A Stereoselective Synthesis of Five‐ and Six‐Membered Cyclic β‐Amino Acids

Perlmutter, Patrick; Rose, Mark L; Vounatsos, Filisaty

doi:10.1002/ejoc.200390118

Cited by 26 publications

(15 citation statements)

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“…Complete descriptions of all experiments relating to the first section of this paper, namely thioenolate additions to chiral imines, as well as full experimental introduction, have already been reported [8].…”

Section: Methodsmentioning

confidence: 99%

“…The overall strategy follows the "NARC" sequence strategy we have developed for preparing complex cyclic structures, where the NA stands for nucleophilic addition and the RC represents ring construction [7]. In the first instance the chiral auxiliary (X*) is attached to the imine ( Figure 1, Equation (a)) yields products of general structure III which is discussed in this Introduction [8]. In the second the chiral auxiliary (Y*) is attached to the enolate ( Figure 1, Equation (b)).…”

Section: Introductionmentioning

confidence: 99%

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The asymmetric imino-aldol approach to the enantioselective synthesis of β-amino acids

et al. 2003

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SummaryTwo approaches, based on imino-aldol additions, to the asymmetric synthesis of cyclic /~-amino acids are reported. In each case a chiral auxiliary was employed attached either to the enolate or to the imine. The relative efficacy of these two synthetic methods is also briefly compared with the former still the preferred route as the latter is currently limited to the preparation of N-sulfonyl fl-amino acids.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The asymmetric imino-aldol approach to the enantioselective synthesis of β-amino acids

et al. 2003

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“…An advantage of this procedure is that it furnishes unsaturated carbocyclic b-amino acids, whose olefinic bond may be further functionalized. The stereocenters of the starting lactam remain unaffected during the process, resulting stereoselectively in trans-b-aminocyclopentanecarboxylic and trans-b-aminocyclohexanecarboxylic acid hydrochlorides 36a,b [14]. The first step, stereoselective addition of the chiral lithium amide, generating the two C stereocenters, was followed by synthesis of dieno amino esters 29a,b and 31 in several steps.…”

Section: Synthesis Of Carbocyclic B-amino Acids By Ring-closing Metatmentioning

confidence: 99%

Synthesis of Carbocyclic β‐Amino Acids

Kiss

Forró

Fülöp

2009

Amino Acids, Peptides and Proteins in Organic Chemistry

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j367 acids was reviewed by our group in 2001 [1]; the present chapter highlights the chemistry of these compounds published since 2000, with the aim of offering the reader an insight into the most recent developments in this field. Synthesis of Carbocyclic b-Amino AcidsOwing to their significance, a number of methods have been developed for the synthesis of these conformationally restricted molecules in racemic and enantiomerically pure form. The largest groups of carbocyclic b-amino acids and the most intensively investigated are the fiveand six-membered derivatives. One main method of preparation consists of the amidation of 1,2-dicarboxylic anhydrides 4, followed by Hoffmann rearrangement of the resulting amide 5 to amino acid 7. The same starting material, the meso anhydride 4, undergoes partial hydrolysis, followed by the Curtius rearrangement, to give 2-aminocyclohexanecarboxylic acid 7 (Scheme 8.1) ([1] and references cited therein).A widely used method for the synthesis of carbocyclic b-amino acids is the transformation of cycloalkenes via the corresponding bicyclic b-lactams. The 1,2dipolar cycloaddition of chlorosulfonyl isocyanate (CSI) to cycloalkenes 8 led regioselectively to the cycloalkane-fused b-lactams 10, whose acidic hydrolysis resulted in lactam ring opening and formation of the carbocyclic b-amino acid hydrochlorides 11 (Scheme 8.2) ([1] and references cited therein). O O O NH 4 OH COOH CONH 2 1. ROH 2. HO 3. H COOR COOH Curtius degradation COOH NH 2 Hoffmann degradation NaOH, Br 2 1. SOCl 2 2. NaN 3 Dowex 4 5 6 7 Scheme 8.1 Synthesis of carbocyclic b-amino acids by Curtius and Hoffmann rearrangements. CSI NSO 2 Cl O H 2 O NH O HCl, RT COOH NH 2 HCl 8 9 10 11 Scheme 8.2 Synthesis of carbocyclic b-amino acids from b-lactams. 368j 8 Synthesis of Carbocyclic b-Amino Acids 15 16 18 17 16:17:18 = 95.5:1.7:2.8 KOtBu, tBuOH ∆, 3hScheme 8.4 Synthesis of 3-methylcispentacin derivatives by conjugate addition. Synthesis of Carbocyclic b-Amino Acids j369To prepare 3-methyltranspentacin, aminocarboxylate 17 was first obtained in a larger quantity from diastereoisomer 16 by epimerization on treatment with KOtBu in tBuOH; this afforded 17 in quantitative yield and a diastereomeric excess of 99%. N-Deprotection of 17, followed by ester hydrolysis, gave the desired 3-methyltranspentacin in 97% e.e. [9].By using this conjugate addition methodology, Davies et al. also prepared 5-substituted derivatives of cispentacin. The addition of lithium amide (S)-13 to 5-isopropyl-, 5-phenyl-, and 5-tert-butylcyclopentenecarboxylates proceeded with a high degree of selectivity, the major derivatives formed having the amine anti to the 5-alkyl group. N-Deprotection by hydrogenolysis, subsequent acid hydrolysis of the ester, and ion-exchange chromatography furnished 5-substituted cispentacin derivatives in 98% e.e. [10].The asymmetric synthesis of a series of functionalized derivatives was achieved by using amine conjugate addition processes. Four stereoisomers of 2-amino-5carboxymethylcyclopentanecarboxylate were prepared ...

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“…Particularly interesting is the report of Perlmutter et al [175], who describe the diastereoselective condensation under Lewis acid conditions (SnCl 4 ) of pyridyl thioester and an enantiopure imine to yield a diastereomeric mixture of b-lactam derivatives 110, which were separated by chromatography. Treatment of the blactams with chlorotrimethylsilane in the presence of benzyl alcohol gave the desired metathesis substrates, which were subjected to Grubbs catalyst under high-dilution conditions to afford the desired cyclic b-amino esters (Scheme 7.109).…”

Section: Synthesis Of B-amino Acids Via Radical Reactionsmentioning

confidence: 99%