Asymmetric Carbon-Hydrogen Insertion

Because of the synthetic interest in their products, and the potential for control of both diastereo- and enantioselectivity in their C-H insertions, catalytic reactions of cycloalkyl diazoacetates have received a great deal of attention [58-61]. For example, although cyclohexyl diazoacetate could be converted to both cis- and trans-bicychc products (Eq. 14), the abihty to control both the diastereo- and enantioselectivity proved challenging. 

McKervey, T. Ye, Modem Catalytic Methods for Organic Synthesis with Diazo Compounds, John Wiley Sons, New York, 1997. 

Doyle in Catalysis by Di- and Polynuclear Metal Cluster Complexes, R. D. Adams, 

Simonsen, V. Lynch, R. Ghosh, Reel. Trav. Chim. Pays-Bas 1995, 114, 163. 

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Doyle MP, Ratnikav M, Liu Y. Intramolecular catalytic asymmetric carbon-hydrogen insertion reactions. Synthetic advantages in total synthesis in comparison with alternative approach. Org. Biomol. Chem. 2011 9 4007-4016. 

The search for the racemic form of 15, prepared by allylic cyclopropanation of farnesyl diazoacetate 14, prompted the use of Rh2(OAc)4 for this process. But, instead of 15, addition occurred to the terminal double bond exclusively and in high yield (Eq. 6) [65]. This example initiated studies that have demonstrated the generality of the process [66-68] and its suitability for asymmetric cyclopropanation [69]. Since carbon-hydrogen insertion is in competition with addition, only the most reactive carboxamidate-ligated catalysts effect macrocyclic cyclopropanation [70] (Eq. 7), and CuPF6/bis-oxazoline 28 generally produces the highest level of enantiocontrol. 

Chiral Dirhodium(ll) Carboxamidates for Asymmetric Cyclopropanation and Carbon-Hydrogen Insertion Reactions... 

Chiral Ligands. Bidentate chelation of dirhodium(II) compounds by chiral oxazolidinones creates asymmetric sites on the metal, leading to induction in cyclopropanations and carbon-hydrogen insertion reactions. The oxazolidinones are less effective in this capacity than are the pyrrolidines. ... 

Keywords Rhodium, Carbon-Hydrogen Insertion, Cyclopropanation, Chiral, Asymmetric, Enantioselective, Intermolecular, Intramolecular, Diazocarbonyl Compounds... 

Rhodium(II)-MEPY and rhodium(II)-MACIM (methyl 1-acetylimidazolidin-2-one-4-carboxylate) complexes are efficient chiral catalysts for intramolecular carbon-hydrogen insertion reactions of diazoacetates (224) and metal carbene transformations (225). Dirhodium(II) carboxylates of similar structure (eg, piperidinonate complexes of the Rh2(ligand)4 type) have been found efficient catalysts for asymmetric cyclopropanation of olefins (226). 

For the aziridination of 1,3-dienes, copper catalysis gave better yields of A-tosyl-2-alkenyl aziridines with 1,3-cyclooctadiene, 1,4-addition occurred exclusively (50%) [46]. Good results were also obtained on rhodium catalysed decomposition of PhI=NNs (Ns = p-nitrophenylsulphonyl) with some alkenes the aziridination was stereospecific, whereas with chiral catalysts asymmetric induction (up to 73% ee) was achieved. However, cyclohexene gave predominantly (70%) a product derived from nitrene insertion into an allylic carbon-hydrogen bond [47]. 

Although the first catalysts were copper-based, the insertion of metal-associated carbenes into carbon-hydrogen bonds has undergone a renaissance with the advent of rhodium(II) carboxylate catalysts [56]. Metal-catalyzed enan-tioselective C-H insertions of carbenes have not been studied in great detail. Most of the efficient enantioselective versions of this reaction involve chiral rhodium complexes and until recently, the use of chiral catalysts derived from metals other than copper and rhodium for the asymmetric C-H insertion of metal-associated carbenes are still unexplored. 

There has been a summary of computational and experimental studies of the use of palladium complexes with A -heterocyclic carbenes (NHCs) in the asymmetric coupling of -hybridized carbon-hydrogen bonds with aryl halides. It has been shown that the electronic and catalytic properties of NHCs fused to porphyrins may be modified by varying the inner metal in the porphyrin. A DPT study of the use of palladium-NHC complexes in the asymmetric intramolecular a-arylation of 2-bromoaryl amides to give 3,3-disubstituted oxindoles (101) has been reported. The likely pathway involves insertion of the palladium into the arene-bromine bond to form a palladacycle which deprotonates to give an (9-enolate. Conversion into the C-enolate followed by reductive elimination gives the product. The intramolecular reaction of 0 a cyclopropane carbon-hydrogen bond in a 2-bromoanilide derivative has been used to form cyclopropyloxindoles, (102), in a palladium-catalysed, silver-mediated reaction. 

CAMPHOS catalyst, asymmetric hydrogenation of a,p-unsaturated carboxlic acids, 25 107-109, 112 -carbon bond, COj insertion, 28 132-134 -carbon dioxide complex, coordination, 28 125, 126, 128 oxide formation, 28 27 as catalyst, 26 335... 

When insertion of the coordinated prochiral olefin to a metal alkyl or a metal hydride takes place, the stereochemistry of the substituted carbon atom is determined as either R or S enantiomer. When the chiral alkyl group is reductively eliminated with the hydrido ligand, asymmetric hydrogenation of an olefin producing enatiomeric excess of one of the optical isomers can be achieved. 

On the basis of the fact that (R)-BMPP coordinated to the metal center can induce asymmetric addition of methyldichlorosilane across the carbon-carbon double bond of 2-substituted propenes to afford an enantiomeric excess of (R)-2-substituted propylmethyldichlorosilanes, the following processes should be involved in these reactions (a) insertion of the metal center into the silicon-hydrogen bond (oxidative addition of the hydrosilane) (b) addition of the resulting hydridometal moiety to the coordinated olefin preferentially from its re face (in a cis manner) to convert the olefin into an alkyl-metal species and (c) transfer of the silyl group from the metal center to the alkyl carbon to form the product. Since process (b) most likely involves diastereomeric transition states or intermediates, the overall asymmetric bias onto the R configuration at the chiral carbon would have already been determined prior to process (c). A schematic view of such a process is given in Scheme 1. 

Based on extensive studies of C-H transformation with Pd(ii), Yu et al. recently achieved asymmetric desymmetrization in a CDC reaction (Scheme 7.26). ° Boc-L-Isoleucine (Boc-Ile-OH) was an effective chiral ligand for the Pd(ii)-catalyzed enantioselective C-H activation of a,a-diphenylacetic acid Na salt. The resultant Pd-aryl intermediate is considered to undergo insertion into styrenes or acrylates, followed by p-hydrogen elimination to afford the coupling product with a chiral quaternary carbon center in good... 

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