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
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
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DOI：
10.1021/jo000080p
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发表时间：
2000-07-28
影响因子：
3.6
通讯作者：
Nakajima, K
中科院分区：
文献类型：
--
作者：
Back, TG;Nakajima, K
（L）-苯丙氨酸甲酯和（L）-蛋氨酸甲酯分别通过其游离氨基与1-（对甲苯磺酰基）己炔发生共轭加成反应，然后与相应的烯酰胺阴离子发生分子内酰化反应和互变异构反应，分别得到2-苄基-5-正丁基-3-羟基-4-（对甲苯磺酰基）吡咯和5-正丁基-3-羟基-2-（2-甲硫基乙基）-4-（对甲苯磺酰基）吡咯。在温和的条件下，一系列无环和环状仲β-和γ-氯胺与炔砜的共轭加成反应进行类似。将所得加合物在-78 ° C下在THF中用LiA去质子化，并且使所得砜稳定的碳负离子经历分子内烷基化以得到环状烯胺砜。因此，无环γ-氯烷基苄胺得到相应的2-或2，6-二取代的哌啶，而2-（氯甲基）吡咯烷、2-（2-氯乙基）-吡咯烷、2-（氯甲基）-哌啶和2-（2-氯乙基）-哌啶分别产生相应的3-取代的吡咯烷、5-或3-取代的吲嗪和4-取代的喹嗪。还从适当的甲基取代的氯胺前体制备了8-甲基-5-取代的吲嗪。利用氨基酸衍生的手性氯胺或其他对映体前体实现了对映体选择性合成。几个产物的进一步转化提供了四个石斛生物碱的简明合成。因此，在三氟乙酸中用氰基硼氢化钠还原（8aS）-S-正丙基-6-（对甲苯磺酰基）-δ（5，6）-中氮茚，然后进行还原性内酰化，得到（-）-中氮茚167 B。相应的5-正己基衍生物类似地产生（-）-中氮茚209 D，而（-）-（8 R，8aS）-8-甲基-5-正戊基-6-（对甲苯磺酰基）-δ（5，6）-中氮茚提供（-）-中氮茚209 B。最后，（-）-（SR，8aS）-5-（2-苄氧基乙基）-8-甲基-6-（对甲苯磺酰基）-δ（5，6）-吲嗪经类似的还原和脱苄基反应生成相应的5-羟乙基吲嗪。用亚硫酰氯对醇基进行氯化，并用更高级的烯丙基铜酸酯试剂取代，得到（-）-吲嗪207 A。
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-toluene sulfonyl)pyrrole, respectively. The conjugate additions of a series of acyclic and cyclic secondary beta- and gamma-chloroamines to acetylenic sulfones proceeded similarly under mild conditions. The resulting adducts were deprotonated with LI)A in THF at -78 degrees C, and the resulting sulfone-stabilized carbanions underwent intramolecular alkylation to afford cyclic enamine sulfones. Thus, acyclic gamma-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)-S-n-propyl-6-(p-toluenesulfonyl)-Delta(5,6)-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)-Delta(5,6)-indolizidine furnished (-)-indolizidine 209B. Finally, the similar reduction and debenzylation of (-)-(SR, 8aS)-5-(2-benzyloxyethyl)-8-methyl-6-(p-toluenesulfonyl)-Delta(5,6)-indolizidine 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.