1.3- Cycloheptadiene, 1,4-addition

Diacetoxylation of various conjugated dienes including cyclic dienes has been extensively studied. 1,3-Cyclohexadiene was converted into a mixture of isomeric l,4-diacetoxy-2-cyclohexenes of unknown stereochemistry[303]. The stereoselective Pd-catalyzed 1,4-diacetoxylation of dienes is carried out in AcOH in the presence of LiOAc and /or LiCI and beiizoquinone[304.305]. In the presence of acetate ion and in the absence of chloride ion, /rau.v-diacetox-ylation occurs, whereas addition of a catalytic amount of LiCl changes the stereochemistry to cis addition. The coordination of a chloride ion to Pd makes the cis migration of the acetate from Pd impossible. From 1,3-cyclohexadiene, trans- and ci j-l,4-diacetoxy-2-cyclohexenes (346 and 347) can be prepared stereoselectively. For the 6-substituted 1,3-cycloheptadiene 348, a high diaster-eoselectivity is observed. The stereoselective cij-diacetoxylation of 5-carbo-methoxy-1,3-cyclohexadiene (349) has been applied to the synthesis of dl-shikimic acid (350). 

The 1,4-oxidation has also been extended to the use of alcohols as nucleophiles45. By performing the reaction in an alcohol as the solvent with Pd(OAc)2 as catalyst and p-benzoquinone as the oxidant, a 1,4-dialkoxylation was obtained (equation 17). It was essential to add a catalytic amount of acid to get a reaction. The reaction is highly regio-and stereoselective and 1,3-cyclohexadiene and 1,3-cycloheptadiene afforded exclusively 1,4-yyw addition products (Table 1). 

It was also found experimentally that the rhodacyclohexenes 27a and 27b can be identified by H NMR when the siloxy-substituted VCP 14 is treated with a stoichiometric amount of [RhCKCO lz (Scheme 16). Addition of DMAD to the mixture of rhodacycles 27a and 27b gives the expected cycloheptadiene 28.47... 

It was concluded from the formation of a dimer that 598 emerged by a DMS reaction in addition to a bicyclo[1.1.0]butane derivative [248]. The azacydoheptatetraene 599, trapped in an argon matrix kept at -261 °C, was observed by IR spectroscopy after photolysis of 3- and 4-diazomethylpyridine [249]. According to quantum-chemical calculations, the protodebromination of the respective bromodihydrodiazepi-nium ions is believed to proceed via the l,4-diaza-5,6-cycloheptadienes 600 and 601 as intermediates [169, 250],... 

Selenosulfonylation of olefins in the presence of boron trifluoride etherate produces chiefly or exclusively M products arising from a stereospecific anti addition, from which vinyl sulfones can be obtained by stereospecific oxidation-elimination with m-chloroper-benzoic acid134. When the reaction is carried out on conjugated dienes, with the exception of isoprene, M 1,2-addition products are generally formed selectively from which, through the above-reported oxidation-elimination procedure, 2-(phenylsulfonyl)-l,3-dienes may be prepared (equation 123)135. Interestingly, the selenosulfonylation of butadiene gives quantitatively the 1,4-adduct at room temperature, but selectively 1,2-adducts at 0°C. Furthermore, while the addition to cyclic 1,3-dienes, such as cyclohexadiene and cycloheptadiene, is completely anti stereospecific, the addition to 2,4-hexadienes is nonstereospecific and affords mixtures of erythro and threo isomers. For both (E,E)- and ( ,Z)-2,4-hexadienes, the threo isomer prevails if the reaction is carried out at room temperature. 

However, the reaction of 1,3-cycloheptadiene is less regioselective. Isoprene and E,E-2,4-hexadiene afford 1,2-/1,4-adducts in ratios of 87 13 and 83 17, respectively. The high selectivity for 1,2-addition (>95%) to 1,3-pentadiene is opposite to the corresponding oxymercuration of the same diene, which has been reported159 to give mainly 1,4-adducts. The different regiochemistry has therefore been explained by assuming that sulfomercu-ration occurs under kinetic control whereas oxymercuration occurs under thermodynamic control. 

The photochemical behavior of cyclohexa-1,3-dienes113,114 differs from that of cycloheptadiene in that another pathway, that of ring opening, is available to the excited molecule in addition to the formation of the bicyclo[2.2.0]hexene system. This is reflected in the behavior of the corresponding heterocyclic derivatives. 

Given that nucleophile addition to (dienyl)Fe(CO)3 complexes proceeds stereospecifically trans to the metal, the question arises as to whether this can be used to control relative stereochemistry during multiple functionalization of cyclohexadienes and cycloheptadienes. A hypothetical example is shown in Scheme 29, where nucleophile addition is followed by a second hydride abstraction, or its equivalent, to generate a substituted dienyl complex. Addition of a second nucleophile, assuming steieocontrol from the metal, would generate a disubstituted derivative with defined relative stereochemistry. 

