Asymmetric synthesis catalyst controlled, examples

Shioiri and co-workers developed a catalytic asymmetric synthesis of allenes by isomerization of the alkyne 240 to allene 242 under the control of a chiral phase-transfer catalyst 241 (Scheme 4.62) [98], Although the enantiomeric excess is not high (35% ee), this is the first example of the asymmetric isomerization of alkynes under phase-transfer catalyzed conditions. 

The control of carbene reactions from diazo compounds as precursors is classically mediated by copper catalysts and all the carbene reactions discussed in Section 8 are, in fact, improved by such catalysts. Moreover, the use of ligands on the metal allows some control of the stereochemistry of the products, the most striking example being the asymmetric synthesis of cyclopropanes with an excellent optical yield (>90S ce) [35]. 

Asymmetric synthesis introduces one or more new features of chirality in a molecule. Several approaches are possible. In general, preferential formation of an enantiomer or diastereoisomer is achieved as a result of the influence of a chiral element present in the substrate, a reagent, catalyst or the environment. Chirality control is also possible in the electronically excited state,584 as demonstrated in the following examples. 

Examples of this kind of enantiomorphic or chiral selectivity are now being found in organic synthesis. Asymmetric synthesis, for example, has been demonstrated with stereo-controlled Michael addition in the synthesis of beta-lactams using chiral catalysts, where an acyl ligand such as acetyl is bound to cyclo-pentadiene carbonyl triphenylphosphine. Essentially complete enantiomorphic selectivity has been achieved in this Michael addition synthesis. Another case is enantio-morhic ketone reduction in ethylbenzene reduction in the ethylation of benzaldehyde. Using chiral catalysts, 97% selectivity has been achieved. Closely related research involves the making of catalytic antibodies and hybrid enzymes. ... 

The N-heterocyclisation of amines with alcohols represents an attractive approach to the synthesis of cyclic amines. Ir and Ru catalysts have been successfully used to form pyrrolidines, piperidines, and tetra-hydroisoquinolines. More difficult to access are piperizines and 1,2,3,4-tet-rahydroquinoxalines which require higher catalysts loadings, extended reaction times, and higher temperatures. To date, no examples exist of a catalyst controlled asymmetric N-heterocyclisation with amines and diols to produce enantiomerically enriched N-heterocycles. Still, the preparation of N-heterocycles via hydrogen borrowing offers attractive benefits no prior activation of the alcohol is required, and the only stoichiometric by-product is usually water. 

In analogy t 0 the Cu(II) complex systems, the silver(I) -catalyzed aldol reaction is also proposed to proceed smoothly through a Lewis acidic activation of carbonyl compounds. Since Ito and co-workers reported the first example of the asymmetric aldol reaction of tosylmethyl isocyanide and aldehydes in the presence of a chiral silver(I)-phosphine complex (99,100), the catalyst systems of sil-ver(I) and chiral phosphines have been applied successfully in the aldol reaction of tin enolates and aldehydes (101), Mukaiyama aldol reaction (102), and aldol reaction of alkenyl trichloroacetates and aldehydes (103). In the Ag(I)-disphosphine complex catalyzed aldol reaction, Momiyama and Yamamoto have also examined an aldol-type reaction of tin enolates and nitrosobenzene with different silver-phosphine complexes (Scheme 15). The catalytic activity and enantioselectivity of AgOTfi(f )-BINAP (2 1) complex that a metal center coordinated to one phosphine and triflate were relay on solvent effect dramatically (Scheme) (104). One catalyst system solves two problems for the synthesis of different O- and AT-nitroso aldol adducts under controlled conditions. 

The combinational use of inorganic base and chiral phase-transfer catalyst provides an efficient process for the synthesis of -hydroxyl-a-amino acids via the aldol reaction (260-262). A representative and successful example was reported by Maruoka and co-workers (319) that a highly efficient direct asymmetric aldol reaction of a glycinate Schiff base with aliphatic aldehydes has been achieved under mild organic/aqueous biphasic conditions with excellent stereochemical control activity (Scheme 67) (96 99% ee). 

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