6-烯-8-羰基-1-叔丁氧基羰基氮杂螺[4,4]壬烷的合成

以烯丙基脯氨酸甲酯(1)为起始原料, 经7步反应以42%的总收率得到了三尖杉碱合成中的重要中间体6-烯-8-羰基-1-叔丁氧基羰基氮杂螺[4,4]壬烷(7). 关键反应为构筑螺环季碳的[2,3]斯蒂文森重排(Stevens rearrangement)及烯丙基双键加氧的酸内酯化反应(Acid-lactonization reaction).     

螺[4,4]-1,6-壬二烯骨架手性双膦配体的合成

从方便易得的原料出发,以钯催化的烯基三氟甲磺酸酯与二苯基膦氧化物的偶联反应为关键步骤,合成了螺[4,4]-1,6-壬二烯骨架的手性双膦配体1.其中,关键中间体5的拆分是通过半制备手性液相色谱实现的,并通过该化合物的X射线单晶衍射分析确定了其中螺碳原子的绝对构型.配体(S)-1的Rh(I)络合物在α-乙酰氨基肉桂酸的氢化中表现出中等的对映选择性(53%ee).配体(S)-1的Cu(I)络合物能以较好的反应活性实现苯乙酮的不对称氢化,产物的对映体过量可以达到67%.     

光活性[1]1-联萘酚(BINOL)的不对称合成

由于 1 ,1 -联萘酚 ( BINOL)可作为手性配体或手性催化剂的前体 ,在不对称合成反应中具有广泛的应用 [1,2 ] ,所以如何得到光学纯的 BINOL的研究吸引了许多化学家的注意 .制备光学活性的 BINOL的方法较多 ,但一般效果较好的是用拆分的方法[3,4] .通过 2 -萘酚不对称氧化偶联直接得到 BINOL的方法也有许多报道 [5 ,6 ] ,但结果都不理想 .近来 ,Kocovsky等 [7]用鹰爪金碱作为手性诱导试剂 ,在Cu Cl2 存在下 ,2 -萘酚偶联得 BINOL,其 ee值为 1 0 0 % ,但产率只有 1 4% ,且由于鹰爪金碱价格昂贵 ,限制了该法的应用 .在此基础上 ,我…     

经由氮杂邻联烯醌中间体合成轴手性化合物的研究进展

轴手性化合物不仅是不对称合成领域重要的催化剂和配体,许多天然产物和药物也是轴手性化合物.因此,发展轴手性化合物的高效合成方法是有机化学的重要研究课题.相对已经被广泛研究的邻联烯醌中间体,基于氮杂邻联烯醌中间体的不对称催化反应近年来才受到人们的关注,研究相对较少,有着很大的发展空间.总结了经由氮杂邻联烯醌中间体构建轴手性化合物的研究进展,介绍了反应范围、机理和合成应用.最后对该研究领域的发展前景进行了总结和展望.     

合成2-丁基-1,3-二氮杂螺[4.4]壬-1-烯-4-酮的工艺改进

以1-氨基环戊腈草酸盐为起始原料,经双氧水水解、戊酰氯酰化、环合制得厄贝沙坦的关键中间体——2-丁基-1,3-二氮杂螺[4.4]壬-1-烯-4-酮,总产率80.9%,其结构经1H NMR,13C NMR和MS确证。     

手性螺环配体的合成及其在不对称催化反应中的应用研究进展

手性螺环配体的合成及其在不对称催化反应中的应用是不对称合成和催化研究中重要的研究领域之一, 一些手性螺环配体被合成出来并成功地应用于不对称催化反应中. 综述了近十年来手性螺环配体的合成及在不对称催化反应中的应用研究进展.     