Double functionalization appears to be quite general, since a variety of 5-substituted cycloheptadiene-iron complexes are readily converted to 6-substituted cycloheptadienyliron systems, which in turn undergo regio- and stereo-controlled nucleophile addition.23... 

A solution of dibenzo[a,e]cycloheptadiene in anhydrous xylene is added in a dropwise fashion with stirring to a suspension of sodium hydride in refluxing anhydrous xylene. The mixture is heated at reflux for two hours with continual agitation and there is then added dropwise a solution of 2-methyl-3-dimethylaminopropyl chloride in an equal volume of xylene. The mixture is then heated for fifteen hours, after which time it is cooled and decomposed by the cautious addition of ice water. The layers are separated and the aqueous layer extracted with ether. The combined organic layers are next extracted with 10% hydrochloric acid and the acidic extracts then rendered alkaline by the addition of ammonium hydroxide. The precipitated oil is extracted three times with chloroform. The chloroform extracts are dried and concentrated in vacuo, the residue being distiiled to yield the product. 

Rearrangement of (7) at -10 to 30 C (Table 1, vide supra) provides quantitatively cis-6,7-dimethyl-1,4-cycloheptadiene (10). Furthermore, prolonged heating of (11) at 178 C produces, in addition to the trans isomer (12), the same sigmatropic rearrangement product (10 Scheme I)." Other studies have shown that thermolyses (178 C, 4.2 h) of substrates (24) and (25) give, in quantitative yields, the epimeric cycloheptadienes (10) and (27), respectively." Presumably, these transformations proceed by way of the corresponding cis-l,2-di(l-propenyl)cyclopropanes (7) and (26). °... 

Early synthetically oriented divinylcyclopropane-cycloheptadiene rearrangements were performed with hydrocarbons and were in part due to the interest in syntheses of marine brown algae constituents. The preparation of ectocarpene is displayed in equation 164. The corresponding divinylcyclopropanes have either been constructed by Wittig methodology or, as in the case shown, by addition of diazoalkanes to apt polyenes followed by photolysis or thermolysis . 

Cp2TiCl2 reacts with MgCIPr1 in the presence of cycloheptatriene to give 73-cycloheptadienyltitanium isomers (Scheme 491), which undergo in situ addition to aldehydes to produce a mixture of 1,3- and 1,4-cycloheptadienyl alkyl (aryl) carbinols. The reaction opens a simple way to functionalized 1,4-cycloheptadienes, some of which are closely related to biologically active compounds.1159... 

Lallemand s group has also investigated an alternative route to the crucial aminocycloheptanone intermediate (46) via a Diels-Alder addition between an acylnitroso derivative (44) and a protected polyhydroxy-cycloheptadiene (45) [56]. Due to an inability to remove the allyl groups chosen for protection of the hydroxyl functionality, this approach has yielded a propyl ether derivative of calystegine B2 other protecting groups which can be removed with more facility should render the parent alkaloid accessible. 

Transition metal (Cr, Mo) carbene complexes, e.g. 28, 30, 32, participate in additions to dienes and diene-tethered acetylenes with concomittant generation of divinyl-cyclopropanes, which undergo ring expansion under the reaction conditions to cycloheptadiene-annulated ring systems such as 29, 31 and 33. 

Amino alkenols have been prepared by palladium-catalyzed chloroacetoxylation and allylic amination of 1,3-dienes. 1,4-Acetoxychlorination is stereo specific and cyclic dienes give an overall c/5-l,4-addition 2. Acetoxychlorination of 6-acetoxy-l,3-cycloheptadiene afforded only one isomer as shown in equation 8. Sequential substitution of the allylic chloro group can occur with either retention or inversion, thereby allowing complete control of the 1,4-relative stereochemistry (equation 9). 

Without the disadvantage of using diazo compounds in the first step, Wenkert s latest monoterpenoid syntheses would be most efficient approaches, and in any case represent novel routes to well-known materials. Nezukone (754) was the result of examining the reaction between butadiene and diazopyruvic ester catalyzed by rhodium tetraacetate. The major product of the addition was the cyclopropane 758 (Scheme 62). It was known that divinylcyclopropanes could be thermolyzed to cycloheptadienes (Vol.4, p.537, Ref.600). The Wittig product from 758 thus gives a cycloheptadiene, and subsequent steps are shown in the scheme. The last step involves Grignard addition to the ester function of the enolate, then loss of water and redistribution of the double bonds.(Further examples of the use of diazo compounds will be found under perillene in the section on furans.)... 

The thermolytic transformation of tra s-1,2-divinylcyclopropane (4) into 1,4-cycloheptadiene (2) probably proceeds via the pathway shown in equation (2). Homolytic cleavage of the cyclopropane ring of (4) provides the resonance stabilized diradical (5), which, in addition to reverting to (4), can undergo bond rotation and subsequent ring closure to give cis-l,2-divinylcyclopropane (1). The latter substance then rearranges, by way of conformation (lb), into (2). 

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