A new method for the enantioselective synthesis of N-Boc-α,α-disubstituted α-amino acids (original) (raw)
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A new method for the enantioselective synthesis of N-Boc-a,a-disubstituted a-amino acids
Tetrahedron, 2001
Boc-a,a-disubstituted a-amino acids has been developed. The starting materials are diastereomerically pure 3,3-disubstituted allyl alcohols, prepared by DIBAL-H reduction of the corresponding unsaturated esters derived from carbocupration of an acetylenic ester or from Wadsworth±Emmons ole®nation of a ketone. Sharpless epoxidation of the allylic alcohols provided enantiomerically enriched epoxy alcohols that were submitted to nucleophilic ring-opening under Crotti's conditions (N 3 Na/LiClO 4) to give 3-azido-1,2-diols. Hydrogenation and in situ protection provided the N-Boc-3-amino-1,2-diols that were oxidatively cleaved to the a,a-disubstituted N-Boc-a-amino acids. Protected a-methyl-a-phenylglycine and a-methylisoleucine have been prepared by this methodology.
Tetrahedron: Asymmetry, 1999
A versatile, non-alkylative enantioselective synthesis of unsaturated α-amino acids based on the Sharpless asymmetric epoxidation has been developed. Enantiomerically enriched trans epoxy alcohols bearing unsaturated substituents were prepared and submitted to regio-and stereospecific ring-opening with p-methoxybenzylamine as a nucleophile, leading to anti-3-(p-methoxybenzylamino)-1,2-diols which were further protected by reaction with Boc 2 O. The 1,2-diol fragment was then oxidatively cleaved by a sequential treatment with sodium periodate and sodium chlorite to afford the corresponding amino acid. Using this methodology, doubly N-protected (pmethoxybenzyl and Boc) allyl glycine, 3-butenyl glycine and 4-pentenyl glycine have been prepared in three synthetic steps from the corresponding allyl alcohols. As a demonstration of the orthogonal nature of the nitrogen protection, both protecting groups have been selectively removed from the fully protected amino ester.
Synthesis of enantiomerically enriched β,γ-unsaturated-α-amino acids
Tetrahedron, 2001
AbstractÐA variety of enantiomerically enriched b,g-unsaturated-a-amino acids are synthesized by ole®nation of a Cbz-protected serine aldehyde equivalent, readily prepared from serine. A cyclic ortho ester protecting group is employed to minimize racemization. The deprotected amino acids are obtained in good yield, ranging from 70±95% ee, with double-bond geometry determined by the type of Wittig reagent used. Isotopically labeled side chains are readily introduced by this procedure, and free g-13 C-vinylglycine was prepared in 44% yield from the protected serine aldehyde synthon. q
Enolboration of Conjugated Ketones and Synthesis of β-Amino Alcohols and Boronated α-Amino Acids
ChemInform, 2003
Enolization-aldolization of conjugated ketones, enantioselective synthesis of benzofuryl β-amino alcohols, and synthesis of p-dihydroxyborylphenylalanine (BPA) and its analogs are described. Aldolization of benzaldehyde with lithium dienolates derived from unhindered conjugated cyclohexenones favored anti selectivity, whereas syn selectivity was favored for hindered cyclohexenones. Anti-aldols were preferentially formed from dienolborinates derived from conjugated cyklohexenones, however, competing aldolization at the 2-position was observed for hindered ketones. Benzofuryl β-amino alcohols were prepared using as a key step the enantioselective reduction of the corresponding α-bromoacetylbenzofurans with (-)-B-chlorodiisopinocampheylborane. Ionic liquids were used as solvents for the synthesis of BPA by the Suzuki cross-coupling reaction. The reaction time is short, and a solution of the catalyst in the ionic liquid can be recycled.
International Journal of Chemical Engineering and Applications, 2016
An efficient method for the asymmetric synthesis of enantiomerically enriched derivatives of (S)-propargylglycine by С-alkylation of Ni II-complex of Schiff's bases of propargylglycine and chiral auxiliary (S)-2-N-[N'-(benzylprolyl) amino] benzophenone with benzyl bromide and its derivatives (de 85-90 %) has been developed. This resulted in synthesis of new enantiomerically enriched α-amino acids containing acetylenic bond in the side chain (ee >95%).
Angewandte Chemie International Edition, 2021
For the first time we have been able to employ enantiopure 1,2-amino alcohols derived from abundant amino acids in CÀC bond-forming hydrogen-borrowing alkylation reactions. These reactions are facilitated by the use of the aryl ketone Ph*COMe. Racemisation of the amine stereocentre during alkylation can be prevented by the use of substoichiometric base and protection of the nitrogen with a sterically hindered triphenylmethane (trityl) or benzyl group. The Ph* and trityl groups are readily cleaved in one pot to give gaminobutyric acid (GABA) products as their HCl salts without further purification. Both steps may be performed in sequence without isolation of the hydrogen-borrowing intermediate, removing the need for column chromatography. Scheme 1. A) Previous work, B) proposed hydrogen-borrowing reaction of 1,2-amino alcohols with Ph* methyl ketone.
New approach to exclusive formation of both enantiomers of β-amino acid derivatives
Tetrahedron, 2008
A highly selective two-step approach to chiral b-amino esters via the hydride reductive amination of chiral allenes is reported. b-Enamino esters were obtained from the nucleophilic addition of amines to 2,3-allenoates bearing a chiral auxiliary. The reduction of the (1R)-(À)-10-phenylsulfonylisobornyl b-enamino esters gave the corresponding b-amino esters with S configuration whereas the reduction of the (1S)-(þ)-10-phenylsulfonylisobornyl b-enamino esters led to b-amino esters with R configuration.
Direct Stereoselective Synthesis of Enantiomerically Pure anti-β-Amino Alcohols
The Journal of Organic Chemistry, 2014
Enantiomerically pure anti-β-amino alcohols were synthesized from optically pure α-(N,N-dibenzylamino)benzyl esters, derived from α-amino acids, by the sequential reduction to aldehyde with DIBAL-H at −78°C and subsequent in situ addition of Grignard reagents. Besides anti-β-amino alcohols, anti-2-amino-1,3diols and anti-3-amino-1,4-diols were obtained in good yields (60− 95%) and excellent stereoselectivity (de > 95%). Our technique is compatible with free hydroxyl groups present in the substrate. To demonstrate the versatility of the method, spisulosine and sphinganine were synthesized in two steps from the appropriate N,N-dibenzyl-L-aminobenzyl ester in 42% and 45% yield, respectively.