Bicyclic 1,2-dibromide

The classical Hunsdiecker reaction was utilized in the laboratory of P.J. Chenier for the preparation of a highly strained cyclopropene, tricyclo[3.2.2.0 " ]non-2(4)-ene. The Diels-Alder cycloaddition was used to prepare the bicyclic 1,2-diacid, which surprisingly failed to undergo the Cristol-Firth modified Hunsdiecker reaction, most likely due to the unreactive nature of the diacid mercuric salt. However, the classical conditions proved to work better to afford the bicyclic 1,2-dibromide in modest yield. Treatment of this dibromide with f-BuLi generated the desired strained cyclopropene, which was trapped with diphenylisobenzofuran (DPIBF). 

That the allene route should always be kept in mind, though, is demonstrated for example by 6,6-dibromobicyclo[3.1. OJoctane and 8,8-dibromo-bicyclo[5.1.0]-octane, respectively. When these bicyclic dibromides are reacted with methyl-lithium at room temperature they are evidently converted into the corresponding cyclic allenes since these intermediates may be either trapped by reagents like styrene or dimerize, [2+2]adducts being formed in both cases. 

Another example of the modification of the initial Diels-Alder adduct is shown in Scheme 82. Bicyclic dibromide 477 provides with PTAD the corresponding cycloadduct 478, which after debromination affords 479. Further treatment with 2-pyrone proceeds with the evolution of carbon dioxide to give cycloadduct 480, which in the usual way provides 481 (72JA3658). Intermediate 479 can be photochemically isomerized to give a diazabas-ketane derivative 482, which then, by a well-known sequence, can provide diazabasketane 483 (74JA7454 77JA1524). The Ag -catalyzed rearrange-... 

Methanolysis of bicyclic dibromide 52 with MeOH in the presence of AgC104 gives trans product 53 [30]. 

Thus, as expected from earlier work 36,37), the dioxabicyclization proceeds with inversion of configuration at the 3-position of the m-2-frans-3-dibromide 30, the stereochemistry at the 2-position being unaffected. However, experiments with individual diastereoisomers unexpectedly showed that the franj-2-m-3-dibromide 31, also reacts with silver trifluoroacetate, albeit less efficiently, to give the same bicyclic peroxide. We feel that this probably proceeds via an isomerisation (Eq. 25). 

Reaction of 1,3-cyclooctadiene with N-bromosuccinimide results in the formation of dibromides 82 and 83, treatment of which with silver acetate in acetic add provides the acetates 84 (80 %) and 85 (20 %).13 The bicyclic acetate can readily be separated and transformed to the corresponding enone. 

For the cyclooctatetraene (COT)-bicyclo[4.2.0]octa-2,4,7-triene system (125)-(126), earlier studies using an indirect method afforded an equilibrium composition at 100 C containing 0.01% of the bicyclic form (126) (AG = 6.8 kcal mol" less stable). The bicyclic form (126) has been prepared, however, by low-temperature dehalogenation of dibromide (127) and found to rearrange to COT at 0 °C ( a = 18.7 kcal mol" ). " Recently, a high-temperature thermal trapping technique has been utilized to assess more completely the transformation between (126) and (125) in a quantitative manner. ... 

An alternative for the use of 374 in functionalization reactions of l,3-dithiole-2-thiones involves using the tetraethylammonium salt of the zinc complex 413. Its versatility was demonstrated in the synthesis of heterocycles such as the bicyclic 416 and the tricyclic 417 via the dialkylation reaction of 413 with dibromides 414 and 415, respectively (Scheme 57) <1998S1615>. 

A formal total synthesis of ( )-morphine has been achieved by adopting the above synthetic route (Scheme 18). The tetrahydropyridine 91, prepared from the reaction of A/ -methyl-4-piperidone with 2,3-dimethoxy-phenyllithium, followed by dehydration, was converted to the bicyclic en-amine 92 by treatment with the ylic dibromide. Kinetic protonation of 92 with perchloric acid gave the trans-fused immonium salt, which upon dissolution in methanol equilibrated to the thermodynamically prefered cis isomer 93. Treatment of 93 with diazomethane brought about the formation of the aziridinium salt 94, which was readily transformed into the a-amino aldehyde 95 by its oxidation with dimethyl sulfoxide. It is also worth noting that the Komblum oxidation of aziridinium salts leads to the construction of a-amino aldehydes efficiently. Lewis-acid-catalyzed cyclization of 95 afforded the morphinan carbinol 96 in 80% yield. Successive mesylation and reduction of the mesylate derived from 96 with LiBEtjH afforded morphinan (97) in excellent yield. In this instance, direct conversion of 93 to 97 by treatment with diazomethane gave approximately 1 % of the desired product. Lemieux-Johnson oxidation of 97 under acidic conditions furnished the ketone 98, which was previously transformed into ( )-morphine by Gates. In order to confirm the structure of 98, its conversion to the known... 

Ring closures to 2-oxa-6-aza-adamantanes starting from bicyclic dienes were also accomplished by hydroxybromination of the 9-aza-diene 62 with N-bromo-succinimide (-> 63 53%) and by reaction of the 9-oxa-diene 1 with N -dibromo-p-tolylsulfonamide (- 64 25%). Both dibromides were converted to 63 (raney-nickel/Hj), which itself by treatment with sodium in liquid ammonia, yielded unsubstituted 2-oxa-6-aza-adamantane (5S), also characterized as its hydrochloride 38 HCl and N-benzoyl-derivative 66. 

Tetrakis(trimethylgermyl)diphosphine has been prepared in quantitative yield by oxidatively coupling (Me8Ge)aPLi with ethylene dibromide. Methyl-lithium cleaves the Sn—P bond of (Me3Sn)sP to give the stannyl phosphide (Me3Sn)aPLi,-EtaO, whereas the tin rich bicyclic compound (84) results from McaSnHa and... 

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