Aldehydes, addition derivatives Grignard reaction

On the other hand, following the same sequences from the differently protected serine-derived nitrone 168, through the formation of hydroxylamines 169, C2 epimers of carboxylic acid and aldehydes are obtained, i.e., (2S,3R)-170 and (2S,3R)-171. Moreover, the syn adducts 164 were exclusively obtained in the addition of Grignard reagents to the nitrone 163, whereas the same reactions on nitrone 168 occurred with a partial loss of diastereoselectivity [80]. Q, j6-Diamino acids (2R,3S)- and (2R,3R)-167 can also be prepared from the a-amino hydroxylamines 164 and 169 by reduction, deprotection and oxidation steps. The diastereoselective addition of acetylide anion to N,N-dibenzyl L-serine phenyhmine has been also described [81]. 

A few 6- and 8-cyanopurines have been prepared and undergo characteristic nitrile addition reactions rather readily. Thus, alkaline hydrolysis produces carboxamides, then carboxylic acids, alcoholysis leads to imidates, ammonolysis to amidines, hydrazinolysis to amidhydrazines, hydroxylamine to amidoximes, and hydrogen sulfide to thioamides. Acid hydrolysis tends to give the decarboxylated acid derivative. Reduction either by sodium-ethanol or, preferably, by catalytic hydrogenation affords aminoalkylpurines and addition of Grignard reagents produces, in the first place, acylpurines. As with aldehydes, most of the compounds examined have been relatively non-polar derivatives. Table 28 lists some reactions and relevant literature. 

Addition to C=N. Chiral amines are synthesized by Grignard reaction of f-butanesulfinamdes. ° An access to p-branched a-amino acids involves addition of RMgX to 2W-azirene-2-carboxylic esters." Nitrones derived from serine and chiral ot-amino aldehydes (thence the amino acids) are sources of a,P-diamino acids and 1,2-diamines, respectively. 

The a,(3-unsaturated ester (8), aldehyde (9), and nitro (10) compounds participate as electrophiles in a number of useful conjugate addition reactions. Copper-catalyzed addition of Grignard reagents provides access to aryl butanoic acid derivatives substituted with an oxetane (equation 1 in scheme 13.7). The ester, aldehyde, and nitro electrophiles also undergo mild Rh-catalyzed additions of aryl and vinyl boronic acids (equation 2 through equation 4 in scheme 13.7). Interestingly, the unsaturated aldehyde participates readily in an amine conjugate addition to afford oxetane substituted 3-amino-acetaldehyde derivatives. 

Diastereoselective additions. The y-substituents of allenyl carbonyl compounds exert stereodirecting effects on the Grignard reaction. On the other hand, the diastereoselectivity observed in the reactions of the aldehydes derived from a serine orthoester and 2-acyl-1,3-dithiane 1-oxides can be attributed to chelation control. 

Conformationally-locked C-nucleosides such as 147 have been reported from Imanishi s laboratory. These were prepared by formation of the C-T-O bond in Mitsunobu reactions, the necessary diols being formed by stereoselective addition of Grignard derivatives of the heterocycles to an aldehyde. Use of lithiated heterocycles gave substantially more of the other epimers of the diols, thus permitting access to the a-anomers after Mitsunobu reaction. The oxazole 147 and the compound without the phenyl group were incorporated into oUgonuc-leotides, and the triplex-forming ability of the these towards a purine sequence of duplex DNA was studied. ... 

The synthetic potential of conjugate additions in the service of molecule syntheses has spurred the development of a host of innovative processes controlled by chiral auxiliaries [28, 29, 31, 33-36). In an early example in this area, Koga reported conjugate additions of Grignard reagents to chiral eni-mine 55, which are readily derived from aldehydes and optically active a-amino esters (Equation 10) [73]. The product aldehyde 56 was obtained in high optical purity (95 % ee) after acidic hydrolysis. The use of the sterically encumbered tert-leucine tert-butyl ester 55 suppresses undesired side reactions such as 1,2-addition and ester addition. 

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