Cycloheptene, reactions

Cyclic alkenes give different regioisomers depending on the reaction conditions owing to double bond isomerization caused by syii elimination of Pd—H species and its readdition. The following three reaction conditions were tested for the reaction of cycloheptene (35)[18,38] ... 

Oxime 26 was prepared from 5,ll-dihydro-dibenzo[a,d]cyclohepten-10-one. The Hoch-Campbell reaction of 26 with 3-dimethylaminopropylmagnesium bromide produced aziridine 27 in 46% yield after acidic workup. Extension of the Hoch-Campbell reaction to steroids has also been reported. Thus, treatment of 3(3-hydroxy-5-pregnen-20-one oxime (28) with methylmagnesium iodide furnished a mixture of diastereomers, 20ot/20P,21-imino-20-methyl-5-pregnen-3P-ol (29) in a 50% combined yield and a 3 1 ratio. On the other hand, homo-adamantan-4-one oxime (30) was transformed to homo-adamantano[4,5-b]-2 -ethylaziridine (31) in 76% yield upon the action of... 

Phthalic anhydride is reacted with phenylacetic acid to form 3-benzylidenephthalide which is then hydrogenated to 2-phenethylbenzoic acid. Conversion to the acid chloride followed by intramolecular dehydrochlorination yields the ketone, 5H-dibenzo[a,d] cyclohepten-5-one. The ketone undergoes a Grignard reaction with 3-(dimethylamino)propyl chloride to give 5-(7-dimethylaminopropylidene)-5H-dibenzo[a,d] cycloheptene. 

To 3.8 g of 2-methyl-3-(10,11-dihydro-5H-dibenzo[a,d] cycloheptene-5-ylidene)-1-pyr-roline, there were added 8 g of ethyl iodide. This mixture was placed into a closed vessel and heated at 80°C in a water-bath for one hour. After completing the reaction, the reaction mix-... 

Ethyl-2-methyl-3-(10,11) -dihydro-5H-dibenzo [a,d] cycloheptene-5-ylidene)-1 -pyrrolinium iodide (4.7 g) was dissolved in 7 cc of methanol. To this solution there were added 1.4 g of sodium boron hydride within about 80 minutes with stirring and stirring of the solution was continued for two hours to complete the reaction. The reaction mixture was acidified with 10% aqueous hydrochloric acid solution and then the methanol was distilled off. The residual solution was alkalized with 20% aqueous sodium hydroxide solution and extracted with ether. The ether layer was dried over magnesium sulfate and the ether was distilled off. The resulting residue was further distilled under reduced pressure to yield 2.0 g of 1-ethyl-2-methyl-3-(10,11 ) dihydro-5H-dibenzo[a,d]cycloheptene-5-ylidene)pyrrolidine (boiling point 167°C/4 mm Hg.). 

Scheme 77 RRM reactions of enantiopure cycloheptenes leading to dihydrocuscohydrine (390) [161], anaferin dihydrochloride (393) [162], and indolizine 167B (397) [163]...

The combination of BSTP 1949 with SnCl4 converts olefins such as cyclopen-tene 1991a, cyclohexene 1991b, or cycloheptene 1991c into their trans-l,2-chloro-hydrins 1992 a-c in 74, 85 and 92% yield, respectively [168]. Reaction of the cyclic... 

That the high degree of torsional and other types of strain inherent in the triplet states or trans conformers of cyclohexene and cycloheptene may be responsible for their photochemical behavior is suggested by the reactions of compound (50), a moderately twisted olefin according to molecular models. Compound (50) quantitatively yields bicyclo[3.3.1]non-l-yl acetate (51) within 15 sec after being dissolved in glacial acetic acid(83> ... 

The following example completes the section of threefold anionic domino processes initiated by a SN-type reaction. As discussed earlier in Section 2.2, the reaction of a five-membered cyclic phosphonium ylide with enones, a, 3-unsaturated esters, and a, 3-unsaturated thioesters provides cycloheptene or hydroazulene derivatives in a domino Michael/intramolecular Wittig reaction. This sequence... 

However, as illustrated in Scheme 2.112, the reaction of ylide 2-490 with 4-hexen-3-one (2-491) did not lead to the expected cycloheptene, but to the cyclopropane derivative 2-493 in 98% yield by a simple addition of the ylide to 2-491 to give 2-492... 

In another conceptually novel [5 + 2]-process, Tanino and co-workers synthesized cycloheptene derivatives by stereoselective [5 + 2]-cycloadditions involving hexacarbonyldicobalt-acetylene complexes as the five-carbon component and enol ethers as the two-carbon component (Schemes 22 and 23).60 61 The role of the dicobalthexacarbonyl complex is to facilitate formation and reaction of the propargyl cation putatively involved as an intermediate in this reaction. The dicobalthexacarbonyl moiety can be removed using various conditions (Scheme 24) to provide alkane 60, alkene 62, and anhydride 63. 

