2-Silyl-1,3-dithianes

Smith et al. have developed a very elegant route to complex polyol structures by sequential dithiane-epoxide coupling reactions (Scheme 7) [16]. Following the work of Tietze [17], 2-silyl-1,3-dithianes 42 are deprotonated with /BuLi in ether and converted into the stable lithium alk-oxides 43 with enantiomerically pure epoxides. A fast 1,4-Brook rearrangement occurs only after the addition of 0.3 equivalents of hexamethyl-phosphoramide (HMPA) or 1,3-dimethylhexahy-dro-2-pyrimidone (DMPU) to the reaction mixture. A new lithiated dithiane 44 that can undergo... 

Scheme 8.31 Smith Ill s three- and multicomponent linchpin coupling of metalated silyl dithiane 109 with epoxides.

The multicomponent linchpin coupling of silyl dithianes with epoxides was very efficiently used to access both the AB and CD spiroketal fragments of spongistatin. 

A unique bis-silylation system, in which a bis(silyl)palladium intermediate is generated via recombination of two Si-Si bonds, has been developed.8,97 A bis(disilanyl)dithiane reacts with alkynes in the presence of a palladium/ isocyanide catalyst, giving five-membered ring bis-silylation products in high yield with elimination of hexamethyl-disilane (Scheme 14). The recombination, that is, bond metathesis, is so efficient that no product derived from direct insertion of acetylene into the Si-Si bonds of the bis(silyl)dithiane is formed at all. 

Tietze and coworkers found a symmetrical bisalkylation of a silyl dithiane with 2 equivalents of an epoxide involving 1,4-silyl migrations369. Smith and Boldi applied the method to the unsymmetrical bisalkylation of silyldithiane 233 (equation 150)368. 

The location of the silyl protecting group in the coupling product from the reaction between a silyl dithiane and two different chiral epoxides is controlled by the order of the addition of the epoxides. Subsequent cyclisation of the derived 1,3-diketones provides an efficient route to a variety of 2,6-disubstituted dihydropyran-4-ones 39 <07JOC4280>. 

The difference in reactivity between the a-stannyl sulfide 16A and the a-silyl sulfide 16B can be explained by comparing the two-center energies of their carbon-metal bonds. Semiempirical molecular orbital calculation revealed that the bond energies decrease in the order of 2-silyl, 2-germyl, and 2-stannyl-1,3-dithiane cation radicals. As the silyl dithiane was completely consumed by the oxidation under the... 

The Brook 1,4-rearrangement is useful in cyclopentanol synthesis. For example, Schaumann and co-workers demonstrated that lithiated or-silyl dithiane 112 was useful for construction of cyclopentanol 115. Addition to epoxytosylate 113 followed by 1,4-silyl migration provided lithiodithiane 114 for closure of the five-membered ring. ... 

Sn2 VersusSN2 Reactionof2-TMS-l,3-Dithiane With Vinyl Epoxides. In 2002 Smith et al. demonstrated that 2-lithio-2-TMS-1,3-dithiane reacts with vinyl epoxides in an Sn2 fashion exclusively, while other, larger silyl dithianes afford mixtures of Sn2 and Sn2 products. Particularly useful, the large 2-lithio-2-triisopropyl-1,3-dithiane provides solely the Sn2 product. Furthermore, it was found that trans epoxides furnish syn products and cis epoxides produced anti products, albeit in modest yields (eq 28). However, under the reaction conditions (THF, HMPA) the TMS group underwent a 1,4-Brook rearrangement to afford a 1 1 mixture of the anticipated homoaUyhc alcohol and the rearranged silyl ether. 

A short synthesis of (5 ,9 )-(—)-indolizidine 223AB (1806) by Smith and Kim used the silylated dithiane 1847 as a linchpin for the one-pot tandem alkylation with epoxide (- -)-1848 and the N-tosylaziridine (—)-1849 (Scheme 233). The first intermediate is presumably alkoxide 1850, which undergoes a 1,4-Brook rearrangement to 1851 before reaction with the aziridine. The bis-alkylated dithiane (—)-1852 was isolated in... 

The carbanions derived from thioacetals, however, are typical -synthons. Most frequently used are 1,3-dithianes and C -silylated thioethers (see p. 33f. D. Seebach, 1969, 1973 B.-T. Grobel, 1974,1977). In these derivatives the proton is removed by butyllithium in THF. 

Similarly, in another example, alkylation of 111 with diepoxide (—)-115 (1 equiv.) in the presence of HMPA (1.3 equiv.) furnished diol (+)-117. Protection of (+)-117 to form the acetonide, removal of the silyl protecting groups (TBAF), and hydrolysis of the dithiane with Hg(Cl04)2 provided the diketone (+)-118. Hydroxy-directed syn-reduction of both carbonyl groups with NaBI U in the presence of Et2BOMe, and triacetonide formation, followed by hydrogenolysis and monosilylation, afforded the desired Schreiber subtarget (+)-119, which was employed in the synthesis of (+)-mycoticins A and B (Scheme 8.31) [56b]. 

