von Seebach Malte, Kozhushkov Sergei I, Schill Heiko, Frank Daniel, Boese Roland, Benet-Buchholz Jordi, Yufit Dmitry S, de Meijere Armin
Institut für Organische und Biomolekulare Chemie der Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany.
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。
