由亚双环丙基及其一些衍生物立体选择性制备六种非对映异构四环丙烷。
Stereoselective preparation of six diastereomeric quatercyclopropanes from bicyclopropylidene and some derivatives.
作者信息
von Seebach Malte, Kozhushkov Sergei I, Schill Heiko, Frank Daniel, Boese Roland, Benet-Buchholz Jordi, Yufit Dmitry S, de Meijere Armin
机构信息
Institut für Organische und Biomolekulare Chemie der Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany.
出版信息
Chemistry. 2007;13(1):167-77. doi: 10.1002/chem.200600799.
Diastereomeric meso- and d,l-bis(bicyclopropylidenyl) (5) were obtained upon oxidation with oxygen of a higher-order cuprate generated from lithiobicyclopropylidene (4) in 50 and 31 % yield, respectively. Their perdeuterated analogues meso-[D(14)]- and d,l-[D(14)]-5 were obtained along the same route from perdeuterated bicyclopropylidene [D(8)]-3 (synthesized in six steps in 7.4 % overall yield from [D(8)]-THF) in 20.5 % yield each. Dehalogenative coupling of 1,1-dibromo-2-cyclopropylcyclopropane (6) gave a mixture of all possible stereoisomers of 1,5-dicyclopropylbicyclopropylidene 16 in 69 % yield, from which (Z)-cis-16 was separated by preparative gas chromatography (26 % yield). The crystal structure of meso-5 looks like a superposition of the crystal structures of two outer bicyclopropylidene units (3) and one inner s-trans-bicyclopropyl unit, whereas the two outer cyclopropyl moieties adopt a gauche orientation with respect to the cyclopropane rings at the inner bicyclopropylidene units in (Z)-cis-16. Birch reduction with lithium in liquid ammonia of meso-5 and d,l-5 gave two pairs of diastereomeric quatercyclopropanes trans,trans-(R*,S*,R*, S*)-17/cis,trans-(R*,S*,R*,R*)-18 and trans,trans-(R*,S*,S*,R*)-19/cis,trans-(R*,S*,S*,S*)-20 in 97 and 76 % yield, respectively, in a ratio 9:1 for every pair. The latter diastereomer was also obtained as the sole product by Birch reduction of (Z)-cis-16 in 96 % yield. Under the same conditions, tetradecadeuterio analogues trans,trans-[D(14)]-(R*,S*,R*,S*)-17/cis,trans-[D(14)]-(R*, S*,R*,R*)-18 (8:1) and trans,trans-[D(14)]-(R*,S*,S*,R*)-19/cis,trans-[D(14)]-(R*,S*,S*,S*)-20 (12:1) were prepared from meso-[D(14)]-5 and d,l-[D(14)]-5 in 37 and 63 % yield, respectively. Reduction of meso-5 with diimine gave the cis,cis-quatercyclopropane (S*,S*,R*,R*)-21 as the main product (58 % yield) along with the cis,trans-diastereomer (S*,S*,R*,S*)-18 (29 % yield). Thus, five of the six possible diastereomeric quatercyclopropanes were obtained from meso-5, d,l-5, and (Z)-cis-16. The X-ray crystal structure analyses of trans,trans-(R*,S*,R*,S*)-17 and cis,cis-(S*,S*,R*,R*)-21 revealed for the both an unusual conformation in which the central bicyclopropyl unit adopts an s-trans-(antiperiplanar) orientation with phi=180.0 degrees , and the two terminal bicyclopropyl moieties adopt a synclinal conformation with phi=49.8 and 72.0 degrees , respectively. In solution the vicinal coupling constants (3)J(H,H) in trans,trans-(R*,S*,R*,S*)-[D(14)]-17, trans,trans-(R*,S*,S*,R*)-[D(14)]-19, trans,cis-(R*,S*,R*,R*)-[D(14)]-18 and trans,cis-(R*,S*,S*,S*)-[D(14)]-20 were found to be 4.1, 4.7, 5.9 and 5.9 Hz, respectively. This indicates a predominance of the all-gauche conformer in (R*,S*,R*,S*)-17 and a decreasing fraction of it in this sequence of the other diastereomers.
用氧气氧化由双环丙基锂（4）生成的高阶铜酸盐，分别以50%和31%的产率得到非对映异构体的内消旋和外消旋 - 双（双环丙基亚基）（5）。它们的全氘代类似物内消旋 - [D(14)] - 和外消旋 - [D(14)] - 5是通过相同的路线，由全氘代双环丙基[D(8)] - 3（以[D(8)] - 四氢呋喃为原料经六步合成，总产率为7.4%）分别以20.5%的产率得到的。1,1 - 二溴 - 2 - 环丙基环丙烷（6）的脱卤偶联反应以69%的产率得到1,5 - 二环丙基双环丙基亚基16的所有可能立体异构体的混合物，其中（Z） - 顺式 - 16通过制备气相色谱分离得到（产率26%）。内消旋 - 5的晶体结构看起来像是两个外部双环丙基亚基单元（3）和一个内部s - 反式双环丙基单元的晶体结构的叠加，而在（Z） - 顺式 - 16中，两个外部环丙基部分相对于内部双环丙基亚基单元处的环丙烷环呈gauche取向。在内消旋 - 5和外消旋 - 5的液氨中用锂进行Birch还原反应，分别以97%和76%的产率得到两对非对映异构体四环丙烷反式，反式 - （R*，S*，R*，S*） - 17 / 顺式，反式 - （R*，S*，R*，R*） - 18和反式，反式 - （R*，S*，S*，R*） - 19 / 顺式，反式 - （R*，S*，S*，S*） - 20，每对的比例为9∶1。后一种非对映异构体也是通过（Z） - 顺式 - 16的Birch还原反应以96%的产率作为唯一产物得到的。在相同条件下，由内消旋 - [D(14)] - 5和外消旋 - [D(14)] - 5分别以37%和63%的产率制备了全十四氘代类似物反式，反式 - [D(14)] - （R*，S*，R*，S*） - 17 / 顺式，反式 - [D(14)] - （R*，S*，R*，R*） - 18（8∶1）和反式，反式 - [D(14)] - （R*，S*，S*，R*） - 19 / 顺式，反式 - [D(14)] - （R*，S*，S*，S*） - 20（12∶1）。用二亚胺还原内消旋 - (5)得到顺式，顺式 - 四环丙烷（S*，S*，R*，R*） - (21)作为主要产物（产率58%），同时还有顺式，反式非对映异构体（S*，S*，R*，S*） - 18（产率29%）。因此，从内消旋 - 5、外消旋 - 5和（Z） - 顺式 - 16得到了六种可能的非对映异构体四环丙烷中的五种。反式，反式 - （R*，S*，R*，S*） - 17和顺式，顺式 - （S*，S*，R*，R*） - 21的X射线晶体结构分析表明，两者都具有不寻常的构象，其中中心双环丙基单元呈s - 反式（反式共平面）取向，φ = 180.0°，两个末端双环丙基部分分别呈顺错构象，φ = 49.8°和72.0°。在溶液中，反式，反式 - （R*，S*，R*，S*） - [D(14)] - 17、反式，反式 - （R*，S*，S*，R*） - [D(14)] - 19、反式，顺式 - （R*，S*，R*，R*） - [D(14)] - 18和反式，顺式 - （R*，S*，S*，S*） - [D(14)] - 20中的邻位耦合常数（3）J(H,H)分别为4.1、4.7、5.9和5.9 Hz。这表明在（R*，S*，R*，S*） - 17中全gauche构象占主导，而在该序列的其他非对映异构体中其比例逐渐降低。
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