RESUMO
There is a need for the preparation of enantiomerically pure compounds for various applications. An efficient approach to achieve this goal is asymmetric catalysis. The chiral catalyst is usually prepared from a chiral auxiliary, which itself is derived from a natural product or by resolution of a racemic precursor. The use of non-enantiopure chiral auxiliaries in asymmetric catalysis seems unattractive to preparative chemists, since the anticipated enantiomeric excess (ee) of the reaction product should be proportional to the ee value of the chiral auxiliary (linearity). In fact, some deviation from linearity may arise. Such nonlinear effects can be rich in mechanistic information and can be synthetically useful (asymmetric amplification). This Review documents the advances made during the last decade in the use of nonlinear effects in the area of organometallic and organic catalysis.
Assuntos
Dinâmica não Linear , Catálise , Ligantes , Compostos Organometálicos/química , Solubilidade , EstereoisomerismoRESUMO
A strong asymmetric amplification is observed in the addition of diethylzinc on aromatic aldehydes in the presence of the bistriflamide of trans-1,2-diaminocyclohexane 3a. The asymmetric amplification originates from the insolubility of the catalyst precursor 3a of low enantiomeric excess (ee), with a concomitant large increase of ee for the minor soluble part of 3a. Controlled mono-N-acetylation of 3a (20% ee) at -78 degrees C allowed isolation of 4 possessing 90% ee. [reaction: see text].
Assuntos
Aldeídos/química , Cicloexilaminas/química , Compostos Organometálicos/química , Álcoois/síntese química , Álcoois/química , Catálise , Estrutura Molecular , EstereoisomerismoRESUMO
A novel HIV protease inhibitor was designed using a morpholine core as the aspartate binding group. Analysis of the crystal structure of the initial lead bound to HIV protease enabled optimization of enzyme potency and antiviral activity. This afforded a series of potent orally bioavailable inhibitors of which MK-8718 was identified as a compound with a favorable overall profile.
RESUMO
A novel reaction involving tandem construction of C-N and C-C bonds via the simultaneous Ritter and Houben-Hoesch reactions on Baylis-Hillman adducts leading to a convenient, one-pot synthesis of 2-benzazepine derivatives is described. A facile stereoselective transformation of the Baylis-Hillman adducts into (E)- and (Z)-allyl amides is also presented.
RESUMO
The reaction of a racemic reagent on a mixture of enantiomers with small ee (ee=enantiomeric excess) has been studied for amine acylation. A substantial asymmetric amplification could be realized, for example, from 67 to >95.5 ee. The combination of asymmetric amplifications is subsequently discussed. Two sequential asymmetric amplifications, one using a racemic reagent and another using a positive nonlinear effect allowed us to start from 1.5 % ee and end with a large amount of a product of 97 % ee.