Amino-alcohols from epoxides

The use of a cationic aza-Cope rearrangement in concert with a Mannich cyclization has also been applied to the total synthesis of enantiomerically pure (—)-crinine (359) (205). In the event, nucleophilic opening of cyclopentenoxide with the aluminum amide that was formed on reaction of (/ )-a-methylbenzyl-amine and trimethylaluminum gave the amino alcohol 485 together with its (15,25) diastereomer. Although there was essentially no asymmetric induction in this process, the diastereomeric amino alcohols were readily separated by chromatography, and the overall procedure therefore constitutes an efficient means for the preparation of enantiomerically pure 2-amino alcohols from epoxides. When the hydrochloride salt derived from 485 was treated with paraformaldehyde and potassium cyanide, the amino nitrile 486 was formed. Subsequent Swem oxida-... 

Curini, M. Epifano, F. Marcotullio, M. C. Rosati, O. Zirconium sulfophenyl phospho-nate as a heterogeneous catalyst in the preparation of /1-amino alcohols from epoxides. Eur. J. Org. Chem. 2001, 4149-4152. 

N-Nitrosopiperidine (carcinogen) with oxygen adds photolytically to alkenes to give A(-(2-nitro-alkyl)piperidines. Indirect methods of preparing amino alcohols from alkenes include the well-known trans opening of epoxides with nitrogen nucleophiles and a recent, complementary, cis opening of... 

Mojtahedi et al. (1999) obtained high yields of P-amino alcohols from the reaction of primary and secondary amines with epoxides in the presence of montmoril-lonite KIO clay, under solvent-free conditions and microwave irradiation. 

Due to the abundance of epoxides, they are ideal precursors for the preparation of P-amino alcohols. In one case, ring-opening of 2-methyl-oxirane (18) with methylamine resulted in l-methylamino-propan-2-ol (19), which was transformed to 1,2-dimethyl-aziridine (20) in 30-35% yield using the Wenker protocol. Interestingly, l-amino-3-buten-2-ol sulfate ester (23) was prepared from l-amino-3-buten-2-ol (22, a product of ammonia ring-opening of vinyl epoxide 21) and chlorosulfonic acid. Treatment of sulfate ester 23 with NaOH then led to aziridine 24. ... 

Substitution of an additional nitrogen atom onto the three-carbon side chain also serves to suppress tranquilizing activity at the expense of antispasmodic activity. Reaction of phenothia zine with epichlorohydrin by means of sodium hydride gives the epoxide 121. It should be noted that, even if initial attack in this reaction is on the epoxide, the alkoxide ion that would result from this nucleophilic addition can readily displace the adjacent chlorine to give the observed product. Opening of the oxirane with dimethylamine proceeds at the terminal position to afford the amino alcohol, 122. The amino alcohol is then converted to the halide (123). A displacement reaction with dimethylamine gives aminopromazine (124). ... 

The regioselective ring-opening of epoxides 34 (R1 = Me, vinyl, Ph etc.) with aminolead compounds R23 PbNEt2, prepared from lithium diethylamide and R23 PbBr, gives good yields of the amino alcohols 3567. 

The asymmetric epoxidation of allylic alcohols with cumene hydroperoxide or rerf-butyl hydroperoxide (TBHP) was first examined by using chiral amino alcohol-Mo complexes 45) and V complexes with chiral hydroxamic acid ligands (Scheme 20) 46). The highest optical yields were 33% with geraniol and 50% with 2-phenylcinnamyl alcohol. Combined use of VO(acac)2 and a hydroxamic acid derived from proline led to 80% optical yield with 2-phenylcinnamyl alcohol 47). 

A mixture of epoxides 483 obtained on oxidation of 482 with dimethyldioxirane, when exposed to ferric chloride provided, as the kinetically controlled product, the a-aldehyde 484, which without purification was reduced to the a-alcohol 485. The exclusive formation of 484 is believed to occur via the benzyl cation 486, generated by Lewis-acid opening of the oxirane ring, suffering a stereospecific kinetic 1,2-hydride shift The amino alcohol 487 obtained after sequential removal of O-benzyl and N-tosyl groups from 485, on treatment with triphenylphosphine and iodine in the presence of imidazole furnished the tetracyclic base 488, which was oxidised to the ketone 489. Trapping of the kinetically generated enolate of 489 as the silylether, followed by palladium diacetate oxidation yielded the enone 490. The derived... 

A novel approach to the asymmetric synthesis of epoxides, allylic alcohols, a-amino ketones, and a-amino aldehydes from carbonyl compounds through a,/i-epoxy sulfoxides using the optically active p-tolylsulfmyl group to induce chirality./. Org. Chem. 1989, 54, 3130-3136. 

The workers at Merck were able to go from start to finish in a single vessel. Base treatment of 22 + 23 led to attack at the epoxide end of 22 to give the anion 24. This is in equilibrium with the carbanion stabilised by Ar and CN and cyclises to an epoxide that gives a 15 85 mixture of the diastereoisomers 25 and 20. Reduction with borane gave a mixture of the amino alcohols... 

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