Bicyclo octane ring formation

Bicyclo[3J.0]octane and Bicyclo[3.2.1]octane Ring Formation... 

The Weiss-Cook reaction entails the formation of c/5-bicyclo[3.3.0]octane ring systems from the condensation of 1,2-dicarbonyl compounds with 3-oxoglutarate diester derivatives. Decarboxylation of the immediate reaction product affords access to the parent carbon scaffold. 

When formation of either the five- or six-membered ring was possible for N-chloroamine 37, only the five-membered ring was conducive under the Hofmann-Ldffler-Freytag reaction conditions, forming exclusively 6-ethyl-6-aza-bicyclo[3.2.1]-octane (38). No 2-ethyl-2-aza-bicyclo[2.2.2]-octane (39) was observed. On the other hand, 2-methyl-2-aza-bicyclo[2,2.2]octan-6-one (41) was installed by UV irradiation of a solution of A -chloroamine 40 in TFA. Ironically, when the ketone functionality on 40 was protected as its ethylene ketal group, the resultant steric interactions completely prohibited the classic Hofmann-Loffler-Freytag reaction. 

Similar procedures are also successful in the construction of cyclobutane rings in other stereochemical environments, including the formation of bicyclo[3.1.1]heptane (67)and bridged tricyclic systems such as (68), (69) ° and (70). ° A variety of annelated cyclobutanes have been prepared by the photochemical procedure as above, yields are sometimes poor or only moderate. Examples include bicy-clo[2.1.0]pentanes (71), °° bicyclo[2.2.0]hexanes (72)"° and cyclobuteno aromatics (e.g, 73), " o-nor-steroids e.g. 74)," A-bisnorsteroids" and triterpenes" as well as the highly strained tricyclo[4.2.0.0 ]octane system (75)," and the [4.4.4.5]fenestrane (76)." ... 

The bicyclic a-hydroxy acid 10a was obtained from the ring contraction of the 7,8-bis(trimethyl-siloxy)bicyclo[4.2.0]oct-3,7-diene (product of an acyloin cyclization) either by selective bro-mination at — 40 °C and subsequent hydrolysis or by simple autoxidation under an air stream. On further bromination at 20 °C and subsequent solvolysis in aqueous sodium hydroxide the hydroxycyclopropanecarboxylic acid 10a was transformed into 4-bromo-6-oxatri-cyclo[3.2.1.0 ]octane-7-carboxylic acid (11) by intramolecular cyclization, resulting from the addition of the c <7o-hydroxy group to the cyclohexene double bond. Formation of the product resulting from the addition of the carboxy group was not observed. ... 

As an alternative to a radical chain mechanism for this bromination, a cationic mechanism has been proposed for the reaction between 48 and A-bromosuccinimide. It involves attack of bromine at C6 of 48 leading ultimately to the cyclopropylmethyl cation A. This cation is a bromo derivative of tricyclic cyclopropylmethyl cation, which has been shown to be the common intermediate in the solvolysis of esters of tricyclo[3.2.1.0 ]octan-3-ol, endo- and exo-tricyclo[3.2.1.0 ]octan-4-ol and of cxo-bicyclo[3.2.1]oct-2-en-7-ol. It has been shown that under long-lived ion conditions at — 78 C such cations are the most stable species that are formed from bicyclo[3.2.1]oct-2-en-3-ol and from bicyclo[3.2.1]octa-2,6-dienes. In kinetically controlled reactions, which are postulated to proceed via cyclopropylmethyl cations a tendency can be seen towards formation of products retaining the cyclopropane ring. This case is achieved through loss of one of the protons at C4 of A. 

Transannular participation of n-bonds takes place in the solvolysis of esters of (Z)-cyclooct-3-enol to give bicyclic derivatives containing three-membered rings. Thus, acetolysis of 4-(4-bromophenylsulfonyloxy)cyclooctene followed by hydrolysis of the product mixture gave endo-and exo-bicyclo[5.1.0]octan-2-ol (1), in 39 and 13% yield, respectively. The predominant formation of the cntfo-bicyclooctanol is consistent with a concerted process. ... 

Consider now the cw-2,8-dimethyl-frawi-pyrrolizidine (13, X = N), with its trans-ring fusion and its gas-phase enthalpy of formation of —66.7 2.6 kJmoU. The enthalpy of formation of the corresponding hydrocarbon, 2,8-dimethyl-frawi-bicyclo[3.3.0]octane (13, X = CH) is estimated to be —126 kJ moU by assuming thermoneutrality of reaction 11. 

---