Transannular addition

Die radikalische Aminierung von 1,5-Cyclooctadien mittels Hydroxylamin/Titan(III)-chlorid in konzentrierter Salzsaure verlauft unter gleichzeitiger transannularer Addition und ergibt exo-2-Amino-cis-bicyclo[3.3.0]octan2. Die Stoffbilanz dieser Reaktion entspricht einer einfachen Addition von Ammoniak an das Dien. 

The lack of formation of transannular addition products was taken as evidence of the single-step formation of a transition state with little or no ionic character. 

In the carbonylation of unconjugated dienes the nature of the products is influenced by reaction conditions. With Pd halides in ethanol at 100°C and 97 atm CO, 1,5-cyclooctadiene is successively carbonylated to the unsaturated monoester and then to the saturated diester (II). With (Ph3P)2PdCl2 in ethanol-HCl and 300-700 atm CO, the monoester is produced selectively at 60°C and the diester at 100°C (8). Finally, with (Bu3P)2PdI2 in THF at 150°C and 1000 atm CO, 1,5-cyclooctadiene undergoes transannular addition of CO to give a cyclic ketone in 40-45% yield (14, 15). The mechanism proposed involves a a-7r-cyclooctenyl... 

It was thus of interest to determine whether a transannular addition could occur for the cyclo-octenyl radical. The cyclo-octenyl radical has been prepared from its parent halohydrocarbon in several matrices in the rotating cryostat. At 77°K the radical was stabilized in all of the matrices but when the samples were warmed reaction took place. The e.s.r. spectra showed that the main reaction in matrices of water, benzene or camphane was hydrogen abstraction adjacent to the double bond to give a cyclic allyl radical (9) rather than the bicyclic radical. However, in a matrix of bicyclopentadiene dimer cyclization occurs to give the bicyclic radical and in a matrix of adamantane both allylic and bicyclic radicals were formed. 

Unlike the case of the hexenyl radical, the mode of reaction of the cyclo-octenyl radical is affected by the matrix. However, the results show that transannular addition can occur in a suitable matrix at 77°K, and thus can probably occur readily in the liquid phase where there is less steric control on the conformation of the cyclo-octenyl radical. 

The SET (single electron transfer) mechanism can be invoked in the transannular addition of secondary amines to 1,1-diarylalkcncs in the presence of a catalytic amount of butyllithium, sodium naphthalenide or potassium hydroxide52, since the regiochemistry which is observed is opposite to that predicted by assuming the formation of metal amides. 

This approach has also been exploited for the transannular addition of nitriles to 5//-dibenzo-[o// cycloheptenes 31. In fact, by treatment with sulfuric acid in acetonitrile, bridged products 32 were obtained as sole isomers, the stereochemistry was assigned by Ml NMR and confirmed by X-ray analysis188. 

This transannular addition of a-sulfinyl carbanions to nonactivated double bonds is utilized as the key step in a synthesis of trans-1-thiadecalin (70) in enantiomerically pure form. The required ( )-thiacy-clodec-4-ene 5-oxide (66a,b) was prepared via several steps frtm (/ ,/ )-l,6-dibromo-3,4-hexanediol. Upon treatment with butyllithium, a 4 1 mixture of isomeric sulfoxides (66a and 66b) undergoes smooth cyclizadon to give a mixture of isomeric bicyclic sulfoxides (67a and 67b) in the same 4 1 ratio as the starting material, suggesting that the cyclizadon is essentially stereospecific. The major isomer (67a) is reduced with PCb to a sulfide (68) from which the desired (70) is derived via a thiaoctaline (69 heme 16). 

Reviews on the isopavine alkaloids have appeared dealing with various synthetic approaches and with that using lead tetra-acetate oxidation in particular/ The preparation of a number of argemonine analogues (47) by transannular addition of various biogenic amines, e.g. 5-methoxytryptamine to the dione (48), has been reported/""... 

Transannular additions by nucleophiles tend to occur with the larger carbocy-cles due to their increased flexibility, or in polycyclic compounds where reactive centers are forced into close proximity. 

In electrophilic addition reactions, transannular participation by an oxirane to form an oxonium ion occurs in medium-ring cycloalkenes. Thomas first investigated this transannular addition in epoxide 73 [86]. Treatment with iodine gave iodinated bicyclic ethers 74 and 75, Eq. 58. 

