Diasteroselective Cyclizations with Enantiopure Malonaldehyde Monocycloacetals (original) (raw)
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The Journal of Organic Chemistry, 1997
The factors which effect the stereoselective formation of trans-1-alkyl-2-benzyl-3-(alkoxycarbonyl)-1,2,3,4-tetrahydro-carbolines and trans-3-(alkoxycarbonyl)-1-alkyl-2-(diphenylmethyl)-1,2,3,4tetrahydro-carbolines by the Pictet-Spengler cyclization were examined by heating tryptophan derivatives with aldehydes of varied steric bulk under aprotic and acidic conditions, followed by determination of the ratio of cis to trans diastereomers so formed. The presence of a benzyl group at the N b-nitrogen atom alters the diastereochemical outcome of this condensation to provide 100% trans stereoselectivity when the cyclization is carried out with cyclohexanecarboxaldehyde. Furthermore, when N b-(diphenylmethyl)tryptophan isopropyl ester was condensed with aldehydes of any size, trans diastereomers are formed with 100% stereoselectively. The trans N b-substituted diastereomers are thermodynamically more stable than their cis congeners as shown by equilibration experiments in TFA. Conversion of the cis diastereomers into the more stable trans diastereomers is believed to occur under acidic conditions by cleavage of the carbon (C-1)-nitrogen (N-2) bond with complete retention of configuration at the C-3 stereocenter. Evidence from deuterium exchange experiments as well as optical rotations support this model for epimerization. In addition, when cis diastereomer 66a was allowed to stir in CF 3 COOD, the trans isomer 66b was isolated in 90% yield, while treatment of cis 66a with CF 3 COOH/NaBH 4 provided a mixture of the ring cleaved [scission across C(1)-N(2) bond] product 67 and the trans isomer 66b. Treatment of 66b (control experiment) with NaBH 4 /CF 3 COOH under the same conditions returned only starting trans 66b in excellent yield. The Pictet-Spengler reaction of substrates with sufficiently large substituents, followed by treatment with acid, permits the 100% enantiospecific formation of trans-1,3disubstituted-1,2,3,4-tetrahydro-carbolines for alkaloid total synthesis.
Diastereocontrolled multicomponent pathway to 3,4-heterocycle-annulated tetrahydro-β-carbolines
Tetrahedron: Asymmetry, 2005
A diastereoselective synthesis, using the Yonemitsu-type trimolecular condensation as the key step, has been used for the preparation of 3,4-heterocycle(furanone-, pyrrolidinone-and pyranone-) annulated tetrahydro-b-carbolines. The chirality of D D-glyceraldehyde or that of the GarnerÕs aldehyde ensured a high and predictable diastereocontrol of the additional newly created stereocentres.
Journal of the Brazilian Chemical Society, 2013
Uma nova síntese dos enantiômeros (-)-(R)-e (+)-(S)-angustureina, assim como do racemato (±)-angustureina, a partir de um b-amino éster racêmico controlado por resolução cinética enzimática, é descrita. Esta estratégia permitiu, incorporar tanto o esqueleto básico como controlar o único estereocentro no carbono 2 de ambos enantiômeros. A sequência em cinco etapas a partir dos b-amino éster e o carboxilato de sódio quirais para a síntese de ambos os alcalóides foi feita com um rendimento global de 80 e 44%, respectivamente, e excelentes excessos enantiomericos (95 e 96%, respectivamente) e sem nenhuma proteção de grupos funcionais em todas as etapas. The present study describes a new synthesis of (-)-(R)-and (+)-(S)-angustureine enantiomers, as well as of racemate (±)-angustureine, from a racemic b-amino ester controlled by kinetic enzymatic resolution. This strategy allowed to incorporate the basic skeleton, as well as to control the single stereocenter at carbon 2 in both enantiomers. The sequence of five steps starting from the chiral b-amino ester and sodium carboxylate for the synthesis of both alkaloids achieved overall yields of 80 and 44%, respectively, and produced excellent enantiomeric excesses (95 and 96%, respectively) with no protection of functional groups in any of the steps.
Current Organic Synthesis, 2015
The synthesis of high optical purity chiral compounds is of current importance in organic and organometallic areas of the chemistry with further boost. Chiral compounds are important because of wide use in many areas such as pharmacy and food industry, etc. Reagents, catalysts or chiral auxiliaries that can control the stereochemistry of the products are required for the synthesis of chiral compounds. Furthermore, the reagents used must be able to be recycled. In recent decades, Ephedra derivative compounds have been widely used as catalyst chiral ligands or chiral inductors in asymmetric synthesis. To our knowledge, no review about Ephedra derivative compounds as chiral auxiliaries used with organometallics in alkylation reactions to carbonyl compounds, has been published. In this paper, the use of N-substituted and N-disubstituted ephedra compounds as chiral auxiliary ligands in alkylation, alkenylation and alquinilation reactions of carbonyl and imine compounds is summarized.
Enantioselective Organocatalytic Synthesis of 5 and 6 Membered Heterocycles
Current Organic Chemistry, 2011
An asymmetric organocatalytic cascade reaction which can afford a series of oxazolidine derivatives has been developed. The one-pot reaction reported here can produce an oxazolidine derivative in a highly enantioselective manner and good yield with good to excellent diastereomeric ratio.