1.4- Cycloheptadiene synthesis

Scheme 8.13 Cycloheptadiene synthesis through Pd-catalyzed bisallylic substitution.

Scheme 8.15 Cycloheptadiene synthesis through Ni-catalyzed three-component coupling.

Scheme 8.17 Cycloheptadiene synthesis through Rh-catalyzed [1,5] C-C bond migration.

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 wM-diacetate 363 can be transformed into either enantiomer of the 4-substituted 2-cyclohexen-l-ol 364 via the enzymatic hydrolysis. By changing the relative reactivity of the allylic leaving groups (acetate and the more reactive carbonate), either enantiomer of 4-substituted cyclohexenyl acetate is accessible by choice. Then the enantioselective synthesis of (7 )- and (S)-5-substituted 1,3-cyclohexadienes 365 and 367 can be achieved. The Pd(II)-cat-alyzed acetoxylactonization of the diene acids affords the lactones 366 and 368 of different stereochemistry[310]. The tropane alkaloid skeletons 370 and 371 have been constructed based on this chemoselective Pd-catalyzed reactions of 6-benzyloxy-l,3-cycloheptadiene (369)[311]. 

Metal-mediated and -catalyzed [3 + 2 + 2]-higher-order cycloaddition reactions have also proved to be viable and mechanistically novel methods for the synthesis of seven-membered rings. The reported [3 + 2 + 2]-cycloadditions of allyliridium (Equation (30)),139 -allylcobalt (Scheme 47),140 and allylmanganese (Equation (31 ))141 complexes with alkynes involve the reaction of preformed allylmetal complexes with two separate alkynes, leading to a cycloheptadiene-metal complex. 

Rhodium(II) (iV-dodecylbenzenesulfonyl)prolinate has been found to act as an effective catalyst for the enantioselective decomposition of vinyldiazoacetates to c -divinylcyclopropanes. Combination of this process with a subsequent Cope rearrangement has resulted in a highly enantioselective synthesis of a variety of cycloheptadienes containing multiple stereogenic centres (see Scheme 40). The tandem... 

Oxygenated dienes are exceptional substrates for vinylcarbenoids [78]. In order to avoid side-products derived from zwitterionic intermediates, nonpolar solvents are typically employed. A short synthesis of nezukone 57 highhghts the utiHty of the [3-1-4] cycloaddition for the synthesis of tropones (Scheme 14.4). The cycloaddition between the oxygenated butadiene 55 and 52 generates the cycloheptadiene 56 in 67% yield [78]. Treatment of 56 with Meli followed by acid-induced dehydration completes a very short synthesis of nezukone 57. 

The vinylcarbenoid [3-1-4] cycloaddition was applicable to the short stereoselective synthesis of ( )-tremulenolide A 73 and ( )-tremulenediol A 74 (Scheme 14.7) [81]. The key step is the cyclopropanation between the cyclic vinyldiazoacetate 69 and the functionalized diene 70, which occurs selectively at the ds-double bond in 70. Because of the crowded transition state for the Cope rearrangement of the divinylcyclopropane 71, forcing conditions are required to form the fused cycloheptadiene 72. The stereo-... 

Intramolecular cyclopropanation using diazoesters is a powerful synthetic tool. Diazoesters are readily prepared from the corresponding alcohol via House s methods56-57. Numerous examples using the application of this transformation in synthesis have been reported. These include the potent synthetic pyrethroid NRDC 182 (22)58, (1 R)-( )-cis-chrysanthemic acid (23)59, the highly strained bicyclic system 2460, antheridic acid 2561,62 and cycloheptadiene 26 (equations 33-37). 

Photocyclization of 1,3-cycloheptadienes is a particularly efficient process, since ring fission is not possible. The photocyclization of 1,3-cycloheptadienes in conjunction with a recently developed synthesis of substituted 1,3-cycloheptadienes (159) constitutes an important synthetic entry to the bicyclo[3.2.0]heptane series. Irradiation of 1,3-cycloheptadiene (Formula 361) gives the bicyclic photoisomer (Formula... 

Sertraline [60], chiral 1,4-cycloheptadienes [61], and select cyclopentenes [62] have been prepared by using these catalysts and vinyldiazocarboxylates, and this approach has also been applied to the enantioselective synthesis of functionalized tropanes [63] and of the four stereoisomers of 2-phenylcyclopropane-l-amino acid [64]. 

A concentrated solution of LiCl04 in EtzO is effective in the allylation of silyl enolates with allyl alcohols and acetates.310 The LiClCL-promoted reaction with silyl enolates enables ring opening of 8-oxabicyclo[3.2.1]octa-2,6-dienes to highly functionalized 1,4-cycloheptadienes, which can be further manipulated for use in natural product synthesis (Equation (83)).311... 

Removal of —Fe(CO)z (6, 624). The cation of cycloheptadiene has found limited use in synthesis because of limited stability. However, the iron tricarbonyl... 

The complex functions as a convenient source of the tricarbonyliron moiety by displacement of the unsaturated ketone. For example, reaction with 1,3-cycloheptadiene results in a 78% yield of (//-l,3-cycloheptadiene)tricar-bonyliron. More importantly, it may be used in syntheses of tricarbonyl-(diene)iron complexes where the iron carbonyls are not satisfactory. Several complexes of sensitive heptafulvenes have been prepared in this way, and the reagent has been used in the synthesis of tricarbonyliron complexes of several steroids. 

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