclopropanation or cyclopropena-tion, carbon hydrogen insertion, and ylide generation. This is illustrated... 

Tandem carbonyl ylide generation from the reaction of metallo carbenoids with carbonyl continues to be of great interest both mechanistically and synthetically. Effective carbonyl ylide formation in transition metal catalyzed reactions of diazo compounds depends on the catalyst, the diazo species, the nature of the interacting carbonyl group and competition with other processes. The many structurally diverse and highly successful examples of tetrahydrofuran formation cited in this mini-review clearly indicate that the tandem cyclization/cycloaddition cascade of metallo carbenoids has evolved as an important strategy in both carbo- and heterocyclic synthesis. 

Other reactions. /3-Lactams, such as 182, were prepared in moderate to good yields by [2,3]-rearrangement of ammonium ylides produced by the reaction of copper carbenoids tethered to allylic amines (Scheme 77) <2001J(P1)3312>. The catalyst of choice in the generation of carbenoid/ylide from a-diazoketone precursor is copper(n) acetylacetonate. 

The generation of sulfonium yhdes relies mostly on three strategies (Scheme 78). The classic variant uses sulfide alkylation to the sulfonium salts 316 which can be deprotonated to dehver the desired yhdes 317 [180,181]. A related method involves silane 320 as the alkylating agent to allow for regioselective ylide generation via fluoride ion induced desilylation [182]. Finally, the action of carbenes 319 or metal-bound carbenoids offers a direct means for ylide generation [183,184]. 

Sulfonium Ylides Generated via Carbene or Carbenoid Precursors. 72... 

Allenic sulfides (37) have been obtained with moderate to good enantio-selectivities (up to 81%) in sigmatropic rearrangements of sulfonium ylides generated from propargyl aryl sulfide (35) and aryldiazoacetates (36) as carbenoid source catalyzed by chiral Rh(ll) (38a,b) and Cu(l) (38c) catalysts [34] (Scheme 8). 

Bis(sulfonyl)carbene (carbenoid) is generated photolytically, thermally or catalytically from bis(sulfonyl)diazomethane or from the corresponding phenyliodonium ylide (Houben-Weyl, Vol. E19b, ppl735, 1739-1743). In the latter case only, the carbene reacts with an alkene to form l,l-bis(sulfonyl)cyclopropanes (Houben-Weyl, Vol. E19b, pl743). 

Ylide generation from diazo compounds by reaction of carbenoids is a better method than photochemical or thermal dediazoniation in the presence of organic substrates containing heteroatoms, because these dediazoniations without metal catalysis yield, in most cases, not very selective carbenes. Here again, the copper-catalyzed route is in most cases inferior to that with rhodium catalysts. The diazoketo ester with a terminal thioalkyl group (8.145) can be obtained from the... 

The catalytic effectiveness of ruthenium porphyrins for ylide generation in reactions of ethyl diazo acetate and diisopropyl diazomethylphosphonate with some allylic substrates was described for the first time by Simoimeaux and coworkers (Scheme 20) [194]. These reactions result in products of the [2,3]-sigmatropic rearrangement of intermediate allylic ylides. It was demonstrated that simple ruthenium porphyrins are highly effective catalysts for carbenoid reactions with alkyl allyl sulfides and alkyl allyl amines providing... 

Rainer has studied the sulfonium ylide-mediated thio-Claisen rearrangement. Rhodium carbenoid 443, generated from rhodium acetate and alkenyl diazoacetate 441, reacted with the 2-ethylthioindole 440 to reveal the sulphur ylide 445. Proton shift generated the ketene aminethio acetal 446 which underwent thio-Claisen rearrangement to yield indoline 442 in excellent yield. 

The aza-[2,3]-Wittig rearrangement of a vinylaziridine-derived quaternary azir-idinium ylide (i.e., [2,3]-Stevens rearrangement) has recently been reported (Scheme 2.53) [86], The aziridinium ylide 219, generated by the intramolecular reaction of a copper carbenoid tethered to a vinylaziridine, underwent a [2,3]-Ste-vens rearrangement to furnish the bicydic amine 220 with the indolizidine skeleton. 

Ammonium ylides can also be generated by the carbenoid route. 

Allylic ethers and acetals can react with carbenoid reagents to generate oxonium ylides that undergo [2,3]-sigmatropic shifts.224... 

Interaction of an electrophilic carbene or carbenoid with R—S—R compounds often results in the formation of sulfonium ylides. If the carbene substituents are suited to effectively stabilize a negative charge, these ylides are likely to be isolable otherwiese, their intermediary occurence may become evident from products of further transformation. Ando 152 b) has given an informative review on sulfonium ylide chemistry, including their formation by photochemical or copper-catalyzed decomposition of diazocarbonyl compounds. More recent examples, including the generation and reactions of ylides obtained by metal-catalyzed decomposition of diazo compounds in the presence of thiophenes (Sect. 4.2), allyl sulfides and allyl dithioketals (Sect. 2.3.4) have already been presented. 

The sulfonium ylide derived chemistry of penicillins continues to meet the interest of several research groups. It is well known that intermolecular carbenoid attack at the sulfur atom generates a sulfonium ylide which undergoes spontaneous opening of the thiazolidine ring to furnish a l,2-sm>-penicillin 326). Novel examples of this reaction type were found upon Rb2(0Ac)4-catalyzed decomposition of diazomalonic esters in the presence of various penicillins this transformation constituted the opening step of a synthetic sequence directed towards 2-alkoxycarbonyl-cephems 345 a) or modified penicillins 345 b). Similar to its reaction with 4-thio-2-azetidinone... 

C6 and C9 are at opposite ends of a four-carbon unit, but since one of these atoms (C7) is saturated and quaternary, a Diels-Alder reaction is unlikely (can t make diene). The combination of a diazo compound with Rh(II) generates a carbenoid at C9. The nucleophile 06 can add to the empty orbital at C9, generating the 06-C9 bond and a carbonyl ylide at C6-06-C9. Carbonyl ylides are 1,3-dipoles (negative charge on C9, formal positive charge on 06, electron deficiency at C6), so a 1,3-dipolar cycloaddition can now occur to join C2 to C6 and Cl to C9, giving the product. Note how a relatively simple tricyclic starting material is transformed into a complex hexacyclic product in just one step ... 

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