Transannular bromination

Addition of bromine to cyclonona-1,2-diene takes place with formation of transannular bromination products predominating, but no such products are obtained from cyclo-octa-1,2-diene or cyclodeca-1,2-diene. ... 

No product derived from the transannular hydrogen abstraction is observed in the addition of bromotrichloromethane because bromine-atom abstraction is sufficiently rapid to prevent effective competition by the intramolecular hydrogen abstraction. 

Dimethyl tricyclo[4.2.2.02 -5]deca-3,7-diene-9,10-dicarboxylate adds bromine and iodine only to the less hindered double bond to give the syn 1,2-addition product of the cyclobutene moiety79. The product composition from this compound depends on the temperature and the solvent. At high temperatures, the 1,2-addition predominates over the transannular reaction, but this predominance is small in a solvent like chloroform and is lost in a protic solvent such as acetic acid (equation 47). 

A transannular reaction involving a through-space interaction has been observed also when bromine was added to homohypostrophene (40). The bromination proceeds straightforwardly by 1,4-addition to give exclusively the dibromo adduct 41 (equation 49)80. 

In an interesting fragmentation reaction, the hexahydroazocine (23) is formed by solvolysis of (22) in the presence of NaBHt in 94% yield (75TL2613). A related compound (24) can be prepared from 4-cycloheptenone oxime tosylate via the unsaturated lactam (25) (79JOC287). Whereas (25) adds bromine to the double bond, (24) undergoes a transannular reaction to give a 1-substituted pyrrolizidine (26). The latter type of reaction also occurs... 

A single diastereomer 3 was obtained after crystallization from the reaction mixture on cis addition to (—)-caryophyllene98 10°. The diastereomer 3 undergoes transannular radical addition on treatment with bromine or iodine to give a stable nitroxide radical 4 (X-ray)98,99. 

On treatment with electrophilic reagents such as bromine and hydrogen bromide, 38 gave diphenylbenzofulvenes (45) through transannular bond formation between proximate triple bonds (44) , whereas addition of bromine to 41 yielded the... 

When 1-aza-4-cyclooctene was treated with various electrophiles, pyr-rolizidines 81 were formed.117 A reaction mechanism proceeding via transannular attack by nitrogen was postulated. The l-aza-4-cyclooctene-8-one did not undergo ring contraction on bromination and yielded the ordinary dibromolactam. 

The reaction of cyclohepta-1,4-diene and cycloocta-1,4-diene with electrophiles (bromine, iodine) results in transannular 7t-cyclization. Thus, reaction of cyclohepta-1,4-diene with silver(I) perchlorate and iodine in methanol gave /ranj-2,5-dimethoxybicyclo[4.1.0]heptane (26, n = 1) in 56% yield. Cycloocta-1,4-diene reacted similarly. ... 

A transannular route to 1-substituted pyrrolizidines has recently been reported by Wilson and Sawicki. The lactam (79) was prepared by Beckmann rearrangement of the oxime p-toluenesulfonate of cyclohept-4-enone. Reduction with lithium aluminum hydride gave the amine (80), which on treatment with bromine yielded the 1-bromopyrrolizidine (81) in one stereospecific step (95%). The stereochemistry of the product corresponds to a disfavored exo-mode of cyclization by attack of the nitrogen on the bromonium ion. Further modification of this route to produce naturally occurring alkaloids would appear feasible, but has not yet been reported. 

Only acyclic addition compounds are obtained from monosubstituted 1,6-hepta-dienes. Use of bromine leads only to addition products. lodocylization is also observed when transannular interactions are possible 1,5-cyclodecadiene -> 1,4-diodo-cij-decalin. ... 

Aryl derivatives of 23 are readily degraded with chlorine to dithiatriazines 94 with the rate being dependent on the aryl substituent. The phenyl derivative of 23 undergoes nucleophilic attack by triphenylphosphine or triphenylarsine and is transformed into the monocyclic eight-membered imino compound 95, which has weak transannular S-S bonds (Scheme 2). Thermolysis and photolysis of compounds 23 affords the corresponding 1,2,3,5-dithiadiazolyl radicals. The trifluoromethyl derivative of 23 (R = Cp3) is astonishingly stable and does not react with bromine, chlorine, sulfuryl chloride, or (Cp3)2NO. To date, no explanation has been found <2003EJI3211>. 

This synthetic strategy has been extended by the same authors to the synthesis of the ring system of the loline alkaloids. Seven simple loline alkaloids [e.g. loline (9)] and one dimeric species have been identified (see these Reports, Vol. 8, Ch. 3). The ketone (10) was converted into the amine (11) in analogous fashion to the formation of (7) from cyclohept-4-enone (see Scheme 3). Treatment of the amine (11) with bromine led to transannular cyclization and formation of the 3-aza-9-oxabrendane system (13) in good yield (85%), as shown in Scheme 4. The... 

No product derived from the transannular hydrogen abstraction is observed in the addition of bromotrichloromethane, because bromine atom abstraction is sufficiently rapid to prevent effective competition by the hydrogen-abstraction process. Another example of transannular cyclization of unsaturated radicals is found in the reaction of 1,4-cyclooctadiene with acetaldehyde in the presence of benzoyl peroxide, which gives a cyclized ketone by a process involving an intramolecular addi-... 

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