Chirality multiplication

Chiral multiple-coupling reagents have been prepared in enantiomerically pure form by enantio-selective saponification of diesters of meso-2-nitrocyclohexane-l,3-diols (Eq. 3.44) with pig liver esterase (PLE).69... 

Asymmetric catalysis, shown by equation 5 is an ideal method for synthesizing optically active compounds (2,3). The chemical approach, which uses a small amount of a chiral man-made catalyst, produces naturally occurring and nonnaturally occurring chiral materials in large quantities. The efficiency of chirality multiplication, defined as [(major enantiomer - minor enantiomer)/chiral source], can be infinite for asymmetric catalysis. Recent advances in this area are turning chemists dreams into reality at both academic and industrial levels. 

Chirality amplification, 11,255 catalytic reactions, 289 DAIB complexes, 273 mechanism, 275 organozinc chemistry, 273 Chirality multiplication, 2... 

Another substrate class for reductive radical cyclisation reactions, which was studied in our laboratories, are 4-(4 -iodoalkyl)quinolones (e.g. 27 Scheme 10). High enantioselectivities could be achieved even at 0 °C (up to 99% ee) or at ambient temperature (up to 96% ee). Furthermore, an unexpected chirality multiplication was observed with low catalyst loadings (Dressel and Bach 2006). 4-(4/-Iodobutyl)quinolone (27) can be synthesised from4-methylquinolonein three steps by alkylation with 3-/< /7-butyldimcthylsilyl(TBDMS)oxy-l-iodopropane, deprotection of the alcohol and iodo-dehydroxylation in an overall yield of 31%. 

Dressel M, Bach T (2006) Chirality multiplication and efficient chirality transfer in exo- and endo-radical cyclisation reactions of 4-(4 -iodobutyl)quinol-ones. Org Lett 8 3145-3147... 

In an idealistic sense, a chemical approach which uses a small amount of a chiral catalyst to produce either enantiomer, cleanly and efficiently from a prochiral precursor, is the preferred method. For such asymmetric catalysis the efficiency of chiral multiplication can be infinite. The use of chiral metal complexes as homogeneous catalysts has become one of the most powerful economically and environmentally sound strategies for the preparation of enantiopure compounds. An excellent comprehensive review of asymmetric catalysis in organic synthesis has recently been published by Noyori [30]. 

The key steps in this process are catalytic and with a reputed overall chiral multiplication efficiency in excess of 400 000 for the asymmetric step, the environmental impact of this process must be extremely low. 

Noyori has achieved the asymmetric catalytic isomerization of allylic amines to optically active enamines using his Rh -BINAP complex (see Chap. 14). This reaction, isomerization of geranyldiethylamine to ( )-enamine of (/f)-citronellal, is used in Japan as a key step in the synthesis of 1500 tons per year of (-)menthol starting from myrcene. The catalyst is recycled, which still increases its efficiency, and the total chiral multiplication reaches 400,000 mol product per mol catalyst. The optical purity of citronellal obtained (96-99%) is far larger than that of natural citronellal (82%). ... 

Ranganathan, D. and Kurur, S. Synthesis of totally chiral, multiple armed, poly glu and poly asp scaffoldings on bifunctional adamantane core. Tetrahedron Lett 1997, 38 1265-1268. 

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