2-氮杂双环[3.1.0]己烷-3-羧酸的不对称合成

设计了以D-谷氨酸或L-谷氨酸为原料,经氨基保护、4-二甲氨基吡啶(DMAP)催化环合、还原脱水成烯、不对称Simmons-Smith反应、水解,高立体选择性合成2-氮杂双环[3.1.0]己烷-3-羧酸的路线.用1H NMR,13C NMR,单晶X衍射等对中间体及目标产物进行了结构表征.优化了DMAP催化环合、Simmons-Smith和水解反应的工艺条件,结果表明,DMAP催化环合反应在原料比为n(DMAP)∶n(二碳酸二叔丁酯)∶n(吡啶)=0.40∶4.0∶1.0条件下,(R)-5-氧代吡咯-1,2-二甲酸二叔丁酯的收率可达82%;Simmons-Smith反应随着反应时间延长,顺式结构与反式结构含量比不断变化,直到反应时间为19.5 h时,顺式与反式达到最佳比为6∶1,收率为75%.总收率达30%,de值72%.     

手性5-(R)-(1′R,2′S,5′R)-孟氧基丁内酯并[3,4-b]-2(S)-6(R)-1-N-环己基氮杂环丙烷的合成及晶体结构

环己胺与手性元5-(R)-(1′R,2′S,5′R)-孟氧基-3-溴-2(5H)-呋喃酮的不对称M ichael加成/分子内亲核取代反应,得到含有两个新手性中心的氮杂环丙烷/稠合丁内酯标题化合物。对其进行了谱学表征和X-射线单晶衍射测定。标题化合物分子式为C20H33NO3,M r=335.47,三斜晶系,P1空间群,晶胞参数:a=5.438(11)。A,b=8.117(2)。A,c=11.572(2)。A,α=96.84(3)°,β=94.48(3)°,γ=101.86(3),°V=493.5(2)。A3,Z=1,D c=1.129g/cm3,R=0.0867,wR=0.2344。     

2-[二-(2-氯乙基)-胺基]-5-苄氧基-1,3,2-氧氮磷杂环己烷-2-氧化物的不对称合成

2-[二-(2-氯乙基)-胺基]-5-苄氧基-1,3,2-氧氮磷杂环己烷-2-氧化物是抗癌药物Endoxan的衍生物,其光学异构体的合成已有报道.本文报道了我们从廉价易得的手性原料天然-L-酒石酸开始,通过较为简捷的合成路线,完成了对目标化合物全部4个光学异构体的合成.化合物的有关数据参见表1.     

不对称催化合成中手性膦配体的研究进展(Ⅰ)(待续)

对近十多年来不对称催化合成领域中出现的手性膦配体进行了综述,按其不对称中心以及结构上的特征加以分类,并对其催化性能进行总结。     

Synthesis and properties of 1,6-dioxaspiro[4.4]nonane and its derivatives (review)

Data on methods of synthesis and the chemical properties of 1,6-dioxaspiro-[4.4]nonane and its derivatives are correlated.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1155–1168, September, 1986.     

One-Step Synthesis of the 1-Azaspiro[5.5]undecane Skeleton Characteristic of Histrionicotoxin Alkaloids from Linear Substrates via Hg(OTf)2-Catalyzed Cycloisomerization

Histrionicotoxin (HTX) alkaloids isolated from the poison arrow frogs possess a unique structure characterized by a 1-azaspiro[5.5]undecane skeleton common to the HTX family. The unique molecular architecture of HTXs and the interest as potential target drugs have prompted synthetic chemists to promote the total synthesis so far. However, all of the synthetic strategies to access the 1-azaspiro[5.5]undecane framework of HTXs take a multistep approach from linear starting materials due to stepwise construction of either six-membered carbo- or azacycle. Herein, we report the direct one-step construction of the 1-azaspiro[5.5]undecane skeleton from linear amino ynone substrates bearing an N-methoxycarbonyl group utilizing our mercuric triflate (Hg(OTf)₂)-catalyzed cycloisomerization reaction. The utility of this novel methodology was demonstrated by the total and formal syntheses of HTX-235A and HTX-283A, respectively, from the azaspirocycle.     

