Hydroxy amines from /3-amino aldehydes

Polar C=Y double bonds (Y = NR, O, S) with electrophilic carbon have been added to suifinic acids under formation of sulfones. As in the preceding section one must distinguish between carbonyl groups and their derivatives on the one hand, and carboxylic acids (possessing leaving groups at the electrophilic carbon) on the other. Aldehydes " of sufficient reactivity—especially mono-substituted glyoxals - —and their aryl or arylsulfonyl imines have been added to suifinic acids (in a reversible equilibrium) to yield a-hydroxy or a-amino sulfones the latter could also be obtained from the former in the presence of primary amines (equation 26). 

Though not so general as the reactions we have just seen, the catalysed addition of dialkyl zincs to certain aldehydes sets a new standard for catalysis that needs some explaining. Dialkyl zincs add to the pyrimidine aldehyde 216 under catalysis from amino alcohols, amino acids such as leucine 219, hydroxy acids, and simple secondary alcohols or amines such as 218 to give enantiomerically enriched alcohols 217. Plain sailing so far, except for the extraordinary range of catalysts. 

Diethoxy a-hydroxy-benzylphosphonate has been reported to undergo nucleophilic substitution with primary amines to give a-aminophosphonates (Scheme 184) " Primary aromatic amines have been prepared from arylboronic acids in the presence of 0-(2,4-dinitrophenyl)hydroxylamine. " Reaction of iV-t-butanesulfinyl a-haloimines with alkoxides has been reported to give iV-t-butanesulfinyl 2-amino acetals that are precursors for TMSOTf-promoted synthesis of iV-protected a-amino aldehydes and ketones and for the HCl-promoted synthesis of 2-amino acetal hydrochlorides and a-amino ketone and a-amino aldehyde hydrochlorides (Scheme 185). " ... 

Although it is reported that the U-5C-4CR can work well with nucleophiles other than methanol, such as primary or secondary amines, the only examples reported in the literature are those where trifunctional a-aminoacids such as lysine [67] or homoserine [66] or bifunctional aldehydes such as glycolaldehyde [65] are employed. In these cases, the side-chain amino or hydroxy group acts as the nucleophile and opens the cyclic intermediate generating the corresponding lactams or lactones. A less nucleophilic solvent such as trifluoroethanol is usually employed, in order to maximize the intramolecular attack. The observed stereoselectivities are, apart from a few examples [66], usually not very high this could be due to different factors (a) the side chains of the a-amino acids are not very bulky (b) the intramolecular nucleophilic attack could be faster than the methanol attack and the cyclic intermediate could not equilibrate to the thermodynamically favored isomer (c) the intramolecular nucleophilic attack on the more stable diastereoiso-meric cyclic intermediate could be kinetically less favored. 

Novel nor-seco baccatin 99 was synthesized in 92% yield through oxidative cleavage of the A ring of 14-OH-DAB (75) with periodic acid via the hydroxy ketone intermediate 100 (Scheme 19). Protection of the 7-hydroxyl of 99 as TES ether followed by reduction of the aldehyde with sodium borohydride yielded nor-seco baccatin alcohol 101 in 80% yield. Nor-seco 13-amino-baccatins 102 and 103 were synthesized from 101 and 99a via the Mitsunobu reaction and reductive amination, respectively, in high yields (Scheme 20). 

Also, the primary amine moities of polar lipids catalyze the aldol condensation of Cm-Cig aldehydes resulting from plasmalogen hydrolysis, thus forming a,3-unsaturated aldehydes (l2t). Phosphatidyl ethanolamine reacted with propanal and n-hexanal forming phosphatidyl l-(2-hydroxyethyl)-2-ethyl-3,5-dimethyl pyridinium, and phosphatidyl-1-(2-hydroxy ethyl)-2-hexyl-3,5-dipentyl pyridinium, respectively (125). The peridinium ring is formed by the reaction between one mole of amino-N of phosphatidyl ethanolamine and three moles of n-alkanals. The same reaction took place in the synthesis of substituted pyridines by condensation of carbonyl compounds with ammonia (126, 127). 

A large number of oc-amino sulfonic acids have been prepared from the hydrogen sulfite adducts ( -hydroxy sulfonic acids) and ammonia or amines at or slightly above room temperature. 976They are very important intermediates in the Knoevenagel-Bucherer form of the Strecker amino acid synthesis (cf. page 877). In this synthesis the aldehyde-bisulfite compounds are converted by ammonia or amines into a-amino sulfonic acids and thence by alkali cyanide or hydrogen cyanide into oc-amino nitriles, which are then hydrolysed ... 

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