Asymmetric nitrone-vinyl sulfoxide cycloadditions: a highly enantioselective synthesis of (+)-sedridine

Louis, C.; Hootelé, Claude

doi:10.1016/0957-4166(95)00287-y

Cited by 39 publications

(7 citation statements)

References 18 publications

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“…99,100 Chiral vinyl sulfoxides have also been applied in 1,3-DC reactions. [101][102][103][104][105] These substrates were first used successfully in the 1,3-DC reaction by Koizumi et al in 1982. 103,104 In the 1,3-DC reaction of an (R)-p-tolyl vinyl sulfoxide and C,N-diphenylnitrone high selectivities were obtained.…”

Section: Chiral Alkenesmentioning

confidence: 99%

“…Louis and Hootele ´have studied the 1,3-DC reactions of vinyl sulfoxides 82 in the 1,3-DC reaction with the cyclic nitrone 57 (Scheme 10). 101,105 The reactions proceed with absolute exo selectivity, and, especially when the substituent at the (Z)-alkene is phenyl a high de of 96% is obtained. In the case where R ) Me (de ) 82%) the product 83 has been applied in the synthesis of the natural product (+)-sedridine 84.…”

Section: Chiral Alkenesmentioning

confidence: 99%

“…Brandi et al have used chiral vinylphosphine oxide derivatives as alkenes in 1,3-DC reactions with chiral nitrones. , This group also studied reactions of achiral nitrones with chiral vinylphosphine oxide derivatives. By using this type of substrates high endo / exo selectivities were obtained and in reactions involving optically pure vinylphosphine oxides diastereofacial selectivities of up to 42% de were obtained. , Chiral vinyl sulfoxides have also been applied in 1,3-DC reactions. − These substrates were first used successfully in the 1,3-DC reaction by Koizumi et al in 1982. , In the 1,3-DC reaction of an ( R )- p -tolyl vinyl sulfoxide and C,N- diphenylnitrone high selectivities were obtained. Louis and Hootelé have studied the 1,3-DC reactions of vinyl sulfoxides 82 in the 1,3-DC reaction with the cyclic nitrone 57 (Scheme ). , The reactions proceed with absolute exo selectivity, and, especially when the substituent at the ( Z )-alkene is phenyl a high de of 96% is obtained.…”

Section: 2 Chiral Alkenesmentioning

confidence: 99%

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Asymmetric 1,3-Dipolar Cycloaddition Reactions

1998

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Section: Chiral Alkenesmentioning

confidence: 99%

Section: Chiral Alkenesmentioning

confidence: 99%

Section: 2 Chiral Alkenesmentioning

confidence: 99%

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Asymmetric 1,3-Dipolar Cycloaddition Reactions

1998

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“…The latter approach was realized by Hootele who attached a chiral sulfoxide to the dipolarophile 181 (Scheme 43). 116 Reaction of 181 with nitrone 180 proceeded very cleanly to give the diastereomeric cycloadducts 182, 183 in a ratio of 94:6. Reductive cleavage of the N-O bond was achieved with Ni/Al and the optically pure alkaloid (+)sedridine (184) was isolated in 37% yield.…”

Section: Scheme 42mentioning

confidence: 99%

Stereoselective Synthesis of Piperidines

Laschat¹,

Dickner²

2000

Synthesis

385

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“…The piperidine alkaloid sedridine was isolated from Sedum acre in 1955, 6 several total syntheses were reported including those by Davis, 7 Murahashi, 8 Hootele, 9 Takahata, 10 and Litter. 11 The first four syntheses use chiral auxiliaries to obtain the chiral product.…”

mentioning

confidence: 99%

Total Synthesis of ent-Sedridine Using Proline-Catalyzed Asymmetric Addition as a Key Step

Itoh¹,

Nishimura²,

Nagata³

et al. 2006

Synlett

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A total synthesis of ent-sedridine is described. The development of a new method for the construction of the C-2 chiral center of the piperidine ring was achieved using a proline-catalyzed Mannich reaction. Reaction of 4-hydroxybutanal and p-anisidine to form an imine and subsequent addition of acetone gave the key chiral aliphatic precursor with high enantioselectivity.Piperidine alkaloids exist widely in nature and many of them have a chiral center at their C-2 position. 1 However, in most cases, the amount of these alkaloids in biological systems is minute and it is therefore important to develop general methods to obtain these compounds, which have possible bioactivity. 2In the course of our study into the synthesis of indole alkaloids, 3 we have found that a proline-catalyzed asymmetric Mannich reaction 4 serves as a highly effective tool for the construction of a chiral center which is crucial for asymmetric synthesis. 5 Based on previous work, we have tried to apply this catalytic system to the synthesis of piperidine alkaloids and have found that a total synthesis of ent-sedridine could be achieved using the proline-catalyzed Mannich reaction as a key step. This paper describes these results.The piperidine alkaloid sedridine was isolated from Sedum acre in 1955, 6 several total syntheses were reported including those by Davis, 7 Murahashi, 8 Hootele, 9 Takahata, 10 and Litter. 11 The first four syntheses use chiral auxiliaries to obtain the chiral product. Litter and coworkers used the only synthesis involving a catalytic asymmetric transformation. In this paper, catalytic hydrogenation of a ketone was adopted as the asymmetric process, the ketoester intermediate was then reduced to the corresponding hydroxyester using Ru-BINAP as the catalyst under H 2 (200 psi). We thought that there were still drawbacks in the previous syntheses, namely the need for equimolar amounts of chiral sources or harsh reaction conditions.We investigated a new method for the construction of the C-2 chiral center of the piperidine ring, using a prolinecatalyzed Mannich reaction. List and co-workers reported a catalytic asymmetric Mannich reaction using imines, which were formed in situ by the reaction of an aromatic aldehyde and an amine, and enamines derived from (S)-proline and methyl ketones to give b-aminoketones in a highly enantioselective manner. 4 The application of the reaction to aldehydes was, however, seldom reported. 12Retrosynthesis for ent-sedridine is shown in Scheme 1. Sedridine (1) was to be obtained from an aliphatic precursor 2 by the Mitsunobu reaction. Compound 2 could be synthesized from the reaction of an imine 3 (formed by the reaction of 4-hydroxybutanal and p-anisidine) with an enamine 4 derived from (S)-proline and acetone.

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Asymmetric nitrone-vinyl sulfoxide cycloadditions: a highly enantioselective synthesis of (+)-sedridine

Cited by 39 publications

References 18 publications

Asymmetric 1,3-Dipolar Cycloaddition Reactions

Asymmetric 1,3-Dipolar Cycloaddition Reactions

Stereoselective Synthesis of Piperidines

Total Synthesis of ent-Sedridine Using Proline-Catalyzed Asymmetric Addition as a Key Step

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Asymmetric nitrone-vinyl sulfoxide cycloadditions: a highly enantioselective synthesis of (+)-sedridine

Cited by 39 publications

References 18 publications

Asymmetric 1,3-Dipolar Cycloaddition Reactions

Asymmetric 1,3-Dipolar Cycloaddition Reactions

Stereoselective Synthesis of Piperidines

Total Synthesis of ent-Sedridine Using Proline-Catalyzed Asymmetric ­Addition as a Key Step

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Total Synthesis of ent-Sedridine Using Proline-Catalyzed Asymmetric Addition as a Key Step