Stereoselective preparation of six diastereomeric quatercyclopropanes from bicyclopropylidene and some derivatives

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 )-171cis,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,cisquatercyclopropane (S ,S ,R ,R )-21 as the main product (58% yield) along (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 )-191cis,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. ne 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 strans- (anti periplanar) 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, trns,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.