Amino-alcohols and Related Compounds

With a plethora of natural products including amino- and imino-sugars plus hydroxylated amino-acids in the literature it is hardly surprising that much research effort has been devoted to the syn- 

Indeed, reliable methods for selective ]J-nucleophilic attack at C,-155 156 

The reagents used in the Sharpless epoxidation were also employed in the resolution of racemic B-hydroxyamlnes facilitated by enantioselective N-oxide formation.  

As an alternative to the above approach, intramolecular Michael additions of -carbamates occupying allylic and homoallyllc positions relative to a,B-unsaturated esters as a means of diastereo-selective amination of acyclic systems appears to have much potential1, 2-syn-Cyclisations of both erythro- and threo-y -carbamoyloxy-a,B-unsaturated ester derivatives afforded trans-isoxazolidines which could be transformed into N-acetyl-D,L-acosa-mine and N-benzoyl-D,L-3-epl-daunosamine respectively. However, although the expected 1,3-syn cyclisation was observed for the erythro-6-0-carbamoyloxy-a,B-ester, this leading to the synthe-sis of N -benzoyl-D, -ristosamine, the corresponding threo- 

The allylic amine derivative (27) was used to prepare three of the four diastereomers of 3-amino cyclopentane-1,2-diol, with the remaining one being made from the readily available epoxide 

Asymmetric reduction of or y-functionalized alkyl aryl ketones provides a wide variety of chiral amino alcohols. Commercial -chloropropiophenone is reduced with borane-tetrahydrofuran adduct catalyzed by oxazaborolidine 45 to provide the chlorohydrin in over 99 % yield with 94 % ee. The resulting alcohol is a key intermediate for synthesis of the R form of fluoxetine (Prozac ), a serotonin-uptake inhibitor [53]. Using hydrogenation processes the functionalized amino ketones are converted directly into the respective products [8, 43e], 

Other chiral phosphine/transition metal complexes catalyze the hydrogenation of a-pyridyl ketones (to biologicaly active amino alcohols like (/ ,S)-Mefloquine, an antimalarial agent (Hoffmann-La Roche [30]) or of a-benzamide ketones to 

The Sharpless asymmetric epoxidation of allyl alcohol gives the glycidol derivative 61 in 90% ee after in situ tosylation of 60 [63]. This process is working on a multiton-a-year scale (Arco Co., USA), facilitating the synthesis of a variety of /0-blockers. Asymmetric dihydroxylation of the allyl ether 63 catalyzed by a combined system of OSO4 and the cinchona alkaloid-based ligand 65 allows the commercial synthesis of the propranolol intermediate 64 in 91 % (Sepracor Co., USA) [64]. 

The enantioselective ring opening of epoxides with salen-Cr complexes yields intermediates for the manufacture of ( )-9-[2-(phosphonomethoxy)propyl]ade-nine [67] (a prophylactic against SIV infection). Os-catalyzed asymmetric amino-hydroxylation (ligand modified by cinchona alkaloids) leads to a-hydroxy-j6-phenylalanine, a derivative for the C13 chain of taxol [68]. 

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Reaction with Amino Alcohols and Related Compounds. Both secondary and tertiary carbamates bearing a vicinal hydroxyl group react with carboxylic acids in the presence of DEAD and TPP to afford the corresponding esters with inversion of configuration (eq 34). Reaction of N-t-butoxycarbonylserine with methanol, DEAD, and TPP gives the corresponding methyl ester in >98% yield (eq 35). Without methanol, TV-benzyloxycarbonyl- or A-f-butoxycarbonylserine reacts with the preformed adduct of DEAD and TPP to afford the P-lactone (eq 35). The W-protected serine methyl ester (37a) and threonine methyl ester (37b) react with DEAD and TPP to give the dehydrated products (38a) and (38b) (eq 36). ... 

