Synthesis of Amino Alcohols

The use of glyceraldehyde as the carbonyl component is also highly effective, 

2-Methyl-1 -pyrrolidino-1 -pentene 2-methyl-1 -pyrrolidino-pentan-2-ol 64 

M-Tosyl-5-aminocyclooctanol is prepared [4] in excellent yield by reacting B-octyl-9-BBNwithhypervalentiodine compound [M-(p-toluenesulfonyl)imino] phenyliodinane at room temperature (Eq. 6.20). 

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Pd metals immobilized on SBA-15 and NaY were applied as catalysts in the synthesis of amino alcohol. These catalysts afford a high level of enantioselectivity in the asymmetric hydrogenation of a-keto alcohol to corresponding amino alcohol. The large peilladium metal exhibited higher catalytic activity and enantioselectivity than well dispersed one over porous supports in the hydrogenation. 

A classical approach to driving the unfavorable equilibrium of an enzymatic process is to couple it to another, irreversible enzymatic process. Griengl and coworkers have applied this concept to asymmetric synthesis of 1,2-amino alcohols with a threonine aldolase [24] (Figure 6.7). While the equilibrium in threonine aldolase reactions typically does not favor the synthetic direction, and the bond formation leads to nearly equal amounts of two diastereomers, coupling the aldolase reaction with a selective tyrosine decarboxylase leads to irreversible formation of aryl amino alcohols in reasonable enantiomeric excess via a dynamic kinetic asymmetric transformation. A one-pot, two-enzyme asymmetric synthesis of amino alcohols, including noradrenaline and octopamine, from readily available starting materials was developed [25]. 

Acid hydrolysis of tetrahydrooxazines 407 is well known and widely used for the synthesis of amino alcohols 408 or for the enantioselective synthesis of aldehydes 409, which can be transformed to carboxylic acids by mild oxidation [78AHC(23)1 87JCS(P1)515, 87T4979 90JOC2114]. 

The procedure reported here, which is that of Hassner and Heathcock,3 is more convenient than the Wenker synthesis of aziridines4 and appears to be more general.5 It represents a simple route from olefins to aziridines (via 8-iodo carbamates).356 Aziridines are also useful as intermediates in the synthesis of amino alcohols and heterocyclic systems.5,7-9... 

For reviews of the stereochemistry and mechanism, see Caro Boyer Lamaty Jaoucn Bull. Soc. Chim. Fr. 1983,11-281-1T303 Boone Ashby Top. Siereochem. 1979, II, 53-95 Wigfield Tetrahedron 1979, 35, 449-462. For a review of stereoselective synthesis of amino alcohols by this method, see Tramontini Synthesis 1982, 605-644. 

The practicality of the method was enhanced by the fact that simple extraction provided access to both the hemiester product and the alkaloid without chromatography, and the recovered cinchona alkaloid could be reused with no deterioration in the ee or yield of the reactions. This method has found use by other groups in the synthesis of / -amino alcohols and in natural product synthesis [173, 174], and has recently been reported as an accepted method in Organic Syntheses [175]. 

Figure 4. Synthesis of amino alcohols on a solid phase as potential ligands for the addition of diethylzinc to aldehydes.

This catalytic system was successfully applied to the alkynylation of tosyl aziridine with adjacent ether functionality this should provide a promising method for the synthesis of amino alcohols. Treatment of tosyl aziridine 81 with PhC CLi in the presence of catalytic Mc3Al in toluene at 0 °C for 5 h gave rise to the corresponding alkynylation product 82 in 66 % yield (Sch. 53), whereas reaction in the absence of Me3Al proceeded sluggishly under similar reaction conditions (7 % yield). The control experiment with simple aziridine 83, in which addition of catalytic McaAl had almost no influence on the reaction rate, supports the proposed catalytic cycle its efficacy is based on the formation of the pentacoordinate organoaluminum complex. 

An asymmetric synthesis of amino alcohols by asymmetric addition of Grignard reagents to chiral a-bromoglycine esters provides a convenient synthesis of a-amino esters (Scheme 4.8, [99]). Hydrolysis of the product ester produces racemized amino acids, but reduction affords amino alcohols that can be subsequently oxidized to the amino acids with no loss of enantiomeric purity. Note that in the proposed transition structure, the phenyl effectively shields the Re face (toward the viewer) of the imine, which is chelated to the carbonyl by magnesium halide formed in the dehydrohalogenation. 

SCHEME 18 Synthesis of amino alcohol 50 from D-mannitol. 

Scheme 17.18 Diastereoselective synthesis of amino alcohols via r2.S1-Wittig rearrangement including tetrahydroazepinones.

Regiospecific nucleophilic ring opening of oxetanes to 3-silyl-oxyisocyanides with trimethylsilyl cyanide/Znl2 in dichloromethane has been reported, and this has led to the synthesis of amino-alcohols by hydrolysis of the isocyanide group. ... 

Table 6.23 Synthesis of amino alcohols from p,p-disubstituted enamines [3]...

Protection of the amino group in allyl amines may be useful to avoid side reactions, as shown in the synthesis of amino alcohols (Scheme 5.113) [98]. 

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