Diastereoselection reactions

Asymmetric synthesis is a method for direct synthesis of optically active amino acids and finding efficient catalysts is a great target for researchers. Many exceUent reviews have been pubHshed (72). Asymmetric syntheses are classified as either enantioselective or diastereoselective reactions. Asymmetric hydrogenation has been appHed for practical manufacturing of l-DOPA and t-phenylalanine, but conventional methods have not been exceeded because of the short life of catalysts. An example of an enantio selective reaction, asymmetric hydrogenation of a-acetamidoacryHc acid derivatives, eg, Z-2-acetamidocinnamic acid [55065-02-6] (6), is shown below and in Table 4 (73). 

Brefeldin A, an antiviral agent which impedes protein transport from the endoplasmic reticulum to the Golgi complex, was synthesized as the racemate using a number of interesting diastereoselective reactions. 

I.3.3.3.3.2.2. Simple Diastereoselection Reactions of Racemic -Substituted Allylboron Reagents with Achiral Aldehydes and Ketones... 

Even if the organometallic compound is racemic, it still may be possible to get a diastereoselective reaction that is, one pair of enantiomers is formed in greater amount than the other. 

The use of additives such as germanium can lead to highly diastereoselective reactions." Using chiral auxiliaries or chiral additives, good enantioselec-tivity can be achieved. 

Ziegler and Saprong described a stoichiometric cyclization onto an alkyne for the synthesis of the carbocyclic core of entecavir from diacetone glucose. Inverse addition was required to minimize deoxygenation. The highly diastereoselective reaction is tolerant to silylethers [101]. 

A number of P-chirogenic diaminophosphine oxides (DIAPHOXs) 275 derived from aspartic acid were prepared via hydrolysis of triaminophosphine intermediate 274, generated in a fully diastereoselective reaction of triamines 273 with phosphorus trichloride (Scheme 65) [102, 103],... 

The palladium-catalyzed oxidation of the 1,2-divinylcyclohexane system was applied to diastereoselective reactions with the use of chiral acids as nucleophiles25. With this technique an asymmetric induction of up to 76% was obtained in the formation of 21 from 14 (equation 9). The use of molecular sieves was essential in order to obtain a good asymmetric induction. 

The synthesis of optically active compounds by the diastereoselective reaction of allyltitanium reagents with chiral electrophiles has also been reported. The reaction of allyltitanium reagents with chiral imines proceeds with excellent diastereoselectivity, as shown in Eq. 9.28, thus providing a new method for synthesizing optically active homoallylic amines with or without a P-substituent [51,52],... 

Ring opening of the recently synthesized imidazooxaphosphinine 88 was experienced to occur in the presence of alcohols <1996TL977, 1998NN939>. Diastereoselective reaction took place in dichloromethane solution between 2 and 30 min depending on the alcohol used to yield the triester 89. 

Indolizidine alkaloids. The key step in a new stereocontrolled synthesis of these alkaloids, such as castanospermine (5), depends upon the diastereoselective reaction of an azagluco aldehyde with allylmetal reagents catalyzed by Lewis acids (12, 21-22). Thus reaction of allyltrimethylsilane with the aldehyde 1 and TiCL, (excess) in CH2C12 at - 85° results in the product 2, formed by selective chelation of the ot-amino aldehydo group with TiCl4. The product can be converted into 5... 

Asymmetric lactonization.1 The diamide 3, prepared from (R)-l and 2, on treatment with TFA is converted into the 8-lactone 4 in 98% de by a highly diastereoselective reaction with the pro-S-carbonyl group of 3. 

Diastereoselective reaction with fl-alkoxy-a-methylpropionaldehydes.1 The reaction of (R,R)-1 with the chiral aldehyde 2a provides the syn-homoallylic alcohol... 

The corresponding crotylboronates, (R,R)- and (S,S)-5 also undergo highly diastereoselective reactions with the same chiral aldehydes, and again the diaster-... 

Mary of the molecules with biological activity contain more than two asymmetric centers and the synthesis of these occurs via a diastereoselective reaction. 

What are the main parameters influencing the diastereoselective reactions ... 

Diastereoselective reactions, where one or more chiral centres are generated in a selective manner within a molecule that already contains chirality, to produce single diastereoi-somers (epimers) are very common in nature. Some examples of chemical processes which harness the properties of biocatalysts are shown below. 

From the data available it is clear that diastereoselective reactions of type (1) are very useful for control over absolute stereochemistry, but they require stoichiometric amounts of the chiral auxiliary. Reactions of type (3), on the other hand, have so far... 

Singlet oxygen affords a variety of regio and diastereoselective reactions with chiral allylic alcohols amines - (e.g. substrate 161, Scheme 58) and chiral cyclohexadienes - that are useful for synthetic transformations. For example, the photooxygenation of a chiral allylic alcohol was used recently as the key step in the total syntheses of plakorin 162 and ewawfio-chondrilin (Scheme 58). If the photooxidation... 

New chiral auxiliaries for nucleophilic reactions have been prepared from 5-hydroxy-l-tetralone <2001TA2605> and myrtenal <2001TA3095> and their use in diastereoselective reactions has been evaluated. It was found that both the tetralone- <2003EJ0337, 2003JOC6619> and the myrtenal- <2003TA3225, 2005TA1837> derived 2-acyl-l,3-oxathianes reacted diastereoselectively with nucleophiles (Equations 60 and 61). 

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