As already mentioned dielectric constant measurements have given good evidence of the presence of dipole ion in aqueous or alcoholic solutions of amino acids and related compounds. The subject has been studied by Hedestrand 0 and Devoto,10 but most recent and important investigations have been carried out by Wyman and McMeekin.11 12 These authors found for aqueous solutions of amino acids and peptides that the dielectric constant is accurately a linear function of the concen-... 

Konev > and co-workers have reported the luminescence properties of the aromatic amino acids and related compounds in a number of nonpolar solvents and in solid films of polyAdnyl alcohol. No surprising features are found in these media the results in polyvinyl alcohol are very similar to those in frozen aqueous solutions whereas those in nonpolar solvents incapable of forming hydrogen bonds differ by showing the expected blue shifts and additional fine structure. 

Bartoli recently discovered that by switching from azide to p-anisidine as nucleophile, the ARO of racemic trans- 3-substituted styrene oxides could be catalyzed by the (salen)Cr-Cl complex 2 with complete regioselectivity and moderate selectivity factors (Scheme 7.36) [14]. The ability to access anti-P-amino alcohols nicely complements the existing methods for the preparation of syn-aryl isoserines and related compounds [67] by asymmetric oxidation of trans-cinnamate derivatives [68]. 

Glycols and related alcohols In contrast to aliphatic monoalcohols (1), 1,2-glycols and related compounds (2-methoxy alcohols, 1,2-amino alcohols) can be easily oxidized by the direct electrochemical method [12]. For example, 1,2-cyclopentanediol (9) affords diacetal (10) in 56% yield as the main product (Eq. 3). 

Borane and aluminum hydrides modified by chiral diols or amino alcohols are well-known, effective reagents for the stoichiometric enan-tioselective reduction of prochiral ketones and related compounds (34). Reduction of prochiral aromatic ketones with the Itsuno reagent, which is prepared from a chiral, sterically congested /3-amino alcohol and borane, yields the corresponding secondary alcohols in 94-100% ee... 

The p-amino-a-hydroxy esters have been converted to diamino acids [88, 89] and related compounds like the nitrogen-substituted azetidinone shown in Scheme 13, a key structure in the synthesis of the commercially available antibiotic loracarbef [90] by substitution of the alcohol moiety with an azide. Several approaches have been used to achieve this transformation. Mesylation of the alcohol followed by substitution with sodium or trimethylsilyl azide provided cis-diamino acids [88,89]. trans-Diamino acids were obtained by ring opening of the aziridine [88] or by inversion of the alcohol bearing carbon followed by substitution under Mitsunobo conditions [90]. 

A route to pyrroles illustrated by the preparation of 292 involves initial treatment of the nitroketene-5, 5 -acetal 293 with an organometallic reagent, followed by conversion of the resulting alkene 294 to the enamine 295, and final annulation to the target heterocycle (Scheme 34) <1998T12973>. A related approach featuring constmction of /3-hydroxyenamines from 1,3-dicarbonyl compounds and /3-amino alcohols, and subsequent palladium-catalyzed cyclization to pyrroles, has been reported <1996TL9203>. 

According to Rizzi (2000) furfuryl mercaptan (1.128) and related compounds are readily formed by reactions of furfuryl alcohols, formed in Maillard reaction, and sulfur-containing amino acids at acid pH. 

Carbonyi reductions. In an alcohol solvent sodium reduces ketones, esters, and related compounds. 3-Anisyl-methylenecamphor gives 3-en-(p-methoxybenzyl)-isoborneol, which is a potential chiral auxiliary. 1,3-Amino alcohols are obtained from )3-enamino ketones, but there is lack of stereoselectivity in the reduction. 

Alkaloids, Amino Alcohols, and Amino Acids. Their Derivatives and Related Compounds... 

The peptaibol antibiotics are a group of linear oligopeptides (of 15 to 24 residues) characterised by the presence of a high content of a-amino isobutyric acid (Aib) residues and an amino alcohol group at the C-terminus. These substances are frequently obtained as a complex mixture of closely related compounds. For example... 

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