Chiral heterocyclic β-enamino esters: convenient synthesis and diastereoselective reduction

Calvet, Sandrine; David, Olivier; Vanucci-Bacqué, Corinne; Fargeau-Bellassoued, Marie-Claude; Lhommet, G.

doi:10.1016/s0040-4020(03)00980-3

Cited by 33 publications

(10 citation statements)

References 16 publications

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“…29 To 0.216 g (1 mmol) of isobutyl 7-chlorohept-2-ynoate dissolved in 5 mL of dry acetonitrile was added 2 equiv of iso-propyl amine in a screw-capped vial at room temperature. The mixture was stirred for 8 h at room temperature and then the product was separated on silica gel column (90% petroleum ether/10% ethyl acetate), and analyzed by GC/MS, elemental analysis, and NMR spectroscopy.…”

Section: Generalmentioning

confidence: 99%

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Comparison of amine-induced cyclization of 6-chloro-1-hexynylphosphonate and isobutyl 7-chlorohept-2-ynoate

et al. 2009

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Section: Generalmentioning

confidence: 99%

“…27,28 Cyclic chiral b-enamine esters have been prepared from u-halogeno b-keto esters with chiral amines. 9,29,30,31 The addition of amines to 1-alkynylphosphonates 32 leads to 2-amino-1-alkenylphosphonates. 33 The latter are useful intermediates in organic synthesis for the preparation of other phosphorus-containing compounds.…”

Section: Introductionmentioning

confidence: 99%

Comparison of amine-induced cyclization of 6-chloro-1-hexynylphosphonate and isobutyl 7-chlorohept-2-ynoate

et al. 2009

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“…21) [44][45][46]. The hydrogenation of the N -substituted β-aminoesters (with (1S)-phenylethylamine or (1S)-phenylglycinol) was highly stereoselective over Pd(OH) 2 /C or PtO 2 .…”

Section: References See Page 3661mentioning

confidence: 99%

Diastereoselective Catalysis

Бессон

Pinel

2008

Handbook of Heterogeneous Catalysis

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IntroductionA reaction is referred to as stereoselective when a substrate S, which may yield a series of stereoisomer products (P 1 , P 2 , . . . P n ) gives preferentially -or even exclusively -one of these. Today, the preparation of stereoisomeric compounds is generating tremendous academic and industrial interest. Especially, the synthesis of enantiopure chiral compounds is becoming increasingly important in the production of pharmaceuticals, agrochemicals, fragrances, and flavor substances. Among the different methods used to prepare pure enantiomers, asymmetric catalysis plays an important role, particularly hydrogenation. Currently, two types of asymmetric hydrogenation with solid catalysts are utilized, namely enantioselective and diastereoselective synthesis.In enantioselective hydrogenation, one enantiomer of a chiral product is formed preferentially from a prochiral precursor, the stereoselectivity being induced by a chiral catalyst. Immobilization of very selective metal-ligand complexes and modification of active metals by an adsorbed chiral organic molecule (chiral modifier) have been extensively studied [1]. In some cases, high enantioselectivities approaching 98% enantiomeric excess (e.e.) have been obtained with modified supported metal catalysts. The numerous investigations devoted to the understanding of the mechanism have been summarized in several reviews [1][2][3][4][5]. The most effective catalysts are Ni-tartaric acid, Pt-cinchona, Pd-cinchona and, to a lesser extent, Rh-cinchona systems. The field of reaction types is still limited to a narrow range of asymmetric hydrogenations.The other frequently used catalytic strategy for the synthesis of pure enantiomers is based on diastereoselective hydrogenation. This involves the selective formation of one diastereoisomer by creating a new stereogenic center in a chiral molecule. In this approach, the reaction consists of three simple steps. First, a covalent bond between the prochiral substrate and a chiral moiety (chiral auxiliary) is formed. Then, the diastereoselective hydrogenation is performed over various noble metal catalysts, leading stereoselectively to a new chiral center. This step does not require a chiral catalyst, but the stereogenic center in the chiral auxiliary is able to induce the stereoselectivity. The desired molecule can finally be obtained by selective cleavage of the chiral auxiliary from the product which can be recycled.

