Enantioselectivity, carbene synthesis

These complexes can be isolated in some cases in others they are generated in situ from appropriate precursers, of which diazo compounds are among the most important. These compounds, including CH2N2 and others, react with metals or metal salts (copper, palladium, and rhodium are most commonly used) to give the carbene complexes that add CRR to double bonds.1063 Optically active complexes have been used for enantioselective cyclopropane synthesis.1064... 

Enantioselective carbene transfer to olefins is an important area of asymmetric synthesis [134,155-157]. Recent growth in the area of transition metal porphyrin chemistry has, in part, been driven by the increased interest associated with metal-catalyzed cyclopropanation, in particular with rhodiiun porphyrins [158-166]. 

Suzuki and Takikawa [99] developed an enantioselective carbene-catalyzed cross-benzoin reaction for the synthesis of (+)-sappanone B (266) (Scheme 17.46). Compared with the catalysts introduced by Rovis and co-workers [100], Suzuki and co-workers optimized and identified triazolium salt 264 by introducing electron-withdrawing substituents (two CF3 group) to improve the reactivity and enantiose-lectivity. The key cross-benzoin reaction commenced with benzaldehyde derivative 263 in the presence of triazolium salt 264 and the base Et3N to afford 265 (92%, 95% ee), which was subsequently converted into (+)-sappanone B (266). 

Synthesis of aziridines by treatment of carbenes with imines was reported by Jacobsen [56]. A metallocarbene 104 derived from ethyl diazoacetate and copper fluorophosphate was treated with N-arylaldimines to form aziridines with reasonable diastereoselectivities (>10 1 in favor of cis) but with low enantioselectivities (about 44% ee). This was shown to result from a competitive achiral reaction path-... 

The potential of Fischer carbene complexes in the construction of complex structures from simple starting materials is nicely reflected in the next example. Thus, the reaction of alkenylcarbene complexes of chromium and tungsten with cyclopentanone and cyclohexanone enamines allows the di-astereo- and enantioselective synthesis of functionalised bicyclo[3.2.1]octane and bicyclo[3.3.1]nonane derivatives [12] (Scheme 44). The mechanism of this transformation is initiated by a 1,4-addition of the C -enamine to the alkenylcarbene complex. Further 1,2-addition of the of the newly formed enamine to the carbene carbon leads to a metalate intermediate which can... 

Zhang YR, He L, Wu X, Shao PL, Ye S (2008) Chiral N-heterocyclic carbene catalyzed Staudinger reaction of ketenes with imines highly enantioselective synthesis of W-Boc P-lactams. Org Lett 10 277-280... 

Chapter 10 considers the role of reactive intermediates—carbocations, carbenes, and radicals—in synthesis. The carbocation reactions covered include the carbonyl-ene reaction, polyolefin cyclization, and carbocation rearrangements. In the carbene section, addition (cyclopropanation) and insertion reactions are emphasized. Recent development of catalysts that provide both selectivity and enantioselectivity are discussed, and both intermolecular and intramolecular (cyclization) addition reactions of radicals are dealt with. The use of atom transfer steps and tandem sequences in synthesis is also illustrated. 

In the context of our work in the area of chiral nucleophilic carbenes and their utility in organic synthesis, we have developed a conceptually distinct approach to catalyzed acylation using a-haloaldehydes as acylation precursors. The use of a chiral triazolium salt in the presence of base allows an enantioselective desymme-trization of meio-hydrobenzoin to proceed in 83% ee and good yield ... 

So what is left to be accomplished During the current decade one can expect further asymmetric applications and catalyst designs for metathesis reactions, a maturing of chiral catalyst development for cyclopropanation and insertion with increasing synthetic applications, and decreased reliance on traditional Fischer carbenes in synthesis. Major changes remain for ylide applications, especially those that can be enantioselective, in catalytic carbene chemistry, and advances in nitrene chemistry that are comparable to those achieved over the years in carbene chemistry are in their infancy. 

Fig. 4 and Table 4 summarize some other reaction types and also some very special cases of enantioselection. Quartz catalysts (Ml) have been used for dehydration (45) and isomerization (44) reactions (again with very low ee) and Cu-tartrate (M6) catalyzes the carbene addition 43 with an acceptable optical yield, giving an intermediate in a steroid synthesis [49]. 

Di(carbene)gold(I) salts, oxidation, 2, 293—294 Dicarbido clusters, with decarutheniums, 6, 1036 Dicarbollide amides, with tantalum, 5, 184 Dicarbollide thorium complexes, synthesis and characterization, 4, 224—225 Dicarbollyl ligands, in nickel complexes, 8, 185 Dicarbonyl complexes arylation with lead triacetates diastereoselectivity, 9, 389 enantioselectivity, 9, 391 mechanisms, 9, 387 reaction examples, 9, 382 indium-mediated allylation, 9, 675 with iridium, 7, 287 reductive cyclization, 10, 529 in Ru and Os half-sandwiches, 6, 508 with Zr—Hf(II), 4, 700... 

The intramolecular diene-carbene cycloaddition equivalence and an enantioselective Birch reduction-alkylation by the chiral auxiliary approach. Total synthesis of ( )- and (—)-longi-folene. Journal of Organic Chemistry,... 

He M, Bode JW (2005) Catalytic synthesis of y-lactams via direct annulations of enals and N-sulfonylimines. Qrg Lett 7 3131-3134 He M, Struble JR, Bode JW (2006) Highly enantioselective azadiene Diels-Alder reactions catalyzed by chiral N-heterocyclic carbenes. J Am Chem Soc 128 8418-8420... 

With respect to the application of asymmetric carbene catalysis as a tool for enantioselective synthesis, the last decade s major success is based on substantial improvements in catalyst development. Early reports dealt with implementing chirality in thiazolium scaffolds (Sheehan and Hunneman 1966 Sheehan and Hara 1974 Dvorak and Rawal 1998), but their catalytic performance suffered from either low yields or low ee-values. In this regard, the investigation of triazole heterocycles as an alternative core structure (Enders et al. 1995) has played a crucial role to provide heterazolium precatalysts improving both asymmetric benzoin and Stetter reactions. An intramolecular Stetter reaction yielding chromanones upon cyclization of salicylaldehyde-derived substrates is commonly used as a benchmark reaction to compare catalyst efficiency (Scheme 1 Ciganek 1995 Enders et al. 1996 Kerr et al. 2002 Kerr and Rovis 2004). 

In conclusion, it is obvious that A-heterocyclic carbenes and their unique, but concurrently versatile reactivity have already proven wide applicability. The offered catalytic (and enantioselective) access to important reactive intermediates such as homoenolates or enolates as well as their additional catalytic properties will smooth the way for mild and sustainable synthesis of multifunctionalized compounds. 

---