5-Trimethylsilyl-3-cyclohexenone

Trimethylsilyl)vinylketen (20), prepared in four steps from l-(trimethyl-silyl)propyne in 40—60% yield, participates in Diels-Alder reactions as a reactive diene, generating a-(trimethylsilyl)cyclohexenones directly from olefinic dienophiles (Scheme 18). °... 

A comparison of the configuration of the substrates and reaction products shows that the oxiranyl anions arc configurationally stable under the reaction conditions. Only one example is known in which isomerization was observed. When the ci.v-tm-butyl-substituted epoxysilane27 was metalated and quenched with 2-cyclohexenone, addition product 27 was obtained under inversion of the anionic center. Presumably the strain created in forcing the ter/-butyl and the trimethylsilyl group cis on the oxirane ring facilitates the isomerization process13. 

A resident stereocenter in the enone part can control the formation of two new stereocenters in one step, guided by a synclinal transition state and an axial cyclization mode. The major product on cyclization of 4-methyl-3-[6-(trimethylsilyl)-4-(Z)-hexenyl]-2-cyclohexenone was formed in a ratio of 7.5 13S. 

To a solution of 6.99 g (25.3 mmol) of 2,3,4-trimethyl-4-(5-trimethylsilyl-3-pentynyl)-2-cyclohexenone in 150 mL of C HjClj are added at —78 C 5.1 mL (44 mmol) of TiCl4, and the resultant mixture is stirred for 30 min at —78 "C. The mixture is quenched at low temperature with 100 mL of water and extracted with three 50-mL portions of Ch,C12. The combined organic phase is washed with 150 ml, of brine and dried over MgS04. The solvent is removed in vacuo and the crude product is flash chromatographed (EtOAc/ petroleum ether 3 97) to give the pure product as a 2 1 mixture of diastcreomers yield 4.32 g (84%) d.r. 2 1. 

Dienones, such as 4-[4-(trimethylsilyl)-2-butenyl]-3-vinyl-2-cyclohexenone, are useful precursors for these particular transformations the allylsilane side chain is too short for effective 1,4-addition, but just right for 1,6-addition, resulting in six-ring annulation. Three different Lewis acids can be used titanium(IV) chloride, boron trifluoride diethyl ether complex, and ethylaluminum dichloride. The best chemical yields and complete asymmetric inductions were obtained with ethylaluminum dichloride. 

Using 3-substituted cyclohexanones the /rans-diastereoselective synthesis of decalones and octahydro-1 //-indenones may be achieved 164 169. This method has been applied, for instance, in the synthesis of 19-norsteroids. In a related Michael addition the lithium enolate of (R)-5-trimethylsilyl-2-cyclohexenone reacts with methyl 2-propenoate selectively tram to the trimethylsilyl substituent. Subsequent intramolecular ring closure provides a single enantiomer of the bicyclo[2.2.2]octane170 (see also Section 1.5.2.4.4.). 

For example, using (/ )-5-trimethylsilyl-2-cyclohexenone as the chiral Michael acceptor, optically active m // .v-3.5-disubstituied cyclohexanones 1 are obtained via a Lewis acid catalyzed addition of silylenol ethers or ketene acetals. 

Danishefsky s diene).46 The two donor substituents provide strong regiochemical control. The D-A adducts are trimethylsilyl enol ethers that can be readily hydrolyzed to ketones. The (3-methoxy group is often eliminated during hydrolysis, resulting in formation of cyclohexenones. 

Macdonald and Dolan have reported a new route to the tropinone system (88). 2-Cyclohexenone (160) is transformed to 2-[(trimethylsilyl)oxyl]-l,3-cyclohexadiene (161), and then by dichlorocyclopropanation to 162 and by acid-catalyzed hydrolysis to 2-chloro-2,6-cycloheptadienone (163). Addition... 

A seven-membered ring is formed in the cyclization of 195 (equation 95)105. The homologue 196 affords the fused cyclooctane 197, together with the cis- and trans-decalinones 198 (equation 96)106. Six-, seven- and eight-membered rings are produced in Lewis acid-catalysed reactions of various cyclohexenones with side-chains terminating in allylic trimethylsilyl groups (equations 97 - 99)107. 

The silylcuprate conjugate addition reaction has been used for the protection of an enone double bond, which can be regenerated with CuBr2 [22a], and for the strategic introduction of the silyl substituent for stereocontrol and regiocontrol purposes. Enantiopure 5-trimethylsilyl-2-cyclohexenone can be prepared by conjugate addition reaction [44] and the appropriate enantiomer has been converted into a number of natural products (Scheme 3.4) [38]. These synthetic strategies exploit... 

Scheme 3.4. Synthesis of enantiopure (-t)- and (-)-5-trimethylsilyl- and 5-tri-n-butylstannyl-2-cyclohexenone [44] and natural products prepared from the silyl synthons [38].

