Diasteroselective synthesis

The energy profiles for an enantioselective and a diasteroselective synthesis are compared in Figure 14.2. An interesting feature of the asymmetric catalytic synthesis is the nonlinear correlation between the optical purity of the chiral catalyst or auxiliary and that of the reaction product, reported... 

A few years previously, the same research group reported a one-pot condensation of three components (methylphenylglyoxylate (MPG), aniline, and aromatic aldehyde), promoted by a TiCl3/pyridine system under anhydrous conditions, for the diasteroselective synthesis of P-amino-a-hydroxyesters (Equation 14.24) [32]. 

A large amount of activity on 1,4-benzodiazepine derivatives was reported in 2004. Tetrahydro-l,4-benzazepin-2-one derivatives are of interest as P-turn peptidomimetics and their solid-phase synthesis was reported by Kim et al. <04JC0207>. The diasteroselective synthesis of two enantiopure tetrahydro-l,4-benzodiazepin-5-ones was also achieved based on intramolecular azide cycloaddition and subsequent stereoselective reduction of the 1,4-benzodiazepinone products <04TA687>. A different approach to tetrahydro-1,4-benzodiazepin-5-ones 80 involves the 1,2-thiazine 1-oxides 77 as key intermediates. These intermediates were then converted to the nitroaryl amides 78 (R , R, R = H or Me) which could be cyclised to 80 after hydrogenation of the nitro group via the intermediates 79 <04T3349>. 

SCHEME 23.26. Sanies and co-workers diasteroselective synthesis of (—)-rhazinilam. 

Vinylstannanes with hydroxy groups in the allylic position undergo enantioselective and diasteroselective hydrogenation in the presence of rhodium catalysts, as illustrated in reaction 19275. Vinylstannanes can be converted into /1-stannylacrylic esters in a two-step synthesis, as shown in reaction 20276. 

Electroenzymatic reactions are not only important in the development of ampero-metric biosensors. They can also be very valuable for organic synthesis. The enantio- and diasteroselectivity of the redox enzymes can be used effectively for the synthesis of enantiomerically pure compounds, as, for example, in the enantioselective reduction of prochiral carbonyl compounds, or in the enantio-selective, distereoselective, or enantiomer differentiating oxidation of chiral, achiral, or mes< -polyols. The introduction of hydroxy groups into aliphatic and aromatic compounds can be just as interesting. In addition, the regioselectivity of the oxidation of a certain hydroxy function in a polyol by an enzymatic oxidation can be extremely valuable, thus avoiding a sometimes complicated protection-deprotection strategy. 

Enantiopure allylic alcohols are employed widely as building blocks for asymmetric synthesis, and particularly as substrates for various diasteroselective allcene functionalization reactions such as cyclopropanation and epoxidation directed by the hydroxyl group [129]. 

This methodology opens up an efficient stereoselective access to chiral piperidi-none derivatives 60 which have opposite configuration compared to compounds 46 obtained by the tandem Mannich-Michael reaction sequence described in Section 4.3.2. The high diasteroselectivity and regioselectivity in these reactions once again illustrate the stereodifferentiating potential of carbohydrates in the synthesis of chiral heterocyclic systems. 

Asymmetric aldol reactions may also be controlled with high diasteroselectivity, but this time for the anti isomer, in reactions of A -tosyl derivatives of esters derived from 7 (eq 3). Diastereoselectivities of up to 99 1 were achieved in the illustrated titanium(IV)-mediated reaction, which has been employed for the synthesis of dipeptide isosteres for incorporation into pharmaceutical building blocks.The selectivity reverses... 

Electrochemical diasteroselective substitutions based on intramolecular asymmetric induction are highly useful for asymmetric synthesis. Recently, many studies focused on this subject have been done. 

While the majority of examples of substrate control deal with cyclic sterocontrol, there are a few examples where diasteroselectivity is induced in an acylic system.27 A notable example of this was demonstrated during the synthesis of a fragment of tubulysin, by Wipf and co-workers.28 Utilizing a Davis reagent in their synthesis of an a-hydroxy-y-amino acid, the enolate of the y-amino acid derivative 42 was reacted with 1 to form the a-hydroxy derivative 43 as a single diastereomer in good yield. The stereoselective reaction has precedence in literature and likely involves a highly chelated dianionic species.29... 

Intramolecular 1,3-DC of sugar-derived nitrones followed by reductive cleavage of the isoxazolidine N-0 bond have been used in the synthesis of aminocyclopentitols and anellated carbasugar derivatives <01TL4925, 0ITL5769, 01EJO759>. In all the reported examples the polycyclic isoxazolidines were obtained with high or complete diasteroselectivity. 

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