Cycloheptenone enolate

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 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). 

Ring expansion (7, 153-154). Details are available for expansion of cyclohexanone to 2-cycloheptenone via cyclopropanation of enol silyl ethers (equation 1). The report includes six other examples of this method yields range from 80 to 98%. In all cases the more highly substituted C C bond of the cyclopropane ring is cleaved by FeCI,.1... 

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]. 

The presumed Z-enoxysilane 28 undergoes rearrangement prior to warming to room temperature furnishing siloxy cycloheptadiene 29. Hydrolysis of silyl enol ether 29 yields (6S, 8/ )-cycloheptenone 7. 

Fig. 11.23. Ring expansion of cycloheptenone via a carbenoid intermediate. The elimination of LiBr from the carbenoid occurs with or is followed by a [12]-alkenyl shift. The enolate C is formed and, upon aqueous workup, it is converted to the ring-expanded cycloalkenone B.

Cycloheptane annelation (7, 212). The mixed cuprate 1 reacts with acid chlorides to afford vinylcyclopropyl ketones. Previously these ketones were prepared from aldehydes by condensation with l-lithio-2-vinylcyclopropane followed by oxidation (7, 192-193). These compounds are rearranged to 4-cycloheptenones on conversion to trimethylsilyl enol ethers, thermolysis, and hydrolysis. ... 

An alternative way to generate a divinylcyclopropane system takes advantage of enolizable carbonyl groups. Trapping of the enolate with trialkylsilyl chloride will usually create the second olefin unit required for a Cope rearrangement. The example of equation (172) demonstrates a sequence of high overall efficiency providing silyl enol ethers which have been hydrolysed to 4-cycloheptenones. The enol ethers should also be versatile intermediates for other transformations. 

It must be emphasized that no heterocyclization occurs and that the formation of the cycloheptenone involved the enolization of the carbonyl group of the methylcyclopropyl ketone. 

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. ... 

Substituted cycloheptenones 25 can be prepared by thermolysis of neat cyclopropyl silyl enol ethers 23 under an inert atmosphere, followed by hydrolysis of the resulting crude silyl enol ethers 24. This procedure is quite general for low molecular weight compounds. The enol ethers 23 are generated from either the cis- or trani-isomers of 22 and rearrange in excellent yields, albeit at different temperatures. 

ETHENYL-4-METHOXYCYCLOBUTENE-l,2-DIONE. This procedure also provides a convenient method for the preparation of DIMETHYL SQUARATE, an important intermediate. The synthesis of (lR, 6S, 7S )-4-(tert-BUTYLDIMETHYLSILOXY)-6-(TRIMETHYLSILYL)BICYCLO-[5.4.0JUNDEC-4-EN-2-ONE is representative of a general protocol for the construction of cycloheptenones by a [3 + 4] annulation. The method features the addition of a lithium enolate to an acryloyl silane to give a 1,2-adduct that undergoes a novel sequence of a concerted Brook rearrange-ment/cyclopropanation and an anionic oxy-Cope rearrangement. 

Photochemical reactions can produce highly reactive intermediates for subsequent groimd state reactions. Photoisomerization of the cycloheptenone moiety in 151 led to a highly strained trans enol (152) that readily underwent a Diels-Alder reaction with isoprene to produce a mixture of 153 and 154, both of which were carried forward to a structure related to a naturally occurring tricyclic diterpene, vibsanin E (equation 12.94). Irradiation of the aldehyde... 

The zinc enolate formed as an intermediate in these conjugate addition reactions can be trapped by an electrophile in situ to provide further functionalization of the substrate. This is demonstrated by the synthesis of the anticancer agent clavularin B (eq 103). Sequential conjugate addition to cycloheptenone of Me2Zn in the presence of catalytic CuOTf-chiral peptide ligand complex, and enolate alkylation with 4-iodo-1-butene provide the key compound with 97% ee. 

In a further demonstration of the preparative potential of this chemistry, multigram quantities of four-membered carbocycles were investigated (Scheme 4.6) [24,26]. The reaction of 22.0 mmol of silyl enol ether with methyl acrylate gave the desired cyclobutane 2 a in 90% yield. Furthermore, multigram quantities of four-membered carbocycles were obtained from cycloheptenone in two steps, without purification of the intermediate silyl enol ether. These two-step sequences, using methyl acrylate and ethyl propiolate, led to large-scale production of the respective bicyclic cyclobutane 20d and cyclobutene 22c, in excellent overall yields. 

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