Silacycles

Synthetic modifications and applications of silacycles 98JCS(P1)2209, 99JCS(P1)81. 

Leighton has combined this concept of strained silacycles [62-66] with the asymmetric allylation chemistry in a series of pubhcations [60, 67-70], Leighton s aUyhc silacyclopentane 29 [67] (Scheme 20) works equally for allylation of aromatic and ahphatic aldehydes in the absence of additional Lewis bases (promoter activator) or Lewis acids with high yield and enantioselectivity. The mechanism of... 

By extension and application of this method, which our group is using for the preparation of silacycles , polysilacage molecules have been synthesized by Shimizu and coworkers, using the polylithium compounds 170-172 as building blocks (Figure 21) . 

Column chromatography was performed on 150 g of silica gel (100-210 /vm, Kanto Chemical Co., Inc. or Silacycle, Inc.). The product was eluted with 300 mL of 10% ethyl acetate-hexane, 300 mL of 25% ethyl acetate-hexane, and 1.8 L of 40% ethyl acetate-hexane, and 300-mL fractions were collected. 

The cleavage of a Si—Si bond in silacyclic compounds by lithium metal is the most versatile method to prepare linear, a, -dilithiated oligosilanes. The first dilithio compound obtained by Gilman and coworkers in this way was Li(Ph2Si)4Li (equation 29)72. 

The exceptional reactivity is explained by the authors as due to the enhanced polarity of the Si=C double bond. For a discussion of the effects see the references in the tables. In some cases, and preferably when R = Cl, the initially formed cycloadducts like E-426 or 429 undergo ring enlargements to other silacycles like 427 or 430. Interestingly,... 

VII. STRAINED SILACYCLES A. Silacyclopropyne and Other C2H2Si Isomers... 

Highly reactive small-ring mono-silacycles and medium-ring oligosilacycles... 

The temporary silicon connection method introduced by Stork is a useful protocol for the preparation of silaoxacycles. The C-Si bond in the silaoxacycles is readily convened to C-OH with retention of stereochemistry by oxidative procedures. Utimoto and co-workers have developed a novel method for the synthesis of triols using the temporary silicon connection method [95BCSJ625], Treatment of the silacycle 184 with tin hydride furnished a mixture of silacycles, which were converted to the triacetate 187 without isolation. The endo isomer 185 was formed as the major compound. 

The acetylene-insertion reaction presumably occurs by the following mechanistic sequence (1) insertion of Pd(0) into the SCB, (2) regioselective yy -silylpalladation of the acetylenic compounds to provide seven-membered l-pallada-4-silacyclic intermediate, and (3) reductive elimination of Pd(0) to afford silacyclohexene. Alternatively, /3-hydride elimination would open the palladacycle, generating a vinylpalladium hydride species that would undergo reductive elimination to yield the ring-opened allylvinylsilane. Isotopic labeling studies provided evidence in support of this mechanistic hypothesis (Scheme 47). 

In the case of vinyl radical cyclizations of 49E , the intermediate silacycle could be oxidized under Tamao conditions to afford ketone 51 (2) [124], The consequence is an umpolung installation of an acetyl group, with the vinyl radical serving as an acyl anion equivalent, further expanding the synthetic potential of the Si-tethered radical additions. 

A variety of diols also react with secondary silanes to give the 1,3-dioxa-2-silacycles in excellent yields.141 This method is superior to the alcoholysis... 

Tandem intramolecular silylformylation-allylation reaction of diallylhydrosilyl ethers derived from homoallyl alcohols is convenient for rapid, stereoselective synthesis of 1,3,5-triols convertible to more oxygen-functionalized compounds (Scheme 12).142,142a,142b 143 [ he second uncatalyzed allylation step would be facilitated by the formation of a strained silacycle intermediate, which has enough Lewis acidity to activate the formyl group. A similar tandem reaction via alkyne silylformylation has been reported.144... 

Weyenberg and Nelson (7) reported that the strained silacycles, 1,1-di-methyl-1-silacyclobutane (1) and l,l,3,3-tetramethyl-l,3-disilacyclobu-tane (2) undergo ring opening polymerization in the presence of platinum on carbon or chloroplatinic acid [Eqs. (11) and (12)]. 

Treatment of the allylic alcohols with diphenyldichlorosilane and 2,6-lutidine afforded the bis-alkoxysilanes 195 in excellent yield. These silicon-tethered compounds were treated with Grubbs catalyst to induce RCM reaction, furnishing the seven-membered silacycles 196 in 87-95% yield (Equation 37) <1998JOC6768>. 

Enantioselective Friedel-Crafts alkylation of A -benzylpyrrole and 5-nitroindole with benzoylhydrazones 504 promoted by a simple strained silacycle reagent 505 gives 2- and 3-derivatives 506 and 507, respectively (Scheme 102) <2005JA2858>. Indole itself provides the corresponding product with significantly reduced enantioselectivity (ee 24%). 

A similar strategy faces difficulty in the case of addition products. The only products that could not be formed by dimerization of the corresponding silirane intermediates are the four-membered ring compounds (disilacyclobutanes in the reactions of alkenes and disilacyclo-butenes in the case of alkynes). But these four-membered ring compounds may well be formed by further insertion of difluorosilylene into intermediate three-membered silacycles, for example ... 

This scheme was also used for the synthesis of a venlafaxine analogue containing a four-membered silacycle instead of a six-membered ring but Si-C bond cleavage with silacyclobutane ring opening took place in the amination step (Scheme 4) (04OM4987). 

Successful sila-modification of several peptides leading to new protease inhibitors (03CODD526) stimulated the elaboration of synthetic methods for the preparation of silicon-containing amino acids. Among these compounds a-amino acids-containing silacycles were synthesized... 

Benzoxazole and triazole derivatives 67 and 73b showed the highest antiatherosclerotic activity among all the investigated silacyclic S-sub-stituted heterocycles in mice maintained on high-cholesterol diet. They protected against an increase in serum low-density lipoprotein level and... 

These silacyclic compounds had a weak influence on vasodilatation on the isolated perfused rabbit ear blood vessels even in at 50/igml dose. The highest relaxation effect (18% at 10/igml ) was found for imidazole 66 (02MBD307). 

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