Tandem carbonyl ylide formation

The rhodium-catalyzed tandem carbonyl ylide formation/l,3-dipolar cycloaddition is an exciting new area that has evolved during the past 3 years and high se-lectivities of >90% ee was obtained for both intra- and intermolecular reactions with low loadings of the chiral catalyst. 

Directed Syntheses with Tandem Carbonyl Ylide Formation/[l,3]-Dipolar Cycloaddition... 

Enandoselective tandem carbonyl ylide formation-cycloaddition of a-diazo- -keto esters is achieved in hexane with [Rh2(5-DOSP)4] (1 mol %) at room temperature to give the corresponding cycloadducts with moderate enantioselectivity [73] (Eq. 8A.49). 

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>. 

The reaction of diazo compounds 717 with a C=0 or C=N bond produces the carbonyl or azomethine ylides 718, which undergo subsequent hetero-[3 + 2]-cycloaddition reaction, giving the five-membered heterocyclic compounds 719 (Scheme 2 2 3).297298 Hodgson et al. reported a concise, stereoselective synthesis of cis-nemorensic acid via the tandem carbonyl ylide formation-cycloaddition.2971 The reaction of the di-azodione 720 with propargyl bromide in the presence... 

The enormous potential of this tandem carbonyl ylide formation-1,3-dipolar cycloaddition strategy has further been applied in the total synthesis of structurally complex polygalolides A and B (125,126). The synthesis illustrates the power of this methodology for rapid assembly of the unusual dioxatricyclic ring system 124 around the core oxabicyclo[3.2.1]octanone (Scheme 38). Thus, the first total synthesis of polygalolides A and B (125,126)... 

They also reported high levels of enantioselection for the inter-molecular cycloadditions of ester-derived carbonyl ylides with DMAD (up to 93% ee, Rh2(S-PTTL)4) (Scheme 7.22) [58] and a-diazo ketone-derived carbonyl ylides with aromatic aldehydes (up to 92% ee, Rh2(S-BTPV)4) (Scheme 7.21) [59]. Dirhodium (II) tetrakis[A -tetrachIorophthaIoyI-(S)-ferf-Ieucinate], Rh2( 5-TCPTTL)4, was found to be an exceptionally effective catalyst for tandem carbonyl ylide formation/cycloaddition reactions of... 

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. 

The use of diazocarbonyl compounds in the synthesis of O-bridged systems is the approach of choice. There are a few main synthetic strategies of bridged framework building based on this approach tandem cyclization with carbonyl ylide formation/cycloaddition, tandem cyclization with 0x0-nium ylide formation/sigmatropic shift, intramolecular cyclopropanation, and cyclization with single bond insertion. 

Over the last 15 years, Padwa et al. (73,74) have been heavily involved with the study and application of carbonyl ylides as cycloaddition precursors in synthesis. Their work has helped make the tandem ylide formation-dipolar cycloaddition process a synthetically accessible transformation. Much of Padwa s early work focused on determining the extent and limitations of this methodology. Many of the early systems were carbocyclic in nature and helped define basic parameters such as... 

Friedrichsen and co-workers (133) approached substituted benzotropolones from an aromatic substituted carbonyl ylide with a tethered alkyne as the intramolecular dipolarophUe (Scheme 4.67). Starting from an aromatic anhydride, Friedrichsen was able to make the tethered alkyne via addition of either pentyn-ol or hexyn-ol, then transform the recovered benzoic acid to the a-diazocarbonyl cycloaddition precursor. Addition of rhodium acetate resulted in the tandem formation of cyclic carbonyl ylide followed by cycloaddition of the tethered alkyne producing the tricyclic constrained ether 252. Addition of BF3 OEt2 opened the ether bridge, forming the benzotropylium ion, which subsequently rearranged to form the tricyclic benzotropolone (253). 

The tandem cyclization-cycloaddition reaction of 1-diazoacetyl-7,7-dimethylbicyclo[2.2.1]heptan-2-one (1) with dimethyl butynedioate catalyzed by rhodium(II) acetate dimer in benzene at 25 °C, afforded a formal [3 + 2] cycloadduct 2 in 85% yield with complete diastereofacial selectivity48. This reaction is interpreted to proceed via rhodium carbenoids and subsequent transannular cyclization of the electrophilic carbon onto the adjacent oxo group to generate a cyclic carbonyl ylide. followed by 1,3-dipolar cycloaddition. Similar reactions are observed with other dipolar-ophiles, such as propargylic esters and A -phenylmaleimide. Studies dealing with the geometric requirements of dipole formation were undertaken. 

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