2- Substituted bicyclo heptane

For enr/o-substituted bicyclo[2.2.1]heptan-7-ones, the following product ratios are observed. Offer an explanation for the substituent effect. 

The predictable stereochemistry of the ring closure of substituted 5-hexenyllithiums, coupled with the ease with which the product organolithium may be functionalized, permits rational design of synthetic routes to polycyclic systems by sequential anionic cyclizations of polyolefinic alkyllithiums.12 The preparation of stereoisomerically pure e do-2-substituted bicyclo[2.2.1]heptanes is illustrative of this approach to polycyclic systems.12... 

However, cyclopropanation of cyclohexene with methyl (a-diazomethyl)acrylate 3 in the presence of copper(II) trifluoroacetate furnished the 7-exo-substituted bicyclo-[4.1.0]heptane preferentially28). 

Quin, L.D. and Littlefield, L.B., Importance of the structure of the phosphorus functionality in allowing dihedral angle control of vicinal 13C-31P coupling. Carbon-13 NMR spectra of 7-substituted bicyclo[2,2,l]heptane derivatives,. Org. Chem., 43, 3508, 1978. 

Unfortunately, the situation is even more complicated In bi- and tricyclic compounds the a-SCS may experience further alterations apparently produced by intramolecular strain. The usually large a-SCS(CH3) in 1-methyl-bicyclo[2.2.1]heptane (9) (93) has already been mentioned. The a-effects of other substituents (OH, OCH3, Cl, I, and COOH) in the same molecular system do not correlate with those in bridgehead-substituted bicyclo[2.2.2]octanes or adamantanes again this was attributed to internal strain (125). The a-SCS(F)... 

X, using dissociative electron-transfer theory. A through-space stabilizing interaction (homohyperconjugation) in the 4-X-substituted bicyclo[2.2.1]heptane radical species has been shown to exist. 

The copper-catalyzed photobicyclization of acyclic 1,6-dienes to bicyclo[3.2,0]heptanes using the bis[copper(l) lrifluoromethanesulfonate]benzene complex has found general and synthetic utility in the conversion of diallyl and homoallyl vinyl ethers to 3- or 2-oxabicyclo[3.2.0]heptanes,5 6 of /V-allyl-A -2-methyl-2-propenecarbamates to iV-carboethoxy-3-azabicyclo[3.2.0]heptanes 7 and of allylic alcohols to the corresponding hydroxy-substituted bicyclo[3.2.0]heptanes.8 9 Examples of such reactions are summarized below. 

There are many examples of 1234-1243 rearrangements. In particular, the reaction provides a useful route to bridgehead-substituted bicyclo[3.2.0]heptanes, but is normally in competition with the homoallyl rearrangement (see Section 2.1.). There are three main possibilities for the preparation of cyclobutanes ... 

A similar rearrangement converted a 3-bromopropyl-substituted bicyclo[3.2.0]heptan-6-one 5 to fra i-octahydronaphthalen-l(2//)-one 6.118... 

Longifolene (the world s most abundant sesquiterpene) is a substituted bicyclo[2.2.1]heptane system with an exocyclic double bond and a bridging hydrocarbon chain which very effectively shields the exo face of the double... 

Tomas and his colleagues employed Diels-Alder methodology to prepare a series of racemic 3-substituted bicyclo[2.2.1]heptan-2-ylstannanes and related compounds (28-31) (Scheme 6)44. The use of optically-pure (R)-4,4-dimethyl-2-oxotetrahydrofuran-3-yl ( )-3-triphenylstannylprop-2-enoate afforded the optically-pure adduct (32) after separation... 

Treatment of 3-en /o-methoxytricyclo[3.2.0.0 ]heptan-6-one (1) with aqueous solutions of bromide and chloride afforded the respective 7-anf/-substituted bicyclo[2.2.1]heptanones... 

The versatility of the addition reaction of organocuprates to activated cyclopropanes and the stereospecificity have made this reaction an important step in the synthesis of a variety of natural products such as prostaglandins and sesquiterpenes.One of the advantages of this reaction lies in the possibility of introducing complete side chains into certain structures. An example is the reaction of 3-e Jo-substituted tricyclo[3.2.0.0 ]heptan-6-ones 17 with the lithium cuprate that contains a side chain with a protected functional group. The substituted bicyclo[2.2.1]heptan-2-ones 18 were obtained in high yields. 

However, the stereoselectivity changed completely when phenyP or ethoxycarbonyl substitu-ents were incorporated at C2. The initial 2-oxocyclohexylmethyl radical 21 cyclized to give a 6-substituted bicyclo[4.1.0]heptan-l-oxyl radical, which preferentially rearranged by fi-scission of the inter-ring bond, presumably because the product radical is resonance stabilized. This resulted in ring expansion and 3-substituted cycloheptanones 22 were isolated in good yields. 

Hydrogen abstraction from bicyclo[4.1.0]heptan-2-ols 30 by tert-butoxyl radicals took place at the a-position, adjacent to the hydroxyl group and cyclopropane ring, to generate substituted bicyclo[4.1.0]hept-2-yl radicals which rearranged to give 3-methylcyclohexanones 31 as the main products. ... 

Ring expansion of the substituted bicyclo[4.1.0]heptanes 8, formed by addition of chloromethyl-carbene to silyl enol ethers, was accomplished almost equally effectively by refluxing in toluene, or by heating in methanol containing triethylamine. In each case, the crude mixture of cis- and /rani-7-chloro-7-methylbicyclo[4.1. Ojheptanes 8 was used, although it was observed that the traui-isomers, with the chlorine and trimethylsiloxy substituents tram to each other, rearranged more rapidly. 

When there is a suitably placed benzylic C-H bond, the cyclization occurs in good yield, leading either to benzobicyclo[3.1.0]hexanes 3,5 6 benzobicyclo[4.1,0]heptanes 4,6 or phenyl-substituted bicyclo[3.1.0]hexanes 5 and 6.4... 

The tricyclic ketone (387) which has been suggested as an intermediate in the transformation of the exo-2-bromobicyclo[3,2,0]heptane-6-ones to anti-7-substituted bicyclo[2,2,l]heptan-2-ones has been isolated. Treatment of (388) with sodium hexamethyldisilazide gave (387), whose structure was confirmed by single-crystal J -ray crystallography. Reaction of (387) with potassium cyanide in methanol containing a catalytic amount of methoxide gave anti-7-cyano-5-bromobicyclo[2,2,l]-heptanone (389). The availability of (387) should allow an increase in the range of... 

Some examples of diastereoisomers are given in Figure 8.3 (tartaric acid and some monosaccharides) [1-3,10], Figure 8.4 (1,2-dimethylcyclohexane, decaline, 2-substituted bicyclo[2.2.1]heptane) [4], and Figure 8.5 (1,2-diphenylmethylglycol) [1,4]. 

FIGURE 8.4 Examples of some diastereoisomers of different cyclic compounds. 1,2-Dimethylcyclohexane (a, b — enantiomers a, c and b, c — diastereoisomers) (e,e)-(a, a) — (e, a) (e—equatorial a—axial) — conformational diastereoisomers trans-cis — configurational diastereoisomers Decaline trans-cis — configurational diastereoisomers 2-Substituted bicyclo[2.2.1]heptane exo-endo — configurational diastereoisomers. 

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