142572-48-3Relevant academic research and scientific papers
A convenient new route to piperidines, pyrrolizidines, indolizidines, and quinolizidines by cyclization of acetylenic sulfones with β- and γ-chloroamines. Enantioselective total synthesis of indolizidines (-)-167B, (-)-209D, (-)-209B, and (-)-207A
Back, Thomas G.,Nakajima, Katsumasa
, p. 4543 - 4552 (2007/10/03)
The methyl esters of (L)-phenylalanine and (L)-methionine underwent conjugate additions via their free amino groups to 1-(p-toluenesulfonyl)hexyne, followed by intramolecular acylation of the corresponding enamide anions and tautomerization to afford 2-benzyl-5-n-butyl-3-hydroxy-4-(p-toluenesulfonyl)pyrrole and 5-n-butyl-3-hydroxy-2-(2-methylthioethyl)-4-(p-toluenesulfonyl)pyrrole, respectively. The conjugate additions of a series of acyclic and cyclic secondary β- and γ-chloroamines to acetylenic sulfones proceeded similarly under mild conditions. The resulting adducts were deprotonated with LDA in THF at -78 °C, and the resulting sulfone-stabilized carbanions underwent intramolecular alkylation to afford cyclic enamine sulfones. Thus, acyclic γ-chloroalkylbenzylamines afforded the corresponding 2- or 2,6-disubstituted piperidines, while 2-(chloromethyl)-pyrrolidines, 2-(2-chloroethyl)pyrrolidines, 2-(chloromethyl)piperidines, and 2-(2-chloroethyl)-piperidines produced the corresponding 3-substituted pyrrolizidines, 5- or 3-substituted indolizidines, and 4-substituted quinolizidines, respectively. 8-Methyl-5-substituted indolizidines were also prepared from the appropriate methyl-substituted chloroamine precursor. Enantioselective syntheses were achieved by employing chiral chloroamines derived from amino acids or other enantiopure precursors. Further transformations of several of the products provided concise syntheses of four dendrobatid alkaloids. Thus, reduction of (8aS)-5-n-propyl-6-(p-toluenesulfonyl)-Δ-indolizidine with sodium cyanoborohydride in trifluoroacetic acid, followed by reductive desulfonylation, afforded (-)-indolizidine 167B. The corresponding 5-n-hexyl derivative similarly produced (-)-indolizidine 209D, while (-)-(8R,8aS)-8-methyl-5-n-pentyl-6-(p-toluenesulfonyl)-Δ5,6-indolizidine furnished (-)-indolizidine 209B. Finally, the similar reduction and debenzylation of (-)-(8R,8aS)-5-(2-benzyloxyethyl)-8-methyl-6-(p-toluenesulfonyl)-Δ-indolizid ine produced the corresponding 5-hydroxyethyl indolizidine. This was subjected to chlorination of the alcohol group with thionyl chloride and substitution with a higher order allyl cuprate reagent to afford (-)-indolizidine 207A.
Enantioselective Synthesis of (-)-Pumiliotoxin C from a Chiral Amino Ester and an Acetylenic Sulfone that Acts as an Alkene Dipole Equivalent
Back, Thomas G.,Katsumasa, Nakajima
, p. 6566 - 6571 (2007/10/03)
A new synthesis of the naturally occurring (-)-enantiomer of the dendrobatid alkaloid pumiliotoxin C (1) was achieved by the conjugate addition of methyl (-)-cis-2-amino-trans-6-methylcyclohexanecarboxylate (3) to 1-(p-toluenesulfonyl)-1-pentyne (4), followed by intramolecular acylation to afford (4aS,5R,8aR)-4a,5,6,7,8,8a-hexahydro-5-methyl-2-propyl-3-(p-toluenesulfonyl)-4- quinolinone(2). The acetylenic sulfone thus acts as the synthetic equivalent of an alkene dipole species. The required enantiopure amino ester 3 was obtained by an approach based on pig liver esterase (PLE)-mediated hydrolysis. Thus, the (-)- and (+)-enantiomers of racemic dimethyl trans-3-methylcyclohexane-cis,cis-1,2-dicarboxylate (6) afforded the corresponding half-esters 7 and 8, respectively, when treated with PLE. The desired half-ester 7 was recovered intact after selective conversion of the free carboxylic acid group of the byproduct 8 into its benzyl ester. Half-ester 7 was converted into enantiopure (-)-6 with diazomethane, followed by regioselective saponification and Curtius rearrangement to afford the required enantiopure key intermediate 3. Finally, hydrogenation of the enol triflate of enaminone 2, followed by reductive desulfonylation, afforded the product (-)-1.
Use of an acetylenic sulfone as an alkene dipole equivalent in the synthesis of (±)-pumiliotoxin C
Back, Thomas G.,Nakajima, Katsumasa
, p. 989 - 992 (2007/10/03)
The cycloaddition of methyl cis-2-amino-trans-6-methylcyclohexanecarboxylate (3) with 1-p-(toluenesulfonyl)-1-pentyne (4) afforded the corresponding enaminone 2, that was in turn reduced to (±)-pumiliotoxin C (1). The acetylenic sulfone 4 thus functions as the synthetic equivalent of the alkene dipole 5 in this process.
Reactions of (E)-2-Iodo-1-tosyl-1-alkenes as Useful Synthetic Intermediates
Iwata, Noriyoshi,Morioka, Tetsuro,Kobayashi, Toshifumi,Asada, Takahiro,Kinoshita, Hideki,Inomata, Katsuhiko
, p. 1379 - 1388 (2007/10/02)
(E)-2-Iodo-1-tosyl-1-alkenes readily available by iodosulfonization of 1-alkynes were found to be useful synthons for the regio- and/or stereoselective preparation of 1-tosyl-1-alkynes, 1-tosyl-2-alkynes, (Z)-vinyl and (Z)-allyl sulfones, β-tosyl enamines
