Cascade reactions ylide formation

Hodgson and co-workers have studied the intramolecular cascade carbonyl ylide formation-cycloaddition with chiral Rh(ii) catalysts.After screening a series of chiral Rh(ii) catalysts, high enantioselectivity was achieved in the reaction of 98 by using the Rh(ii) catalyst with binaphthyl phosphate-derived chiral ligands dirhodium(ii) tetrakis[(i )-6,6 -didodecylbinaphtholphosphate] [Rh2(i -DDBNP)4] (Equation (13)). 

In the dipole cascade reaction, a proton must be removed from the a-carbon atom in order to generate the azomethine ylide. When the a-position of the pyrrolidine ring was blocked by a benzyl group, formation of the azomethine ylide dipole could not occur. In fact, treatment of diazoketone 186 with rhodium(II) acetate in the presence of dimethyl acetylenedicarboxylate afforded only the carbonyl ylide-derived cycloadduct 187 in 95% yield [117]. 

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. 

There are also cases where addition of thiyi radicals to unsaturated carbon-carbon bonds is the crucial step for thiophene ring formation. Flash vacuum pyrolysis (FVP) of the phosphorus ylide 90 affords initially the alkyne 91, which produces thiyi radical with loss of methyl radical. Cyclization of the resulting radical affords thienothiophene 92 as the final product with loss of one more methyl radical (Scheme 20) <1995SL53>. FVP of ylide 93 results in a multistep cascade reaction leading to 7-(2-benzothienyl)benzofuran 94 (Scheme 21) <2001SL228>. 

Reaction conditions have been developed for a metallonitrene-initiated alkyne oxidation cascade with intermolecular cascade termination by ylide formation/[2,3] Wittig rearrangement upon reaction of alkyne 245 with enantioenriched allyl ethers 246 to provide heterocyclized AT-sulfonyl imine products 247 efEciendy (13AGE5836). 

Very recently, Toda and Terada reported an elegant example of a cascade reaction by combining Rh catalysis and chiral phosphoric acid catalysis [60]. The reaction comprised a Rh-catalyzed yUde formation through an Rh-carbene intermediate and chiral phorphoric acid-catalyzed asymmetric reduction of a Hantzsch ester toward the newly formed oxonium (Schane 9.63), affording chiral building blocks 194 with satisfactory results. For the first time, this chemistry showed the trapping of oxonium ylide with reductants in asymmetric synthesis. 

The formation of the heterocycle 1 from the xylylene-bis-phosphonium salt 2 and PCI3 proceeds via a detectable intermediate 3 in a cascade of condensation reactions that is terminated by spontaneous heterolysis of the last remaining P-Cl bond in a cyclic bis-ylide-substituted chlorophosphine formed (Scheme 1) [15]. The reaction scheme is applicable to an arsenic analogue of 1 [15] and to bis-phosphonio-benzophospholides with different triaryl-, aryl-alkyl- and aryl-vinyl-phosphonio groups [16, 18, 19], but failed for trialkylphosphonio-substituted cations here, insufficient acidity prohibited obviously quantitative deprotonation of the phosphonium salts, and only mixtures of products with unreacted starting materials were obtained [19]. The cations were isolated as chloride or bromide salts, but conversion of the anions by complexation with Lewis-acids or metathesis was easily feasible [16, 18, 19] and even salts with organometallic anions ([Co(CO)4] , [CpM(CO)3] (M=Mo, W) were accessible [20]. 

The Rh(II)-catalyzed reaction of pyridone 96 with DMAD was also found to give cycloadducts derived from an intermediate azomethine ylide. The initial reaction involves generation of the expected carbonyl ylide by intramolecular cyclization of the keto carbenoid onto the oxygen atom of the amide group. A subsequent proton shift generates the thermodynamically more stable azomethine ylide, which is trapped by DMAD. This is an example of subsequent formation of ylides of two types, a phenomenon termed a dipole cascade (93JOC1144). 

The transition metal-catalyzed decomposition of a-cabonyl diazo compounds is a very important synthetic method, as has been reviewed [98]. Cu and Rh catalytic systems have been proved very effective for this process. From the perspective of synthetic and process chemists, such metal carbenes can undergo three major types of reactions cyclopropanation with alkenes, addition to an unsaturated C—C bond, and the formation of ylide, which have been the source of fruitful cascades. 

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