In addition to tropones, a few tropolones have been synthesized by reactions similar to those given in Scheme 2 and Table I. Hydroxyl substituents vicinal to carbonyl groups have been generated by hydrolysis of dibromo intermediates of type 5a (78BCJ3579) and by dehydrogenation of fused cyclohepten-3,4-diones [55LA(595)203] or their monoximes [70JPR(312)466] (by Pd-charcoal or spontaneously, respectively). 

Hoveyda et al. reported a novel method for synthesizing of chromene 71 by ROM-RCM of cycloalkene 70 bearing the phenyl ether at the 3-position [Eq. (6.48)]." ° The yield is improved when the reaction is carried out under ethylene gas. In the case of cyclopentene 70a (n = 0) or cyclohexene 70b (n = 1), the yield is poor because the starting cycloalkene is in a state of equihbrium with the product and a thermodynamic product should be formed under these reaction conditions. They obtained enantiomeric ally pure cycloheptene derivative (5)-70e using zirconium-catalyzed kinetic resolution of 70e developed by their group, and chromene 71c was synthesized as a chiral form via ROM-RCM using lb [Eq. (6.49)] ... 

Inaba and coworkers reported that a Ti-BINOL complex is an effective catalyst for the desymmetrization of epoxide 44 using primary amines as nucleophiles. Of significant note is the efficiency of this reaction, with only 1 mol% catalyst necessary to attain high yields and selectivities [Eq. (10.11)]. Unfortunately, this epoxide is uniquely effective in this reaction. Cycloheptene oxide, dihydrofuran oxide, and an acyclic version of 44 each provided negligible yields under these reaction conditions ... 

With this revision in our original plans, both alkenes and allenes were found to undergo efficient cycloadditions to produce cyclooctenone products in a new [6+2] cycloaddition process. This novel cycloaddition has been shown to proceed efficiently with alkenes tethered with sulfonamide, ether, or geminal diester Hnkers (Tab. 13.15, see page 294). Isomerization of the olefin, a potential competing reaction in this process, is not observed. Methyl substitution of either alkene in the substrate is well tolerated, resulting in the facile construction of quaternary centers. Of mechanistic importance, in some cases cycloheptene byproducts were isolated from [6+2] cycloaddition reactions in addition to the expected cyclooctenone products (that is, entries 3 and 4). 

Two suggested methods of nortriptyline synthesis are based on the N-demethylation of amitriptyline. The third way utilizes the reaction of methylamine with 5-(3-bromopropyli-den)-10,11 -dihydro-57f-dibenz [a,d]cycloheptene (7.1.18). 

Although the catalytic reactions described above involve mononuclear Rh and Rh complexes, dinuclear Rh compoimds have also been studied as catalyst precursors in oxygenation reactions. The system [Rh2(p.-OAc)4]/ f-BuOOH is effective in the oxidation of cyclic alkenes such as cyclopentene, cyclohexene and cycloheptene, mainly to o, /i-unsaturated ketones and allylic acetates, but with poor yields (Eq. 4) [30,31]. 

It is generally agreed that alkenyl hydroperoxides are primary products in the liquid-phase oxidation of olefins. Kamneva and Panfilova (8) believe the dimeric and trimeric dialkyl peroxides they obtained from the oxidation of cyclohexene at 35° to 40° to be secondary products resulting from cyclohexene hydroperoxide. But Van Sickle and co-workers (20) report that, The abstraction/addition ratio is nearly independent of temperature in oxidation of isobutylene and cycloheptene and of solvent changes in oxidations of cyclopentene, tetramethylethylene, and cyclooctene. They interpret these results to support a branching mechanism which gives rise to alkenyl hydroperoxide and polymeric dialkyl peroxide, both as primary oxidation products. This interpretation has been well accepted (7, 13). Brill s (4) and our results show that acyclic alkenyl hydroperoxides decompose extensively at temperatures above 100°C. to complicate the reaction kinetics and mechanistic interpretations. A simplified reaction scheme is outlined below. 

This finding is rooted in the DMSO promoter and Krafft s demonstration that a suitably positioned sulfur moiety tethered to the PK precursor increases the reaction efficiency. The reaction conditions with these promoters generally require much higher reaction temperatures than that with oxidative promoters, and complete the reaction in substantially shorter periods to give high chemical yields. Moreover, the sulfur additive promotes the intermolecular PKR with even unstrained and less reactive olefins. A prominent example is the reaction between phenylacetylene and cycloheptene (Equation (3)). ... 

Antidepressant activity is retained when the double bond in the cycloheptene ring is replaced by a fused cyclopropane. The starting material for this compound is obtained by the reaction of unsaturated ketone (24-6) with dichlorocarbene... 

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