Asymmetric transformations agents

The DKR processes for secondary alcohols and primary amines can be slightly modified for applications in the asymmetric transformations of ketones, enol esters, and ketoximes. The key point here is that racemization catalysts used in the DKR can also catalyze the hydrogenation of ketones, enol esters, and ketoximes. Thus, the DKR procedures need a reducing agent as additional additive to enable asymmetric transformations. 

Troger s base, the resolution of which with a strongly acidic resolving agent is accompanied by a crystallization-induced asymmetric transformation (also see p426)87. 

The structurally novel antimitotic agent curacin A (1) was prepared with an overall yield of 2.5 % for the longest linear synthesis. Three of the four stereogenic centers were built up using asymmetric transformations one was derived from a chiral pool substrate. Key steps of the total synthesis are a hydrozirconation - transmetalation protocol, the stereoselective formation of the acyclic triene segment via enol triflate chemistry and another hydrozirconation followed by an isocyanide insertion. For the preparation of the heterocyclic moiety of curacin A (1) the oxazoline - thiazoline conversion provides efficient access to the sensitive marine natural product. 

Crystallization-induced asymmetric transformation has already been described by Leuchs in 1913 during the resolution of 2-(2-carboxybenzyl)-l-indanone with brucine.34 In this case spontaneous racemization occurred. More recently researchers at Sanofi observed spontaneous racemization during the resolution of 3-cyano-3-(3,4-dichlorophenyl)propionic acid (7), most likely as a result of the basic resolving agent [>-(-)-N-1 n etli y I g I near nine [d-(-)-MGA] (8) (Scheme 7.6).35 The enantiopure cyano acid, obtained in 91% overall yield, is subsequently reduced to (+)-4-amino-3-(3,4-dichlorophenyl)-l-butanol (9), a key intermediate in the phase 2 synthesis of tachykinin antagonists. 

The high-yield synthesis of the racemate via a Strecker synthesis is elegantly combined with the asymmetric transformation process. Addition of the resolving agent (S)-mandelic acid results in the formation of both diastereoisomeric salts. In the presence of benzaldehyde these salts are in equilibrium with the Schiff base, which racemizes readily. The low solubility of the diastereoisomeric salts (in apolar solvents) eventually allows obtainment of a >95% yield of the (/f) (.S )-salt in more than 99% diastereoisomeric excess. After decomposition of this salt by hydrochloric acid, pure (Ah-phenylglycine amide is obtained, and the resolving agent can be recycled. 

Strategy A. The enamine strategy to asymmetric transformations of carbonyl compounds is also exploited for the construction of carbon-heteroatom bonds using proline as catalyst, dissolved in ionic liquid media. Thus, a highly enantioselective a-aminoxylation of aldehydes and ketones has been reported based on the use of nitrosobenzene as the aminoxylating agent and catalysed by proline in [bmim] and [pmim] [BF4] and The reaction reported in Figure 6 affords poorer values in terms of yield and reaction rate when carried out in molecular solvents. Conversely, proline dissolved in the IL is recovered up to 6 times without appreciable loss of activity. 

Wilen. S.H. Qi, J.Z. Williard, P.G. Resolution, asymmetric transformation, and configuration of Troger s base. Application of Troger s base as a chiral solvating agent. J. Org. Chem. 1991, 56, 485-487. 

Chloro-bridged dipalladium(ii) resolving agents R,R)- and (dinuclear metal complex as the corresponding mono-solvate in a typical second-order asymmetric transformation. 

The interest of our group in the systematics of the reactivity of organic solids has led us in recent years to the investigation and exploitation of reactions in chiral crystals for the performance of asymmetric syntheses [1,2]. In classical asymmetric transformations [3, 4] there is always the necessity of the presence of an outside chiral agent e.g. a chiral catalyst or chiral handle ). On the other hand, in the asymmetric syntheses of the type we are investigating the induction is applied by the chiral environment which the crystal itself provides at the reaction site. 

Meanwhile, if synthesized in vitro, complementary RNA forms secondary double helices (Geiduschek et aL, 1962). Later work in the same laboratory (Geiduschek et al., 1964) showed that RNA synthesis in vitro (on DNA templates) is symmetrical (i.e., it copies both DNA strands) if the DNA is partially degraded. If the DNA molecules are intact, RNA synthesis is asymmetrical, i.e., in this case only one strand acts as template. This evidently accounts for the results obtained by Bresler and co-workers (1964), who obtained artificial double-helical DNA hybrids, introduced them intoB. cells as transforming agent, and found that both... 

The use of chiral auxiliaries to impart dissymmetry has become a powerful tool for controlling the stereochemical outcome of chemical transformations. Many of these auxiliaries have been drawn from the chiral pool of natural materials. While high levels of asymmetric induction have been achieved in many cases, none of these natural products has emerged as a general agent, in part because typically only one enantiomer of the auxiliary is readily available. 

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