Methylbenzylamines, diastereoselective

Several reports have employed a more traditional approach where the use of enantio-pure chiral amino auxiliaries, that, after the successful Strecker reaction, can be chemically modified to yield the free amino acids. For example, Chakraborty and co-workers have reported the highly diastereoselective addition of trimethylsilyl cyanide to a variety of a-phenylglycinol-derived benzaldimines [16]. (S)-a-Methylbenzylamine has been used as a chiral auxiliary for the asymmetric Strecker reaction [17]. (R)-Phenylglycinol has been utilized as a chiral auxiliary from the asymmetric Strecker reaction products of aldehydes in the synthesis of a,a-disubstituted amino acids [18]. (R)- and (S)-2-Amino-2-phenylethanol were used as chiral auxiliaries in the synthesis of optically pure a-arylglycines [19]. 

The influ nee of reaction conditions on the stereochemistry of the oxidation of optically act ve or racemic Af-diphenylmethylene a-methylbenzylamines 40 with chiral or achiral peroxy acids to oxaziridines was investigated. It was found that asymmetric induction at the ring nitrogen in the resulting oxaziridine from optically active imine 40 does not depend on the nature of the peroxy acid or the solvent. However, the diastereoselectivity seems to be dependent only on the reaction temperature. The ratio of the resulting oxaziridine diastereomers changed by 10% when the reaction temperature was raised from — 30°C to -t-40°C. On the other hand, the enantioselectivity was found to depend on the chirality of the peroxy acid, the temperature, and the solvent. For example, the optical yield of the major oxaziridine diastereomer decreased from 3.4 to 1.3 when the solvent was changed from chloroform to methanol in the oxidation of racemic 40. 

The first enantioselective total synthesis of (-)-tejedine was completed by P.E. Georghiou using a chiral auxiliary-assisted diastereoselective Bischler-Napieralsid cycHzation as one of the key steps.The chiral auxiliary was the commercially available (S)-a-methylbenzylamine, which was coupled to the substrate using the original Schotten-Baumann acylation conditions. The acid chloride was reacted with the chiral amine in a solvent mixture containing aqueous sodium hydroxide and dichloromethane and the desired amide was isolated in excellent yield. 

Another chiral vinylogous urethane, 677, played a central role in the synthesis of (- )-652 by Lhommet and co-workers (Scheme 90) 494). This compound, prepared from (/ )-a-methylbenzylamine (678) (495), was diastereoselectively hydrogenated over platinum oxide to give the amino-ester 679 (de >95%). More significantly, methylation of the anion of 679 under conditions of kinetic control afforded 680 (de ca 98%) in 33% overall yield from the chiral amine 496). Wittig reaction of the aldehyde derivative 681 with the stabilized ylide l-(triphenylphosphoranylidene)-2-heptanone yielded 682 (90%) as a 4 1 mixture of E and Z isomers. When this product... 

Enantiomerically pure neopentylamine derivatives have been prepared from the corresponding ketones by a four-step sequence involving imine formation with (R)-a-methylbenzylamine followed by a highly diastereoselective reduction with sodium borohydride62. 

Chiral P-enamino ester 8 7 was prepared from 2-oxo-cyclopentanecarboxylates and (R)-a-methylbenzylamine [69, 99]. Reduction of 87 with sodium triacetoxyborohydride led to the amino ester 88 with diastereoselectivities of 85% (R=Et) and 67% (R=CH2Ph). After separation of the cis and trans isomers of 88 (R=CH2Ph), the benzyl groups were removed by hydrogenolysis, giving directly pure 89 with ( S,2R) configuration [99]. 

The first synthesis of an optically active a-aminophosphonic acid was reported by Gilmore and McBride [25], Diastereoselective addition of diethyl H-phosphonate to imine, derived from enantiomerically pure a-methylbenzylamine, furnished a-aminobenzylphos-phonic acid enantiomers. 

The high enantio- and diastereoselectivity of but-2-enyl-9-BBN are due to the attack of boron reagent from the si face [18] of iminoester. The si-face attack results from the steric and stereoelectronic effects of the imine and BBN groups. The transition state leading to threo is highly destabilized as compared with the erythro-intermediate (Scheme 9.5). Consequently, in the present reaction the erythro-selectivity is more than 93%. Therefore, the a-methylbenzylamine... 

In early work, Lassaletta et al. described a DKR reaction coupled to the formation of primary amines [98], In a related process, an efficient ATH reaction was reported for the synthesis of an advanced intermediate to a drug for the treatment of human papillomavims infections (Fig. 28). This involves an interesting exo—C=N reduction in an in situ process. The formation of an imine followed by a reduction using a Ru(II)/BlNAP complex was also investigated, as was a diastereoselective method using alpha-methylbenzylamine as a directing group [99]. 

The asymmetric benzylation of enolates derived from the phosphono-propanoamide (206) bearing (S)-a-methylbenzylamine (MBA) moiety easily obtained in a two step reaction from (205), has been examined by Ordonez (Scheme 73). Surprisingly, a reversal of the 7i-facial diastereoselectivity was observed by a change of the kind and number of equivalents of the lithium base. The reaction of the lithium enolate obtained using 2.0 equiv of LDA, LiHMDS or LTMP followed by benzylation with benzyl bromide afforded the (7 ,5)-diastereoisomer (207a), whereas the use of >2.5 equiv of the lithium base (LDA, LiHMDS or LTMP) gave the (5,5)-diastereoisomer... 

The first example of a diastereoselective addition of an H-phosphonate to chiral imines was reported by Gilmore and McBride in 1972. a-Methylbenzylamine was used as a chiral auxiliary, and the reaction carried out at 140 °C led to a 2 1 mixture of diastereomers. Later, the procedure was improved and applied to the synthesis of hapten 87... 

The one-pot, three-component, highly diastereoselective (95 5 dr) reaction of 2-formylbenzoic acid methyl ester (477) with (5)-(479) and (i )-(480) methylbenzylamine and dimethyl phosphite (478) (the Kabachnik-Fields reaction) proceeded under solvent and catalyst free-conditions to afford the corresponding chiral (3i ,105)-(481a) and (35 ,10i )-(481b) isoindolin-1-one-3-phosphonates in good yields and with high diastereoselectivity (Scheme 119). ... 

Another approach in the synthesis of functionalized piperidine alkaloids (—)-coniine (149a) and (—)-pipecoline (149b) started with the imines 147a and 147b using (R)-a-methylbenzylamine as a chiral auxiliary (Scheme 2.34) [57]. Consecutive diastereoselective vinylation and N-aUylation afforded compounds 148a and 148b as two diastereoisomers (71% de, major isomer shown). RCM... 

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