General method of diastereo- and enantioselective synthesis of β-hydroxy-α-amino acids by condensation of aldehydes and ketones with glycine

Abstract

mL and DMF and saturated with methylamine gas at 0 OC. The vessel was sealed and agitated for 1 day. The polymer was washed successively in dioxane, ethanol, 2 N NaOH/i-PrOH (l:l), water (until eluate neutral), ethanol, and ether. After drying in vacuo, the polymer (3.7 g/3.8 mequiv of amino groups/l g of dry weight) was suspended in a mixture of water (1.5 mL), ethanol (0.5 mL), triethylamine (7 mL), and 4chloropyridine hydrochloride (4.7 g) in a glass pressure vessel, sealed and heated for 4 days at 140 OC. The polymer was washed as before, and unreacted amino groups were blocked by acetylation (acetic anhydride in CH2C12, then base wash). The washed DMAP polymer was dried at 150 OC in vacuo until constant weight. Incorporation of pyridine groups was determined by potentiometric chloride titration of the hydrochloride salt bound to the polymer: 2.53 mequiv/g compared to 3.15 mequiv/g prior to acetylation.Polymeric l-Acyl-4-(diaUtylamino)pyridinium Chlorides. In a typical experiment, the anhydrous 4-(dialkylamino)pyridine polymer was swelled in methylene chloride (freshly distilled from P205 under argon) and treated with excess benzoyl chloride at 0 OC. The polymer was filtered and washed with methylene chloride under anhydrous conditions until the washings contained negligible amounts of benzoyl chloride-by the silver nitrate test in alcohol (less than 0.1% of total pyridine groups as indicated by GC). The polymer was dried under vacuum at room temperature and was stable at -10 OC for several months. After treatment with a primary (e.g., benzyl) amine in methylene chloride, a pure amide was recovered by filtration and acid/base wash. The amount of amide corresponded to 0.8 mequiv/g of acyl substitution on the polymer. Anhydrous manipulation as above and those involving transfer between two polymers were most conveniently carried out by using a circulating system described in Figure 1, containing Teflon columns (1-4-(10) Warshawsky, A,; Deshe, A.; Rossey, G.; Patchornik, A. React. Polym. 1984, 2, 301.mL volume) joined to the solvent distillation apparatus, waste, and vacuum pump via Teflon tubing.In summary, we have shown for the first time the possibility to perform highly efficient condensation reactions, by transferring polymerbound electrophiles (Le., active esters) via a mediator (shadchan) to polymer-bound nucleophiles (i.e., amines). We have also shown the possibility of on-line monitoring which is relevant for automation.The mediator methodology developed here is believed not to be limited to acylation and related processes but to be expandable to other chemical processes that involve the creation of activated intermediates. These possibilities are currently under investigation. Acknowledgment. We thank the Etta P. Schiff Trust and the Bantrell Fund for financial support. This work is dedicated to Prof. Arieh Berger on t h e 10th anniversary of his death.

Diastereoselective Michael reaction of chiral nickel(II) glycinate with nitroalkenes for asymmetric synthesis of β-substituted α,γ-diaminobutyric acid derivatives in water

“…However, all these reactions were performed in organic solvents. In this report, we have focused on nickel(II) glycinate, which is important for asymmetric synthesis of chiral amino acids (Belokon et al 1985;Cai et al 2004;Soloshonok et al 2001;Taylor et al 2004;Wang et al 2008). While significant progress has been made in the use of chiral nickel(II) glycinate in asymmetric synthesis of enantiopure amino acids, the development of diastereoselective Michael reactions using nickel(II) glycinate has proven to be a challenging task (Cai et al 2001;Soloshonok et al 2000Soloshonok et al , 2001.…”

From Carbon-11-Labeled Amino Acids to Peptides in Positron Emission Tomography: the Synthesis and Clinical Application

“…The methodology has been introduced in organic and organometallic chemistry by Belokon in 1985 [63]. These chiral nickel complexes proved to be highly versatile and allowed a very high level of stereocontrolled C-11 alkylation reactions due to high acidity of the α-hydrogen.…”

Asymmetric Synthesis of (S)-2-Amino-3-(1-naphthyl)propanoic Acid via Chiral Nickel Complex. Crystal Structure, Circular Dichroism, 1H and 13C NMR Spectra of the Complex

“…A synthetic pathway employing chiral nickel complexes prepared from α-amino acids and chiral auxiliary BPB ((S)-N-(2-benzoylphenyl)-N′-benzylprolinamide) is an exception. After preparation of desired α-amino acid, enantiomerically pure BPB·HCl is regenerated in high yield (>90%) 3 . The complexes provide easy generation of intermediate carbanion due to high acidity of α-hydrogen of an amino acid fragment (pK a ≥ 19) 4 .…”