Cycloaddition reactions carbon-heteroatom double bonds

The only successful [2 + 2] cycloaddition reported so far involving an MCP derivative and a carbon-heteroatom double bond is the reaction of BCP (3) with chlorosulfonylisocyanate (CSI) (594) [13b, 143], CSI is a typical [2 + 2] cycloaddend with most alkenes, but has been demonstrated to be also involved in stepwise cycloadditions via polar intermediates [157], The reaction of BCP and CSI gives the [2 + 2] cycloadduct 596 only as a minor product, besides the major [3 + 2] adduct 599 (Scheme 83) [13b, 143], Therefore, it has been reasonably suggested that both products derive from a common dipolar intermediate 595, formed by nucleophilic attack of BCP on the electron-deficient carbon of CSI (Scheme 83) [13b]. 

Photochemical or thermal extrusion of molecular nitrogen from ot-diazocarbonyl compounds generates a-carbonylcarbenes. These transient species possess a resonance contribution from a 1,3-dipolar (303, Scheme 8.74) or 1,3-diradical form, depending on their spin state. The three-atom moiety has been trapped in a [3 + 2] cycloaddition fashion, but this reaction is rare because of the predominance of a fast rearrangement of the ketocarbene into a ketene intermediate. There are a steadily increasing number of transition metal catalyzed reactions of diazocarbonyl compounds with carbon-carbon and carbon-heteroatom double bonds, that, instead of affording three-membered rings, furnish hve-membered heterocycles which... 

Besides carbon — carbon multiple bonds, carbon —heteroatom double bonds (C = 0 C = NR) are also capable of undergoing metal-catalyzed [3 4- 2] cycloadditions. However, the simplest class of substrates, i.e. ketones and imines, respectively, could so far only be employed when 2-(trimethylsilylmethyl)prop-2-enyl acetate (1) was used as a TMM synthon. These reactions, which additionally require the presence of cocatalysts such as tin or indium compounds when ketones are used as substrates, lead to the selective formation of 3-methylenetetrahydrofurans and 3-methylenepyrrolidines (3, X = O, N), respectively. ... 

Carbon-heteroatom double bonds can also participate in this reaction. These include both carbonyl compounds (Scheme 11.37) and imines (Scheme 11.38). Addition to aldehydes is co-catalysed by tin(II) or indium(III) salts. Under these conditions, tetrahydrofiirans are obtained. The presence or absence of the co-catalyst can also switch the reaction from one mode to another (Scheme 11.39). An indium cocatalysed cycloaddition to a 7-pyrone aldehyde 11.117 was used in a synthesis of aureothin 11.122 and A-acetylaureothamine 11.123 (Scheme 11.40). Cross-metathesis of the exo-cyc ic alkene 11.118 allowed a subsequent Suzuki coupling with a gem-dibromide 11.120 that showed the expected selectivity (Section 2.1.4.2). This reaction required the use of thallium ethoxide as the Lewis base to suppress the formation of side products. A Negishi coupling completed the synthesis of aureothin 11.122. Reduction and acylation of the nitro group yielded A-acetylaureothamine 11.123. The latter compound is active digainst Helicobacter pylori, a bacterium behind stomach ulcers. 

The scope of this cycloaddition reaction was very promising. Subsequently, removal of the CC-double bond and stereoselective functionalizations at positions 4 and 5 (carbohydrate numbering) was investigated for the synthesis of carbohydrates and related natural products, to provide C-3 branched carbohydrate derivatives (or C-4 heteroatom substituted derivatives after carbon/he-teroatom exchange reactions). However, the desired hydrogenation of such systems with various hydrogen donors has mainly resulted in low yields and/or side reactions due to the inherent stability of the formal CC-double bond (12., 15). ... 

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