Hydroxy aldehydes from enamines

Synthesis from 7-Hydroxygeranyl/-neryl Dialkylamine. The starting material can be obtained by treatment of myrcene with a dialkylamine in the presence of an alkali dialkylamide, followed by hydration with sulfuric acid. The 7-hydroxy-geranyl/-neryl dialkylamine isomerizes to the corresponding 7-hydroxy aldehyde enamine in the presence of a palladium(II)-phosphine complex as catalyst. Hydrolysis of the enamine gives 7-hydroxydihydrocitronellal [70]. 

The reaction of NO with a wide variety of enamines, derived from the respective aldehydes and ketones can produce N-hydroxy-N-nitrosamine (Scheme 3.10) [137]. These compounds are relatively stable to thermal decomposition and do not release copious volumes of NO upon adding to concentrated mineral acids. However, on dissolution in aqueous buffer at pH 7.4 and 37 °C, a slow release of NO could be detected by the chemiluminescence method. 

These are the most favourable of all and the precursors, such as the hydroxy acids, e.g. 15, cannot usually be isolated, though the carboxylate salts are stable. The only important thing is to get the oxidation level of the precursor right. Using cyclic amines as examples, a fully saturated ring 45 would come from an alkylation reaction on 46 X = a leaving group. Imines 47 or enamines 49 would come from aldehydes or ketones 48. 

Simple enamines cannot be deprotonated directly at the a-position due to their low acidity, but starting from a-chloroenamines 685, a-lithioenamines 686991 have been prepared by chlorine-lithium exchange using an arene-catalyzed lithiation992. The treatment of compounds 685 with an excess of lithium and a catalytic amount of 4,4 -di-tert-butylbiphenyl (DTBB) in THF at —90 °C allowed the preparation of intermediates 686, which were trapped with a variety of electrophiles (Scheme 177). For aldol reactions, the arene-catalyzed lithiation has to be performed in the presence of aldehydes (Barbier conditions) at —40 °C. These adducts were transformed into a-hydroxy ketones after acid hydrolysis with hydrochloric acid or silica gel. 

V. Enamines. Reactions of the enamines from condensation of piperidine or morpholine with an aldehyde with p-benzoquinone gives 2,3-dihydro-5-hydroxy-2-piperidino(or morpholino)benzofurans (146),... 

Highly functionalized tetrahydropyran-4-ones can be obtained through a silyl enol ether Prins cyclization promoted by a condensation reaction of hydroxy silyl enol ethers with Lewis-acid-activated aldehydes, with high diastereoselectivity (14JOC8733). Spirooxindole tetrahydropyran-4-ones are obtained from oxa-DA reaction of acyclic a,P-unsaturated methylke-tones and isatins mediated by a bifunctional enamine-metal Lewis acid catalyst, in good yields and moderate stereoselectivities (14S1339). 

The first section of this chapter describes the preparation and several synthetic applications of a-fluoroalkyl P-sulfmyl enamines and imines the second deals with the chemistry of di- and trifluoropyruvaldehyde A, 5-ketals, stereochemically stable synthetic equivalents of P-di and P-trifluoro a-amino aldehydes, which can be prepared from the corresponding p-sulfinyl enamines the third overviews the preparation of chiral sulfinimines of trifluoropyruvate and their use to prepare a library of a-trifluoromethyl (Tfm) a-amino acids the fourth section is mainly dedicated to the asymmetric synthesis of monofluorinated amino compounds, using a miscellany of methods such as MifstmobuAike azidation of P-hydroxy sulfoxides, ring opening of fluoroalkyl epoxides with nitrogen-centered nucleophiles and 1,3-dipolar cycloadditions with chiral fluorinated dipolarophiles. 

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