Enantiopure amines

In a recently published report by MacMillan s group [121] on the enantioselective synthesis of pyrroloindoline and furanoindoline natural products such as (-)-flustramine B 2-219 [122], enantiopure amines 2-215 were used as organocatalysts to promote a domino Michael addition/cyclization sequence (Scheme 2.51). As substrates, the substituted tryptamine 2-214 and a, 3-unsaturated aldehydes were used. Reaction of 2-214 and acrolein in the presence of 2-215 probably leads to the intermediate 2-216, which cyclizes to give the pyrroloindole moiety 2-217 with subsequent hydrolysis of the enamine moiety and reconstitution of the imidazolid-inone catalyst. After reduction of the aldehyde functionality in 2-217 with NaBH4 the flustramine precursor 2-218 was isolated in very good 90 % ee and 78 % yield. 

The coupling of halopyridines was also extended to chiral amines. 2-Bromo-4-picoline was coupled with a series of enantiopure amines in the presence of Buchwald s palladium-BINAP catalyst system (7.71.).91... 

Research in the reviewed period 1995-2005 has covered more the chemistry of 1,3,2-dithiazoles and less the chemistry of 1,3,2-dioxazoles. 1,3,2-Oxathiazoles and their derivatives were not investigated in this period. Much attention has been paid to the neutral 1,3,2-dithiazolyl radicals including their synthesis, theoretical and structural study, and application. Special attention was given to their magnetic properties and conductivity. 1,3,2-Benzodithiazole. Y-oxidcs were of interest as enantiomeric compounds and intermediates for the preparation of enantiopure amines and alcohols. 

Enantiopure Amines by Chirality Transfer Using (/ )-Phenylglycine Amide... 

For the preparation of enantiopure amines, diastereoselective synthesis using a chiral auxiliary can be a viable approach. In this concept, in the first step a chiral intermediate is formed by reaction of a prochiral substrate with the chirality transfer agent. The key second step is a diastereoselective reaction. This is followed by cleavage of the chiral auxiliary to give the product amine. This concept is illustrated in Figure 25.1. 

In the case of the salt of a racemic acid and a racemic amine, six crystal modifications are possible (Table 5.7), while there are three crystal modifications for the salt of a racemic acid or amine with an enantiopure amine or acid (Table 5.8). If the successful enantioseparation of an amine with an enantiopure acid by diastereomeric salt formation is assumed, the diastereomers in Table 5.8 should obviously be more stable than the double salt and pseudo-diastereomer. Then, the diastereomers in Table 5.7 should be more stable than the other crystal modifications. On the other hand, this assumption leads to the conclusion that the solubilities of the diastereomers in Table 5.8 are largely different from each other. This... 

The enantioselective reduction of N acetyl enamides has a rich history and several substrate classes of N acetyl enamides can now be reliably converted to enantiopure amines (>99% ee) using rhodium based catalysts. The field has bifurcated over the past 10 years with the utility of monodentate versus bidentate ligands at the fore of the discussion. In Chapter 8, Zhou lays a strong foundation for the monodentate phosphorus ligand accomplishments and challenges. Chapter 9 provides a wonder fill complement by Zheng, who fully summarizes the bidentate phosphorus ligand literature over the past 10 years. 

Another enantiopure amine 2.4 (X = CHa. R = C CHPhNHO CK OCH -NMe2) has been introduced by Koga and Yasukata [993]. This amine effects the enantioselective protonation of achiral lithium enolates prepared from racemic 2-alkyl- 1-tetralone trimethylsilylethers by the action of MeLi-LiBr in toluene. In the absence ofLiBr, no asymmetric induction is observed (Figure 4.6). 

The palladium-catalyzed coupling of vinyl triflates with amides, carbamates, and sulfonamides has been reported by researchers at Merck.119 They identified Xantphos as the best ligand for this reaction. The product enamides serve as valuable synthetic intermediates as they can undergo asymmetric hydrogenation to give enantiopure amines. 

The cyclopropanation of a, (3-unsaturated carbonyls can be achieved using metal-free ylides. This is an attractive strategy avoiding the use of expensive metal-based catalysts and potentially hazardous diazo compounds. Two main approaches to the asymmetric ylide-mediated cyclopropanation have been developed, both utilising enantiopure amines as catalysts. 

The production of enantiopure amines has received growing attention in recent years because chiral amines have great potential as building blocks in drug... 

A one-pot, two-step procedure has been developed involving KR of a racemic mixture of an a-chiral primary amine employing m-transaminase to yield an intermediate ketone, which is then stereoselectively transformed into an enantiopure amine in high yield by reductive amination (Scheme 4.46) [101],... 

Oldenhuis NJ, Dong VM, Guan Z (2014) From racemic alcohols to enantiopure amines Ru-catalyzed diastereoselective amination. J Am Chem Soc 136(36) 12548-12551... 

The answer suggests the Michael-type asymmetric addition of an enantiopure amine or its more reactive anion to enone to 23b. The authors used a lithium amide reagent for the addition to obtain the key chiral intermediate 23c (Scheme 3.9) [14]. The selected (S)-configuration of the phenyl ethylamino unit in the chiral amide anion induces the (7 )-configuration in the precursor of —)- R)-sitagliptin. 

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