Intramolecular stereoselective carbene additions

Rearrangements to a carbene site or intramolecular insertion or addition reactions by a carbene may be stereoselective. The distribution... 

The generation of carbenes by the thermolysis of lithium or sodium salts of tosyl-hydrazones continues to provide interesting chemistry. The selectivity exhibited by 7-bicyclo[2,2,l]hept-2-enylidene (generated from the corresponding tosylhydrazone) is quite the opposite to that expected from theoretical predictions and earlier studies. Addition to 3,3-dimethylbut-l-ene affords the syn-isomer (118) as the major adduct and consequently any carbene-7i interaction resulting in bridge bending cannot of itself dominate the stereoselectivity of addition. Furthermore, the intramolecular insertion products of 2-methylbicyclo[2,2,l]hept-2-en-7-ylidene have been characterized and, from the product ratios, the species behaves as a true carbene. A 3-furyl-... 

Tandem intramolecular 1,3-dipolar cycloadditions and cycloreversion, phosphinimine alkylidenemalonate cyclization, and retro-malonate additions have been reviewed.52 The origins of the stereoselection in the 1,3-dipolar cycloadditions to chiral alkenes53 and the 3 + 2-cycloadditions of fullerene, Cea, have been reviewed.54 The selectivity of the double 3 + 2-cycloaddition of tethered double vinyl carbene species in die presence of C6o varies witii the nature of the tether.55... 

In 2012, Alexakis and co orkers disclosed the first stereoselective annulation reaction between ynals and a-cyano-l,4-diketones which is mediated by a catalytic amount of a triazolium salt precatalyst and a weak carboxylate base. This transformation proceeds smoothly under mild reaction conditions and generates three contiguous stereogenic centers, one of which is a quaternary acetal carbon, and affords privileged bicyclic scaffolds in 61-90% yields with up to 20 1 diastereomeric preference. A mechanistic rationalization for the NHC-catalyzed annulation of a-cyano-l,4-diketones with ynals is proposed as the following. Initially, the free carbene condenses with a molecule of ynal to form the key d,p-unsaturated acylazolium intermediate followed by a direct nucleophilic conjugate addition of 1,4-diketone. Subsequent intramolecular H-migration and an irreversible lactonization furnish the observed bicyclic product and liberate free carbene for the next catalytic cycle (Scheme 7.98). 

Intramolecular addition processes involving latent carbenes have been reported twice. On one hand, the thermolysis of 2,2-dialkoxy-5,5-dimethyl-A -l,3,4-oxadiazolines (38) as latent carbenes formed bicyclic compounds (39) via an efficient and highly stereoselective formal 4- -1-cycloaddition process, carbene (40) being postulated as the key intermediate. On the other hand, the deprotonated carbenic forms of alkyne-tethered imidazolium (41) and 1,2,4-triazolium salts (42) have been found to undergo 6-exo-dig intramolecular addition, leading to zwitterionic intermediates (43) and (44) that rearrange to give 2-substituted imidazole (45) and bicyclic 1,2,4-triazole (46), respectively. ... 

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