Mechanistic investigations, asymmetric

The discussion of the catalytic, asymmetric variants will incorporate a significant emphasis on the interplay of mechanistic investigations and synthetic optimization studies to provide a unified picture of the cyclopropanation methods. Finally, recent insights provided by computational analysis of the transition structures for cyclopropanation will be discussed. 

Structural and Mechanistic Investigations in Asymmetric Copper(I) and Copper(II) Catalyzed Reactions... 

As mentioned earlier, it was originally assumed that this reaction is mechanistically related to the copper-catalyzed diazo-transfer cyclopropanation. As such, the intervention of a metal complexed nitrenoid intermediate has been theorized as the principal mode of action. Mechanistic investigations in this reaction have paralleled the development of the asymmetric version and hence, will be discussed in concert. 

In this review, we focus mainly on the preparative utility of organic peroxides, and only few mechanistic investigations are discussed. This review covers synthetic methodologies for the preparation of alkyl hydroperoxides and dialkyl peroxides (Section II) and the synthetic use of these peroxides in organic chemistry (Section III). In Section II, general methods for the synthesis of organic hydroperoxides and dialkyl peroxides are discussed, as well as the preparation of enantiomerically pure chiral hydroperoxides. The latter have attracted considerable interest for asymmetric oxidation reactions during the last years. 

The present review covers chiral lithium amides in asymmetric synthesis and related mechanistic investigations. The extensive work on use of achiral lithium amides in synthesis... 

For recent mechanistic investigations into the selectivity of the Sharpless asymmetric epoxidation see P. G. Potvin and S. Bianchet, J. Org. Chem., 1992, 57, 6629. 

Lohray, B. B., Bhushan, V., Reddy, G. J., Reddy, A. S. Mechanistic investigation of asymmetric aminohydroxylation of alkenes. Indian J. Chem., Sect. S2002, 41B, 161-168. 

Non-linear effects were discovered in 1986 [5]. They are now widely recognized in many catalytic reactions, and provide a useful tool for mechanistic investigations. Moreover, they can have some practical applications. For example, in the case of asymmetric amplification it is not necessary to perform a costly complete resolution of a chiral ligand if the reaction involves a strong (-i-)-NLE. The concept of non-linearity has been extended to mixtures of diastereomeric ligands (vide supra). Finally, asymmetric amplification is very useful in reactions which display asymmetric autocatalysis, giving high levels of enantioselectivity after initiation with a catalyst of very low ee. 

Rhodium(II) complexes, e.g.. Rh2(OAc)4, are the mildest and most efficient and versatile catalysts for cyclopropanation, especially with diazo carbonyl reagents5 la 1 31 8S. Side reactions are C-H-insertion and Wolff rearrangement. Intensive mechanistic investigations and a comparison with other metal catalysts have been described10 2. Rhodium catalysts have frequently been used in stereoselective and asymmetric cyclopropanation12. 

Based on their mechanistic investigation on the Cu -mediated oxidative coupling of 2-naphthol derivatives, Smrcina, Kocovsky, and co-workers were able to develop the first catalytic asymmetric oxidative biaryl coupling reaction (Scheme 3.3). AgCl was used as the stoichiometric oxidant to regenerate the Cu species. In order to avoid the formation of detrimental HCl by-product, the corresponding sodium 2-naphthol salts were employed as the coupling partners. The desired product 3 was obtained in 41% yield (8 turnovers) with 32% ee. 

In 2011, Sasai and co-workers developed an asymmetric oxidative cyeliza-tion of 4-alkenoic acids in good yields and moderate ees (Scheme 5.16). The utilization of the spiro bis(isoxazoline) ligand (M,5,5)- Pr-SPRIX was crucial for this asymmetric transformation. Preliminary mechanistic investigation showed that a [(n-allyl)Pd] intermediate was involved in the reaction. This represents the first example of enantioselective oxidation of allylic C—H bonds by using only a chiral palladium catalyst. 

Ashimori, A., Bachand, B., Caller, M.A. et al. (1998) Catalytic asymmetric synthesis of quaternary carbon centers. Exploratory studies of intramolecular Heckreactions of (Z)-a,/S-unsaturated anilides and mechanistic investigations of asymmetric Heck reactions proceeding via neutral intermediates. J. Am. Chem. Soc., 120, 6488-99. 

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