Synthesis and Structure of 8-Methyl-2-methylene-1,4,6,9-tetraoxaspiro[4.4]nonane

By reacting propylene carbonate with epichlorohydrin 8-methyl-2-chloromethyl-1,4,6,9-tetra- oxaspiro[4.4]nonane was obtained that afforded 8-methyl-2-methylene-1,4,6,9-tetraoxaspiro[4.4]nonane on dehydrochlorination. The spirocompounds synthesized are composed of stereoisomers mixtures containing: cis,syn-, cis,anti-, trans,syn-, trans,anti-isomers and cis,syn-, cis,anti-isomers, respectively. These isomers are distinguished by a different orientation of substituents in positions 2 and 8 with respect to two five-membered rings.     

Practical synthesis of enantiopure spiro[4.4]nonane C-(2'-deoxy)ribonucleosides

The levorotatory diol 7 has been sequentially monosilylated, dehydrated, and oxidized at the allylic methylene group to provide (+)-12. The enantiomeric dextrorotatory diol 7 has been directed down a different sequence of steps involving monosilylation, dehydration, hydroboration, Swern oxidation, and regioselective introduction of a conjugated double bond to generate (-)-33. The novel feature of these transformations is that two key deoxycarbospironucleoside intermediates of the proper absolute configuration have been made available from enantiomerically related precursors. Also reported is a highly practical and reliable means for the formation of novel 2'-deoxyribonucleosides of novel structural type from these spirocyclic cyclopentenones.     

Synthesis of 2-azaspiro[4.4]nonan-1-ones via phosphine-catalysed [3+2]-cycloadditions

The phosphine-catalyzed [3+2]-cycloaddition of the 2-methylene γ-lactams 4 and 5 and the acrylate 6 with the ylides derived from the ethyl ester, the amide or the chiral camphor sultam derivative of 2-butynoic acid (7a-c) give directly, or indirectly after reductive cyclization, spiro-heterocyclic products. The acid 32 underwent Curtius rearrangement and then acid hydrolysis to give two novel spiro-cyclic ketones, 41 and 42.     

1-[4-(二甲氨基)苯亚甲基氨基]-4-苯基硫脲的合成及手性晶体结构

对二甲氨基苯甲醛和苯基氨基硫脲缩合反应生成对二甲氨基苯甲醛缩氨基苯硫脲{1-[4-(dimethylamino)ben- zylidene]-4-phenylthiosemicarbazide}, 并从溶液中析出手性晶体. 元素分析、红外光谱、紫外光谱、核磁谱、质谱和X射线衍射测定其组成和结构. 晶体属正交晶系, P2₁2₁2₁空间群, a＝0.77038(14) nm, b＝1.1428(2) nm, c＝1.6726(3) nm, V＝1.4726(5) nm³, Z＝4, D_c＝1.346 g/cm³, F(000)＝632, μ＝0.219 mm^－1, 可观测点精修最终偏离因子: R＝0.0407, wR＝0.1157. 化合物的晶体结构和固态圆二色谱表明化合物在结晶过程中发生单一对映体的手性堆积.     

Enantioselective Synthesis of 3- Azabicyclo[4.3.0]nonane Alkaloids

The stereospecific synthesis of the monoterpene alkaloids (?)-α-skytanthine ((?)- 2 ), (?)-N -demethyle-δ-sky-tanthine((?)- 7 ), and (+)-epidihydrotecomanine (+)- 4 was achieved from a common intermediate 22 , which in turn was obtained from (1R,4S,1′S)-2-(1′-phenylethyl)-2-azabicyclo[2.2.1]hept-5-ene (10) ,via a ketene aza-Claisen rearrangement. The piperidine derivative (+)- 31 , formally the aza-analogue of (+)-isoiridomyrmecin, was also obtained from the same intermediate 22 .