Diastereo- and enantio-selective synthesis of dihydro- and tetrahydro-pyrimidines. A new strategy for the asymmetric synthesis of β-amino ketones and γ-amino alcohols

Abstract

Chiral 1,2-dihydro-(3) and 1,2,3,6-tetrahydro-pyrimidines (4) have been synthesized b y reaction of 3-aminoalk-2-enimines (1) w i t h chiral aldehydes, the structure of (4) being confirmed b y an X-ray crystal structure determination of a reduction product; a new strategy for the asymmetric synthesis of 6-amino ketones (2) and y-amino alcohols (6) with t w o or three chiral centres is described.

Asymmetric synthesis of 1,3-aminoketals

“…These synthons can, in fact, be obtained from chiral compounds (by reduction and acidic hydrolysis of 1,3-diimines, 6 by ring opening of b-lactams, 7 or by functional modification of b-aminocarbonyls 8 ) or, most frequently, by an asymmetric Mannich-type reaction. 9 During this reaction, asymmetry can be induced either by using preformed chiral reagents 10 or by the use of a chiral catalyst.…”

Synthesis and structural study of a new series of 2‐methylsulfanyl‐tetrahydropyrimidines from β‐alkoxyvinyl trihalomethyl ketones

“…1 H-and 13 C-NMR spectra were acquired on a Bruker DPX 400 spectrometer ( 1 H at 400.13 MHz and 13 C at 100.62 MHz) in DMSO-d 6 or CDCl 3 , using TMS as the internal reference.…”

“…Strategies that have been developed to obtain the tetrahydropyrimidine ring include: i) dialkylation of both nitrogen atoms of the pyrimidine ring [1] or one of the backbone carbons [2], ii) reduction of the parent pyrimidine [3], iii) condensation of 1,5-diamines with cyanogen bromide or aldehydes [4][5][6][7], iv) reaction of , -unsaturated carbonyl compounds or acrylates with dinucleophiles of the N-C-N type [8][9][10][11][12], and v) addition reactions to pyrimidines [13][14][15]. An interesting method, based on a triad of reaction components such as 3-oxo esters, 1,3-diketones or -alkoxyvinyl trichloromethyl ketones with benzaldehyde and (thio)urea, resulting in the formation of a series of 4-fluoroalkyl [16] and 4-trichloromethyl [17] substituted tetrahydropyrimidines, has been reported.…”

Diastereospecific Synthesis of Enantiomerically Pure Polysubstituted Azetidines from 1,3-Amino Alcohols with Three Chiral Centers

“…Thus, we have described a diastereoselective synthesis of these compounds by reduction of 4-amino-1-azadienes and related systems . A diastereo- and enantioselective preparation of 1,3-amino alcohols 5 was carried out from 4-amino-1-azadienes 1 via the corresponding dihydro- and tetrahydropyrimidines 2 and 3 using an aldehyde as chiral auxiliary (Scheme ); β-amino ketones 4 obtained from tetrahydropyrimidines 3 by hydrolysis were submitted to reduction with complex metal hydrides leading to 5 …”

“…7 A diastereo-and enantioselective preparation of 1,3-amino alcohols 5 was carried out from 4-amino-1-azadienes 1 via the corresponding dihydro-and tetrahydropyrimidines 2 and 3 using an aldehyde as chiral auxiliary (Scheme 1); β-amino ketones 4 obtained from tetrahydropyrimidines 3 by hydrolysis were submitted to reduction with complex metal hydrides leading to 5. 8 More recently, we reported the synthesis of all isomers of the N-terminal amino acid of the antibiotics nikkomycin B and B x following the synthetic plan outlined here. 9 As part of our continuing interest in the chemistry of 1,3-amino alcohols we now report the synthesis of optically active 2,3,4-substituted azetidines from 1,3-amino alcohols containing three chiral centers.…”