Stereoselectivity amination

A chiral O-phosphinylhydroxylamine-type reagent, such as (2R,4S,5R)-2-[0- N,N-dimethylhydroxylamino)]-3,4-dimethyl-5-phenyl-l,3,2-oxazaphospholidin-2-one 4e, was also used for stereoselective amination of carbanions (equation 23)"°. 

As an extension of the use of chiral 0-phosphinylhydroxylamine 4e for stereoselective amination, the reaction of lithium enolates with 4e was also tried. However, low levels of enantiomeric purity were obtained (Scheme 47)". ... 

The synthesis of the protected 5-hydroxy P-amino acids 91 required a stereoselective amination of the vinyl sulfoximine 4 (Scheme 1.3.29). Carbamoylation of alcohols 4 with trichloroacetyl isocyanate afforded carbamates 86 in high yields. 

Evans, D. A., Britton, T. C., Dellaria, J. F., Jr. The asymmetric synthesis of a-amino and a-hydrazino acid derivatives via the stereoselective amination of chiral enolates with azodicarboxylate esters. Tetrahedron 1988, 44, 5525-5540. 

P-Ketoallylsilanes (220) have been synthesized by the Horner-Emmons reaction starting from novel silylated ketophosphonates and various aldehydes and converted into a-methylene-Af-(ethoxy-carbonyl)-P-amino ketones (221) (Scheme 86). Stereoselective amination of chiral silane (220, = isopropylideneglyceryl) gave a 90%... 

Chiral amines have been attracting attention as an important composition, particularly for pharmaceutical products. The organic synthetic methods of optically active amine compounds have been developed through the traditional resolution of racemic amines with the formation of diastereomer salts using an optically active mandelic acid or tartaric acid. Enzymatic synthesis has mainly used lipase and S- or R-stereoselective amine transaminase (AT) [29-31] (Figure 19.7). Turner et al. successfully synthesized chiral (R)- and (S)-amines by kinetic resolution using a combination of stereoselective AT and d- or L-amino acid oxidase (AAOx) [32] (Figure 19.7). However, the theoretical yield of the products has been limited to 50% in the kinetic resolution. 

We described the development of a valuable l -stereoselective amine oxidase for the synthesis of (S)-amine through a deracemization reaction [38]. 

Yasukawa, K., Nakano, S., and Asano, Y, "Tailoring D-Amino acid oxidase from the pig kidney to R-stereoselective amine oxidase and its use in the deracemization of -methylbenzylamine." Angew. Chem. Int. Ed., 53, 4428-4431 (2014). 

The condensation of aldehydes or ketones with secondary amines leads to "encunines via N-hemiacetals and immonium hydroxides, when the water is removed. In these conjugated systems electron density and nudeophilicity are largely transferred from the nitrogen to the a-carbon atom, and thus enamines are useful electroneutral d -reagents (G.A. Cook, 1969 S.F. Dyke, 1973). A bulky heterocyclic substituent supports regio- and stereoselective reactions. 

The Birch reductions of C C double bonds with alkali metals in liquid ammonia or amines obey other rules than do the catalytic hydrogenations (D. Caine, 1976). In these reactions regio- and stereoselectivities are mainly determined by the stabilities of the intermediate carbanions. If one reduces, for example, the a, -unsaturated decalone below with lithium, a dianion is formed, whereof three different conformations (A), (B), and (C) are conceivable. Conformation (A) is the most stable, because repulsion disfavors the cis-decalin system (B) and in (C) the conjugation of the dianion is interrupted. Thus, protonation yields the trans-decalone system (G. Stork, 1964B). 

In Diels-Alder reactions a nitroolefin may function as an electron-deficient ene com-onent or a 1,2-dihydropyridine derivative may be used as a diene component. Both types of iactants often yield cyclic amine precursors in highly stereoselective manner (R.K. Hill, 1962 i. BOchi, 1965, 1966A). 

Allylic phosphates are used for carbonylation in the presence of amines under pressure. Carbonylation of diethyl neryl phosphate (389) affords ethyl homonerate (390), maintaining the geometric integrity of the double bond[244]. The carbonylation of allyl phosphate in the presence of the imine 392 affords the /3-lactam 393. The reaction may be explained by the formation of the ketene 391 from the acyl phosphate, and its stereoselective (2 + 2] cycloaddition to the imine 392 to give the /3-lactam 393(247],... 

Note that the relative spatial arrangement of the phenyl, amine, and hydroxyl functionahties are identical for (R)-alprenolol and (5)-sotalol. In addition to P-blocking activities, some of these compounds also possess potent local anaesthetic activity (see Anesthetics). The membrane stabilizing activity, however, is not stereoselective and correlates directly with the partition coefficient (hydrophobicity) of the compound. 

Retention and stereoselectivity on the BSA columns can be changed by the use of additives to the aqueous mobile phase (30). Hydrophobic compounds generally are highly retained on the BSA, and a mobile-phase modifier such as 1-propanol can be added to obtain reasonable retention times. The retention and optical resolution of charged solutes such as carboxyUc acids or amines can be controlled by pH and ionic strength of the mobile phase. 

The milder metal hydnde reagents are also used in stereoselective reductions Inclusion complexes of amine-borane reagent with cyclodexnins reduce ketones to opucally active alcohols, sometimes in modest enantiomeric excess [59] (equation 48). Diisobutylaluminum hydride modified by zmc bromide-MMA. A -tetra-methylethylenediamme (TMEDA) reduces a,a-difluoro-[i-hydroxy ketones to give predominantly erythro-2,2-difluoro-l,3-diols [60] (equation 49). The three isomers are formed on reduction with aluminum isopropoxide... 

Triflates of titanium and tin are effective catalysts for various condensations of carbonyl compounds [I2I, 122, 123, 124, 125] Claisen and Dieckmann type condensations between ester functions proceed under mild conditions in the presence of dichlorobis(trifluoromethanesulfonyloxy)titaiiiuin(rV) and a tertiary amine (equations 59 and 60) These highly regio- and stereoselective condensations were used successfully m the synthesis of carbohydrates [122]... 

Greater stereoselectivity for the formation of equatorial amines has been found in the reduction of enamines with formic acid or formamides (553-559). The selective formation of 3-a-amino-5- -steroids by this method and of 3- 3-amino-5- 3-steroids by catalytic reduction (5<50) of the corresponding enamines is of interest. 

This was ihe first investigation of stereoselective formation of geometric isomers of tertiary amines. The authors suggested most enamine systems should be subject to considerable stereochemical control. 

The isomerization of an allylic amine to an enamine by means of a formal 1,3-hydrogen shift constitutes a relatively small structural change. However, this transformation could be extremely valuable if it could be rendered stereoselective. In important early studies, Otsuka and Tani showed that a chiral cobalt catalyst, prepared in situ from a Co(ii) salt, a chiral phosphine, and diisobutylaluminum hydride (Dibal-H), can bring about the conversion of certain pro-chiral olefins to chiral, isomeric olefins by double bond migra-... 

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