Scheme 6.6. Diastereoselectivity in conjugate additions of organocuprates to chiral bicyclic cyclohexenones (TMS = trimethylsilyl).

The copper-catalyzed conjugate addition of methyhnagnesium iodide to cyclohexenone and trapping of the resulting enolate as its trimethylsilyl enolate, followed by TrSbCle-catalyzed Mukaiyama reaction, are the first steps of an elegant synthesis of enantiomeri-caUy pure clerodanes (equation 45). 

The copper-catalyzed conjugate addition of methyl magnesium iodide to cyclohexenone and trapping the enolate as its trimethylsilyl enol ether, followed by a trityl hexachloro-antinomate-catalyzed Mukaiyama reaction, is apphed to / -(—jcarvone. C-2, C-3 functionalized chiral cyclohexanones are converted into their a-cyano ketones, which are submitted to Robinson annulation with methyl vinyl ketone. Highly functionalized chiral decalones are obtained that can be used as starting compounds in the total synthesis of enantiomerically pure clerodanes (equation 70). 

Allenylsilanes react with a,p-unsaturated acylsilanes to give trimethylsilyl-sub-stituted cyclopentenes (equation I) the reaction of allenylsilanes with a-methyl-a,p-unsaturated acylsilanes results in silyl-substituted cyclohexenones.2... 

Conditions of the reaction govern its result and solvent plays an important role. As an example, irradiation of cyclohexenones in the presence of trimethylsilyl-methyldiethylamine leads to a mixture of silylated and non-silylated aminocyclo-hexanes with a ratio that depends on the solvent used acetonitrile yields silylated compounds as the major products, whereas they are the minor products in methanol.285 286... 

It has already been explained that irradiation of a tertiary SMA can produce an a-amino radical by rupture of a C-H or the C-Si bond. The former case allows the transformation of an MSMA into an RSMA (see Section IV.C.7). Here are disclosed the results of the irradiation of tertiary SMAs under conditions in which cleavage of the C-Si bond occurs to yield a non-silylated adduct. Thus, the reaction of /V-(trimethylsilyl-methyl)diethylamine with various cyclohexenones leads to a mixture of the silylated and non-silylated (3-adducts, depending upon the solvent used (see Section IV.C.7). In methanol, protodesilylation predominated.285,286... 

Cyclopentanones.4 The adducts 2, obtained by reaction of trimethylstannyl-lithium with cyclohexenone followed by trapping with an electrophile, when treated with a Lewis acid can give rise to cyclohexanones and/or cyclopentanones. TiCl4 tends to give mixtures of both products, whereas trimethylsilyl triflate favors formation of cyclopentanones. Thus the adduct 5 on treatment with TMSOTf provides only the cyclopentanone 6. Reaction of 5 with TiCl4 gives 6 and 7 in the ratio... 

In addition to the simple and reagent-induced diastereoselectivity observed in the reaction of thiols with unsaturated compounds, an interesting kinetic resolution takes place when racemic 5-trimethylsilyl-2-cyclohexenone is treated with 0.55 equivalents of 4-methylbenzenethiol in the presence of cinchonidine12. The reaction results in the formation of the tram-adduct tram-14 as the major product together with small amounts of the m-addition product cis-14 and unreacted starting cyclohexenone that is partially resolved. 

A definite improvement in the synthesis of A -methoxy aziridines was achieved by substituting boron trifluoride with trimethylsilyl triflate and diethyl ether with dichloromethane"9. In this way, the A -methoxy aziridines were obtained in good yields from a variety of linear and cyclic alkenes, e.g., 6-8. For comparison, the aziridine 8 was obtained in 50% yield by using boron trifluoride- diethyl ether complex in dichloromethane. Complex product mixtures were obtained with allyl and crotyl alcohols and with cyclohexenone. Further transformation of the A -methoxy aziridines into the N-H aziridines was possible using sodium/ ammonia reduction, e.g., 9. 

Trimethyisilyllithium reacts with 2-cyclohexenone to give the enolate anion which on methylation affords exclusively traH.s-2-mcthyl-3-(trimethylsilyl)cyclohexanone (trans-1) in 97% yield17. 

Mariano and coworkers have shown that photoreactions of silylated tertiary amines such as 242, with a cyclohexenone derivative 241 give two types of adduct, the trimethylsilyl (TMS) containing adduct 243 and the non-TMS adduct 244 (Scheme 58) [303-305]. 

Both cyclic and acyclic enone systems participate in the (trimethylsilyl)cyclopentene annelation (Table 6). a-Methylene ketones react to form spiro-fiised systems and the intermediates derived from ace-tylcyclohexanone, cyclohexenone and cyclopentanone cyclize to yield S,S- and 6,3-fiised ring systems. ... 

---