A -Cycloheptenone

Organometallic methods, with the possible exception of those involving the stoichiometric generation of enolates and other stabilized carbanionic species 140], have seldom been used in carbohydrate chemistry for the synthesis of cyclohexane and cyclopentane derivatives. The present discussion will not cover these areas. The earliest of the examples using a catalytic transition metal appears in the work of Trost and Runge [41], who reported the Pd-catalyzed transformation of the mannose-derived intermediate 22 to the functionalized cyclopentane 23 in 98% yield (Scheme 10). Under a different set of conditions, the same substrate gives a cycloheptenone 24. Other related reactions are the catalytic versions of the Ferrier protocol for the conversion of methylene sugars to cyclohexanones (see Chap. 26) [40,42,43]. 

Show how octane-2,7-dione might cyclize to a cycloheptenone. Explain why ring closure to the cycloheptenone is not favored. 

The reaction of 1-sulfanyl-substituted cyclopropyltriphenylphosphonium salts 15 and 17, in which both the donor and acceptor functions are located at same ring atom, with the enolate anion of -oxocarboxylates led to sulfanyl-substituted cyclopentenes as a result of opening of the three-membered ring and a subsequent intramolecular Wittig reaction. This method was applied to the construction of the hexahydroazulene system 18 by utilizing a cycloheptenone-based enolate as nucleophile. ... 

A cycloheptenone precursor to the (+)-Prelog-Djerassi lactonic acid has been synthesized stereoselectively from cyclohepta-1, 3-diene using a nucleophilic addition-reactivation-nucleophilic addition sequence on iron complexes to introduce the required... 

Another method enables conversion of sUyl ethers 62 into the corresponding cycloheptanones 63 (Scheme 19) [16, 17]. In this case, a tandem oxidative ring expansion and addition promoted by HTIB (Phl(OH)OTs) occurs through the formation of a cycloheptenone intermediate. The authors also describe the formation of a bicyclic cyclooctanone (n = 2) in this process. 

A somewhat lengthier but nonetheless unique stepwise transformation of nerolidol to cedrene has been described by Demole et al. The reaction of nerolidol with N-bromosuccinimide and dehydrobromination furnishes a cycloheptenone (A) which has been converted to the spirotriene (B). The latter may be cyclized to 2,8-cedradiene (C) and thence to a mixture of a -cedrene and 2-epi-oi-cedrene. 

Bromocyclohept-2-en-l-one (40) should be convertable to cycloheptenone (41) by hydrogenolysis of the bromine atom. Thus the process (34) - (41) provides a general method for conversion of symmetrical cyclohexanones to cycloheptenones. 

Johnson s procedure can be used to prepare A-homo-4a-ene-3-keto steroids or, more generally, any 7-membered ketone having an olefinic linkage. For simple saturated 6-ring ketones, Parham s procedure offers an alternate approach to the preparation of cycloheptenones. 

Posner recently reported a very simple and fast way to activate epoxides towards nucleophilic opening by ketone lithium enolate anions by use of BF3 Et20 (1 equiv.) [73]. The application of this procedure to the nucleophilic opening of propene oxide with the lithium enolate of 2-cycloheptanone, obtained by the conjugate addition of trimethylstannyllithium to 2-cycloheptenone, afforded the stan-... 

The addition of lithium dipropylcuprate-boron trifluoride to 4-methyl-2-cycloheptenone produced a d.r. (trans/cis) of 83 17, and almost the same degree of diastereoselectivity was obtained in the case of 5-methyl-2-cycloheptenone23. However, 6-methyl-2-cycloheptenone gave a d.r. (trans/cis) ratio of 37 6323. 

A broad study of aluminum chloride-induced cycloadditions of cyclopente-nones, cyclohexenones and cycloheptenones with 1,3-butadiene (1), isoprene... 

The mechanism for formation of the cycloheptenone is exactly the same as discussed in the book. After a Diels-Alder reaction, the enol ether is hydrolyzed to the ketone by an acid-catalyzed mechanism. 

Similarly, the [3-1-4] annulation of the E- and Z-isomers of /3-hetero-substituted acryloylsilanes 52 with lithium enolates of a,-unsaturated methyl ketones 54 gave stereospecifically the c -6,7-cyclopentyl-5-trimethylsilyl-3-cycloheptenone 55 (equation 20). The stereospecificity in the annulation was explained by an anionic oxy-Cope isomerization of the 1,2-divinylcyclopropanediol intermediate 56, which was generated through the Brook isomerization of the initial 1,2-adduct (equation 20). 

Alkoxy-VCP 163 was found to be a very competent reagent in the intermolecular [5+2] cycloaddition (Tab. 13.12). With some minor optimization of the previous reaction conditions, namely the use of 1,2-dichloroethane (DCE) as solvent at a higher concentration (0.5 M) and reaction temperature (80 °C), the reaction was found to be complete in minutes in some cases with 0.5 mol% [RhCl(CO)2]2, while still providing good to excellent yields of cycloheptenone products. Significantly, reactive functionahty, including unprotected alcohols and carboxylic acids, is tolerated in the reaction. The reaction is also readily scaled, with comparable isolated yields over a 100-fold increase in scale. The formation of products in minutes is of consequence, as such reactions allow for the more time-efficient reahzation of synthetic goals. 

A synthesis of the 11-aryl-1 l-aza[5.3.1 ]propellan-2-one 29 was accomplished by the intermolecular cycloaddition of the cycloheptenone 26 with an aryl azide. The... 

The related dirhodium(II) a-caprolactamate (cap) complex [Rh2(p--cap)4] undergoes a one-electron oxidation process at quite a lower potential (11 mV) than the acetate complex (1170 mV). In agreement with the Kochi hypothesis, the a-caprolactamate complex has recently been found to be an exceptional catalyst for the allylic oxidation of alkenes under mild conditions. A wide range of cyclohexenes, cycloheptenes, and 2-cycloheptenone (Eq. 5) are rapidly converted to enones and enediones in 1 h with only 0.1 mol % of [Rh2( x-cap)4] and yields ranging from 60 to 90%, in the presence of potassium carbonate [34]. 

In an interesting fragmentation reaction, the hexahydroazocine (23) is formed by solvolysis of (22) in the presence of NaBHt in 94% yield (75TL2613). A related compound (24) can be prepared from 4-cycloheptenone oxime tosylate via the unsaturated lactam (25) (79JOC287). Whereas (25) adds bromine to the double bond, (24) undergoes a transannular reaction to give a 1-substituted pyrrolizidine (26). The latter type of reaction also occurs... 

In the presence of proton and/or Lewis acid and strong nucleophiles bicyclo[3.2.0]heptan-6-ones are converted to 3-substituted cycloheptanones (Table 15). Bicyclo[3.2.0]heptan-6-ones rearrange to give 3-iodocycloheptanones on treatment with iodotrimethylsilane. Zinc(II) iodide or mercury(II) halides as catalysts enhance the rate and the selectivity of the reaction.31 If a second, enolizable carbonyl group is present, an intramolecular alkylation may follow the ring enlargement under these reaction conditions.32 Consecutive treatment with tributyltin hydride/ 2,2 -azobisisobutyronitrile affords reduced, iodo-free cycloheptanones, whilst treatment with l,8-diazabicyclo[5.4.0]undecene yields cycloheptenones.33 Similarly, benzenethiol adds to the central bond of bicyclo[3.2.0]heptan-6-ones in the presence of zinc(II) chloride and hydrochloric acid under anhydrous conditions to form 3-(phenylsulfanyl)cycloheptanones.34... 

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