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“…To evaluate the scope of our new MCR, we carried out the reactions using various b-keto esters (R 2 = OR) and bdiketones (R 2 = alkyl, phenyl) 2a-j whose R 3 substituents were either simple or functionalized alkyl groups or, alternatively, a phenyl moiety ( Table 1). The corresponding compounds were commercially available, except for compounds 2d 9 and 2f 10 that were prepared by condensation of the dianion of methyl acetoacetate with 1-bromo-3-chloropropane or 2-(2-bromoethyl)-1,3-dioxolane, respectively.…”

Section: Figurementioning

confidence: 99%

“…From 2d9 (124 mg, 0.65 mmol), (S)-2-phenylglycinol (80 mg, 0.58 mmol), acrolein (45 mL, 0.65 mmol) and 4-Å MS (5.8 g) in refluxing toluene (23 mL) for 24 h was obtained 1d (83 mg, 41%) as an 80:20 inseparable mixture of two diastereomers.…”

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confidence: 99%

Convenient One-Pot Synthesis of Chiral Tetrahydropyridines via a Multicomponent Reaction

Noël¹,

Fargeau-Bellassoued²,

Vanucci-Bacqué³

et al. 2008

Synthesis

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The multicomponent condensation of various b-dicarbonyl compounds, acrolein and (S)-2-phenylglycinol was found to provide a one-pot access to chiral 6-carbonyl-3-phenyl-2,3,8,8a-tetrahydro-7H-[1,3]oxazolo[3,2-a]pyridines. The value of this methodology is illustrated by the short and efficient synthesis of (-)-lupinine.Substituted tetrahydropyridine intermediates have proved to be useful for the preparation of various natural products such as matrine, 1 cytisine 2 and tashiromine. 3 For our part, we have recently reported the preparation of chiral 6-carbonyl-3-phenyl-2,3,8,8a-tetrahydro-7H-[1,3]oxazolo[3,2-a]pyridine derivatives 1 whose diastereoselective controlled reduction enabled us to prepare enantiopure 'all cis' 2,6-and 2,3,6-substituted b-amino carbonyl piperidines. 4 This approach allowed us to achieve the efficient total synthesis of a 2,6-disubstituted 3-hydroxypiperidine, (-)-deoxocassine. 4 Compounds 1 were prepared according to a two-step sequence 5 featuring a Michael reaction of symmetrical b-diketones or b-keto esters 2 with a,b-unsaturated carbonyl compounds 3 (in particular, acrolein and methyl vinyl ketone), followed by the condensation of a chiral amine, (S)-2-phenylglycinol (5), with the resulting tricarbonyl compounds 4 (Scheme 1, Route a). Following these results, we envisioned an alternative strategy allowing the preparation of these complex compounds via a one-pot multicomponent reaction (MCR).Indeed, MCRs have recently emerged as a powerful tool in organic synthesis due to their advantages such as time and cost savings, atom economy and environmental friendliness. Recent studies on MCRs between b-dicarbonyl derivatives, a,b-unsaturated compounds and functionalized amines 6,7 have prompted us to report our results on the preparation of target compounds 1 via a three-component reaction involving compounds 2, 3 and (S)-2-phenylglycinol (5) (Scheme 1, Route b). The value of the resulting chiral tetrahydropyridines as precursors of natural products will be illustrated by the total enantioselective synthesis of the quinolizidine alkaloid (-)-lupinine (6) (Figure 1). Scheme 1 Figure 1In a preliminary study, we found that reactions with various a,b-unsaturated carbonyl compounds 3 were only efficient in the case of acrolein (3a, R 1 = H). 8 Therefore, we decided to focus our study on the preparation of tetrahydrooxazolopyridines 1 bearing an angular hydrogen atom at C-8a (R 1 = H).To evaluate the scope of our new MCR, we carried out the reactions using various b-keto esters (R 2 = OR) and bdiketones (R 2 = alkyl, phenyl) 2a-j whose R 3 substituents were either simple or functionalized alkyl groups or, alternatively, a phenyl moiety (Table 1). The corresponding compounds were commercially available, except for compounds 2d 9 and 2f 10 that were prepared by condensation of the dianion of methyl acetoacetate with 1-bromo-3-chloropropane or 2-(2-bromoethyl)-1,3-dioxolane, respectively.We first investigated the condensation of b-keto ester 2a (R 2 = OMe, R 3 = Me), acrolein (3a) and (S)-2-phenylglyci...

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Chiral heterocyclic β-enamino esters: convenient synthesis and diastereoselective reduction

Cited by 33 publications

References 16 publications

Comparison of amine-induced cyclization of 6-chloro-1-hexynylphosphonate and isobutyl 7-chlorohept-2-ynoate

Comparison of amine-induced cyclization of 6-chloro-1-hexynylphosphonate and isobutyl 7-chlorohept-2-ynoate

Diastereoselective Catalysis

Convenient One-Pot Synthesis of Chiral Tetrahydropyridines via a Multicomponent Reaction

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