P-Aminoalcohols

Reactions of benzylic a,P-aminoalcohols and a-hydroxyazindines with Olah s reagent provide a highly efficient way to a P-fluoroamines, a-fluoro-azindines, and ot,Y-difluoroamines [dS] (equations 43 and 44)... 

It has been proposed that aziridines may be more widespread in biological systems than is generally realized [190]. Many drugs such as ephedrine (124 Scheme 11.18) and pronethalol (125) and endogenous metabolites such as adrenaline (126) contain a P-aminoalcohol moiety, which may act as a precursor to an aziridine metabolite that may explain the known carcinogenicity of some of these compounds such as pronethalol. 

The proline-catalyzed reaction has been extend to the reaction of propanal, butanal, and pentanal with a number of aromatic aldehydes and proceeds with high syn selectivity.197 The reaction can also be carried out under conditions in which the imine is formed in situ. Under these conditions, the conjugative stabilization of the aryl imines leads to the preference for the aryl imine to act as the electrophile. A good yield of the expected P-aminoalcohol was obtained with propanal serving as both the nucleophilic and the electrophilic component. The product was isolated as a 7-amino alcohol after reduction with NaBH4. 

Oxazolidinones have also been used as intermediates in simple transformations utilising their peculiar reactivity. The absolute configuration of WBoc-P-aminoalcohol 213 can be easily inverted via Sn2 cyclisation to oxazolidinone 214 <00TL10071>. Treatment with Olah s reagent (HF-Pyridine) of 4-alkyl-5,5-diphenyl-oxazolidinones 216 afforded the corresponding a-(fluorodiphenylmethyl)alkylamines 217 <00TA2033>. 

Considering the preparative aspects, the main synthetic pathway is the reaction of a p-aminoalcohol with a thiocarbonyl-source under basic conditions. The different approaches are summarized in Scheme l.27 29... 

Catalyst Additive Time (h) Yield [%f Ee [%] Confign. of P- aminoalcohol... 

Rao et al. [100] for the first time report the biomimetic approach for the synthesis of a single enantiomer of p-aminoalcohol. In this approach p-cyclodextrin formed by the inclusion of complex 77 with racemic aryloxyepoxide which reacted enantioselectively with amines imder solid state condition to give the product in 100% ee and 70-79% isolated yield. The yield which was above 50% was explained in terms of continuous racemization of the... 

The chiral ligand (44) was prepared starting from the cyclic a-amino acid (S)-proline80). Recently, similar chiral catalysts and related molybdenum complexes involving optically active N-alkyl-P-aminoalcohols as stable chiral ligands and acetylacetone as a replaceable bidentate ligand, were designed for the epoxidation of allylic alcohols with alkyl hydroperoxides which could be catalyzed by such metal complexes 8,). 

P-Aminoalcohols may be generated from (3-azidoalcohols, which are commonly made from the opening of epoxides with azide ion as shown in Scheme 13 (91TL2533). After conversion of the alcohol... 

Another group of applications consists of electrosynthesis of substances that can be otherwise synthesized only with difficulty. The chemical reduction of p-aminoketones is complicated by the elimination of these compounds. A polarographic two-electron wave in acidic solution, corresponding to the reduction of carbonyl grouping to p-aminoalcohol... 

Ring opening of 2-silylaziridines synthesis of p-silylamines and a-silyl-p-aminoalcohols... 

The synthesis of thiazoline based nucleosides has been reported. The synthesis starts with methyldifluorodiethoxyphosphonodithioacetate (79), which is coupled with P-aminoalcohols to... 

An alternative ring construction approach to 1,4-oxazepin-7-ones (e.g. 241) utilises the Baylis-Hillman product 240, subsequent reaction with a p-aminoalcohol, and ester hydrolysis followed by DCC-mediated intramolecular coupling to afford 241. This sequence can be generalised to give a range of analogues [02S2232],... 

Corma et al have anchored Rh(I), Ru (II), Co(II) and Ni(II) chiral complexes based on p-aminoalcohols such as (L) prolinol onto silica and modified USY-zeolites (scheme 3) to perform enantioselective hydrogenation of the same prochiral alkenes than shown in scheme 2.20,34... 

Ravina, E., Montands, J. M., Seco, M. C.. Callcja, J. M., and Zar/osa, M.. Synthesis and potential antiparkinsonism activity of some tcrliaiy substituted P-aminoalcohols containing a bcnzofiiran nucleus, Chim. Ther, 8. 182, 197.3. 

Vanadium(IV) Schiffsbase complexes derived from P-aminoalcohols 7.62 and vanadyl acetylacetonate have been used to oxidize different substrates to chiral sulfoxides. 

Cyclization by formation of the C4-C5-bond is demonstrated by intramolecular alkylation of the dianion of methylsulfonamide 203 to give sultam 204. This method has been applied towards the synthesis of chiral sultams, which are valuable auxiliaries <03OL4175>. The required P-chloroalkanesulfonamides 203 are easily accessible from p-aminoalcohols via bis-mesylation and displacement of the 0-mesyl group by chloride. 

A new metal-catalyzed exocyclic carbonylation of cycloimino esters 184 was reported. The reaction proceeded without HI in relatively mild conditions affording the expected N-acyl oxazolidin-2-ones 185 <03OL3955>. An improved procedure for the palladium catalyzed oxidative carbonylation of P-aminoalcohols to oxazolidin-2-ones was published <03JOC601>. 

A simple stereoselective synthesis of /ra i-2-oxazolidinones, such as 187, was reported using a PPhs-CCU-TEA mediated cyclization of M-Boc-P-aminoalcohols 186. In the same work cis derivatives were converted into tram by the use of DBU <03TL6323>. 

The hydrogenolysis/decarboxylation/asymmetric protonation reaction cascade of acyclic benzyl P-oxo-esters such as 47 catalyzed by Pd/C with H2 in the presence of a catalytic amount of cinchonine 43 afforded the (S)-ketone 48 with enantioselec-tivities up to 75% ee, similar to previous results obtained with other P-amino alcohols. The reaction was carried out at room temperature in a short reaction time [28]. The best solvent for both yield and ee was ethyl acetate, compared with acetonitrile and THF. Comparative performances of cinchona alkaloids with other commonly used P-aminoalcohols are displayed on Scheme 7.22. 

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