Crystallization-induced diastereomer transformation

Among these amines, iso-propylamine was the most suitable for this process, because it was released from 7 during the C-C bond-forming reaction as a byproduct and was able to be reused for the CIDT without adding any additional amine. In fact, vacuum concentration of the C-C bond-forming reaction mixture left a catalytic amount of iso-propylamine in the residue, and the residual isopropylamine effectively catalyzed CIDT without the addition of further amine to afford threo-8 in 89% yield with 99% dr. The level of residual iso-propylamine was 

Entry Amine Equiv. Temp.°C Crystal Filtrate 

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Diastereoselective Slrecker reactions based on (R)-phenylglycine amide as chiral auxiliary are reported. The Strecker reaction is accompanied by an In situ crystallization-induced asymmetric transformation, whereby one diastereomer selecliveiy precipitates and can be isolated in 76-33% yield and dr > gsti. The diastereomeilcaily pure a-amino nitrtie obtained from pivaidehyde (R, = t-Bu, Rj = H) was converted in three steps to (S)-tert-leucine in 73% yieid and >98% ee. 

The observed diastereoselectivity in the asymmetric Strecker step via the crystallization-induced asymmetric transformation can be explained as shown in Figure 2. Apparently, the re face addition of CN to the intermediate imine 4 is preferred at room temperature in methanol and results in a dr 65/35. At elevated temperatures in water, the diastereomeric outcome and yield of the process are controlled by the reversible reaction of the amino nitriles 3 to the intermediate imine and by the difference in solubilities of both diastereomers under the applied conditions. . .. 

Diastereoselective Strecker reactions based on (R)-phenylglycine amide as chiral auxiliary are reported. The Strecker reaction is accompanied by an in situ crystallization-induced asymmetric transformation, whereby one diastereomer selectively precipitates and... 

Overview. To solve these problems, we present the first example of a crystallization-induced asymmetric transformation using optically pure (R)-phenylglycine amide 1 as a chiral auxiliary. The (R,S)-3 diastereomer precipitates out of solution in 76-93% yield with a diastereomeric ratio (dr) > 99/1. (106 words)... 

Our attempts to obtain a crystalline oxazolidinone were eventually successful with the (L)-iV-i-butoxycarbonyl derivatives and 4 -biphenylcarboxaldehyde, leading to 29d,[26] In solution, flie typical 85 15 equilibrium ratio of cis and trans diastereomers is observed (Table I, entry 4), When the solvent was partially removed and the residue suspended in teft-butyl methyl ether, an off-white solid precipitated, which consists of pure cw-29d in 88% yield. Analysis of the mother liquors shows very minor amounts of cis and trans product in a 85 15 ratio, along with some unreacted carbamate and a,a-dichloro biphenyl. The presence of both cis and trans isomers in the mother liquor is clear evidence that a crystallization-induced asymmetric transformation is responsible for the high selectivity. 

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