Diaryl-1,3-butadienes are obtained from ArCOMe directly by the reaction with Sml2 and AC2O in refluxing THF. ° Transannular addition of ketyl species generated from meso-cyclic ketones to a double bond is quite efficient. 

The elaboration of a polyunsaturated 5 9-fused ring system based on transannular addition of an alkenyllithium species to a triple bond following the Br—Li exchange of a bromoalkene is clean and elegant. 

Another transannular C-C bond formation reaction which starts with the attack of an electrophile at the triple bond is the formation of bityclic systems from tyclic diynes shown in Scheme 8-13, where H2SO4 induces the transannular addition of H2O to a cyclic diyne... 

Photolysis of (173) gave (174) by electrocyclic ring opening, followed by transannular addition of methanol to give (175). Addition-elimination of methanol to (174) gave (176) <84JOC587>. 

By transannular addition of sulfur dichloride to 9-oxabicyclo[3.3.1]nonan-2,6-diene... 

Transannular addition of sulfur dichloride to 9-azabicyclo[3.3.1]nona-2,6-dienes (42 N-formyl 9l 44 N-phenylsulfonyl 94 and 62 N-tolylsulfonyl p 3i, 32)j applied as an entry to the 2-thia-6-aza-adamantane system. The chlorine atoms in 91 were easily exchangeable with sodium iodide in boiling diethyl ketone (-> 92, 82%)" or with silver acetate in acetic acid (- 93, 70%)" resp. Under analogous reaction conditions the dichloride 94 was transformed into the diacetate 95 (95%) " LiAlH4-reduction of the diacetate 93 yielded 74% of N(6)-methyl-4 8 -dihydroxy-2-thia-6-aza-adamantane (97). The C(4) and C(8)... 

Sheradsky and Moshenberg attempted the preparation of (88) by electrocychc ring opening of the dione (89). Irradiation of (89) did indeed give the triazonine (M), but this was too reactive to be isolated. When the irradiation was conducted in dichloromethane solution, (88) rearranged to (90), but in methanol, transannular addition of the solvent to (88) occurred, leading ultimately to a mixture of (91) and (92) (Scheme 2) <84JOC587>. 

LI), 6-cyanotetracyclo(3.2 1.1.0)nonane, is isolated in 95% yield [with bis(acrylonitrile)-nickel as catalyst]. This is the first case of a transition metal-catalyzed transannular addition. It may be formulated according to Fig. 9 and provides a good example of a tr-complex multicenter process. 

Compound (LXVI) is particularly interesting as it undergoes a 1,7 addition with tetracyanoethylene. This transannular addition is possible since the opposite pairs of double bonds in (LXVI) parallel each other at a distance of only about 2.7 A, which must lead to appreciable ir-orbital interaction 105). In the presence of acetylene, with Ni(CO)2 2P(OC6H5)3 as the catalyst, a co-cyclopolymerization of allene to 3,5- and 3,6-dimethylene-cyclohexene (LXVII) and (LXVIII), respectively, is possible (106). With nickel acetylacetonate as catalyst, (LXVII) and 3,5,7-trimethylenecyclo-octene (LXVIII) are produced in 45% and 5% yield respectively. 106). This reaction makes exo-methylene cyclic compounds which are unsaturated easily accessible. The chemistry of (LXVII) has been studied in some detail 107). 

With the exception of the above routes, other reported preparations of these heterocycles followed the more conventional routes, such as intramolecular displacement by a thiolate ion or other nucleophilic sulphur function, intramolecular addition of a thiol radical to a carbon-carbon double bond, and transannular addition of SClg to dienes. 

Transannular additions of sulphur dichloride to cyclic dienes continue to be used as a route to bi- and poly-cyclic sulphur-containing rings. Ilie initial product (20) from the addition of SCI2 to cyclo-octa-l,S-diene has been converted into 2,6-diketo-9-thiabicyclo[3,3,l]nona-3,7-dienc. When (20) was heated with collidine the conjugated diene (21) was obtained. This product was suggested to arise via sulphur participation in the elimination process [see (22)] since neither the sulphoxide nor the sulphone underwent... 

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