1,3-Amino alcohols, from isoxazolines

Aliphatic nitro compounds are versatile building blocks and intermediates in organic synthesis,14 15 cf. the overview given in the Organic Syntheses preparation of nitroacetaldehyde diethyl acetal.16 For example, Henry and Michael additions, respectively, lead to 1,2- and 1,4-difunctionalized derivatives.14 18 1,3-Difunctional compounds, such as amino alcohols or aldols are accessible from primary nitroalkanes by dehydration/1,3-dipolar nitrile oxide cycloaddition with olefins (Mukaiyama reaction),19 followed by ring cleavage of intermediate isoxazolines by reduction or reduction/hydrolysis.20 21... 

Dipolar cycloadditions between nitrones and alkenes to give isoxazolines are very important reactions in organic synthesis, because 1,3-amino alcohols can be synthesized from isoxazoline derivatives. Jprgensen and co-workers reported catalytic asymmetric... 

Isoxazolines have also been converted into 1,3-amino alcohols by polymethylhydrosiloxane (PMHS)-Pd(OH)2/C. When the reduction was performed in the presence of (B0C)20, WBOC protected compounds were directly achieved (BOC = f-butoxycarbonyl). For example, WBOG-y-amino alcohols 132 were synthesized from the corresponding isoxazolines 131 in one step and 78-88% yield (Equation 15) <2004SL1303>. 

Isoxazolidines, Isoxazolines, Oxazolines, and Oxazines isoxazoiidines, easily obtained by cycloaddition of nitrones to olefins, are reduced to 1,3-amino alcohols by reaction with LAH in ether media. The synthesis of racemic sedridine from 3.256 is illustrative [TA2] (Figure 3.100). 

Burn at Hoffmann-La Roche chose to couple the two monomeric units via an intramolecular Wadsworth-Emmons reaction rather than lactonization (see Scheme 4.16). Thus dithiane 70, obtained by formylation of the anion derived from 69, underwent a regiospecific 1,3 dipolar cycloaddition with acetonitrile oxide to afford isoxazoline 71. Dibal reduction to the related amino alcohol followed by optical resolution with D-camphorsulfonic acid led to the isolation... 

Homoallyic amines. Isoxazolines derived from allylic phosphine oxides can be converted by nickel boride to the saturated 1,3-amino alcohols. On further reaction, elimination of phosphinic acid occurs. 

In this volume we present five selected contributions by well-known authors, each an authority in his field. The first chapter deals with construction of isoxazolines (dihydroisoxazoles) via 1,3-dipolar cycloadditions of nitronates or of nitrile oxides generated from nitroalkanes. This includes inter- as well as intramolecular processes. Many of these heterocycles possess important synthetic and biological properties and are shown to lead to stereo- and re-gioselective introduction of multifunctional molecules such as amino alcohols, )6-amino acids, aldols, nitriles, and others. 

A new synthesis of the hitherto not easily prepared silylated 2-nitro-alcohols (9) from nitroalkanes has allowed the development of an efficient route to 2-amino-alcohols by reduction with lithium aluminium hydride (Scheme 8). Two syntheses of y-amino-alcohols have added significantly to the methodology available for the preparation of such compounds. In one, the known reduction of the readily available 2-isoxazolines (10) to y-amino-alcohols... 

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