Methoxytrimethylsilane, 123 Methyl acetoacetate, 92 Methyl bromoacetate, 107 Methyl 11-hydroxyundecanoate, 58 Methyl lithium, 27,28 Methyl 10-undecenoate, 58 2-Methyl-l, 3-dithiane, 81 (fl/ ,5 )-Methyl-3-phenyldiniethyl-silyl-3-phenylpropionic acid, 53-4 2-Methyl-3-Phenylprop-2-cnal, 111 2-Methyl 2-lrimethylsilyl-1,3-dithiane, 81 2-Methyl-l-(trimcthylsilyloxy)cyclo-hex-l-ene, 100,109 2-Melhyl-l-lrimethylsilyloxy)cyclo-hcx-6-enc, 100 2-Methyl-2-trimethylsilyloxy-pentan-3-one, 132 2-Methylacetophenone, 42-3 2-Methylbutyraldehyde, 85 2-Methylcyclohexanone, 99,100 2-Methylcyclohexanone, 131 4-Methyldec-4-ene, 67-8 Methylenation, 63 2-Methylpropen-l-ol, 131 Methyltriphenylphosphonium bromide, 27 Michael addition, 85 Monohydridosilanes, 128 Monohydroalumination, 29... 

Further evidence for the above-mentioned mechanism of HOMO elevation by group 14 elements is provided by studies of thioethers. The decrease in oxidation potential of silyl ethers as compared to ethers is not realized in the case of a-silylthioethers whereas a-stannyl substituents in thioethers cause a considerable cathodic shift in oxidation potential. Moreover, the effect is geometry-dependent. Values for substituted cyclic dithianes 15 are summarized in Table 21. The difference between Si and Sn in this case is illustrative. The lone nonbonding pair in the 3p orbital of sulfur is much too low in energy compared to... 

Palladium-catalyzed bis-silylation of a,/ -unsaturated ketones using bis(disilanyl)dithiane affords seven-membered ring silyl enol ethers in high yields via 1,4-addition (Equation (48)).8,97 Application of this reaction to a,/ -unsaturated esters and nitriles gives five-membered ring 1,2-addition products in good yields (Equation (49)). 

Suda and coworkers described the anodic oxidation of 2-silyl-l,3-dithianes which have two sulfur atoms on the carbon adjacent to silicon [42], In this case, however, the C Si bond is not cleaved, but the C-S bonds are cleaved to give the corresponding acylsilanes (Scheme 12). Although the detailed mechanism has not been clarified as yet, the difference in the anode material seems to be responsible for the different pathway of the reaction. In fact, a platinum plate anode is used in this reaction, although a carbon anode is usually used for the oxidative cleavage of the C-Si bond. In the anodic oxidation of 2-silyl-l,3-dithianes the use of a carbon anode results in a significant decrease in the yield of acylsilanes. The effects of the nature of the solvent and the supporting electrolyte may also be important for the fate of the initially formed cation radical intermediate. Since various 2-alkyl-2-silyl-l,3-dithianes can be readily synthesized, this reaction provides a convenient route to acylsilanes. 

Secondary alkyl selenides are reduced by (TMS)3SiH, as expected in view of the affinity of silyl radicals for selenium-containing substrates (Table 4.3) [40]. Reaction (4.23) shows the phenylseleno group removal from the 2 position of nucleoside [50]. Similarly to 1,3-dithiolanes and 1,3-dithianes, five- and six-membered cyclic selenoacetals can be monoreduced to the corresponding selenides in the presence of (TMS)3SiH [51]. The silicon hydride preferentially approached from the less hindered equatorial position to give transicis ratios of 30/70 and 25/75 for the five-membered (Reaction 4.24) and six-membered cyclic selenoacetals, respectively. 

The enantioselective lithiation of anisolechromium tricarbonyl was used by Schmalz and Schellhaas in a route towards the natural product (+)-ptilocaulin . In situ hthi-ation and silylation of 410 with ent-h M gave ewf-411 in an optimized 91% ee (reaction carried ont at — 100°C over 10 min, see Scheme 169). A second, substrate-directed lithiation with BuLi alone, formation of the copper derivative and a quench with crotyl bromide gave 420. The planar chirality and reactivity of the chromium complex was then exploited in a nucleophilic addition of dithiane, which generated ptilocaulin precnrsor 421 (Scheme 172). The stereochemistry of componnd 421 has also been used to direct dearomatizing additions, yielding other classes of enones. ... 

Activation of 2-silyl-l,3-dithianes was effected by tetrabutylammonium triphenyldifluorosilicate <1996JOC6901> or CsF <1999TL2065>. Both, equatorial and even axial silyl groups were reacted with electrophiles with retention of the configuration at C-2 when CsF was used for activation (Scheme 64) <2002SL1447>. 

An unexpected reactivity in the functionalization of 2-acyl-l,3-dithianes has been reported by Mioskowski and co-workers. They found that 2-acyl-l,3-dithianes with no further heteroatom at the acyl side chain react with aldehydes to give 2-acyl-2-hydroxyalkyl-l,3-dithianes, whereas a silyl-protected hydroxy group in the side chain of the 2-acyl-l,3-dithiane led to formation of the aldol product at the opposite site of the carbonyl group. Acyl chlorides always react with 2-acyl-l,3-dithianes to give the enol esters (Scheme 81) <2003TL213>. 

Oxygen at the heterocyclic sulfur atom has been functionalized in two ways (1) by a TMSOTf-catalyzed Pummerer reaction in the presence of a silyl enol ether (Scheme 95) <1998TL9131> or (2) by reductive removal of the oxygen using Ac20/Zn/cat. 4-dimethylaminopyridine (DMAP) <1996SL885>. The formation of 1,3-dithiane from 1,3-dithiane 1-oxide proceeds efficiently in 95% yield (Equation 70). 

For the very first report of a C- to O-silyl rearrangement occurring after epoxide opening with 2-TMS-l,3-dithiane, see P. F. Jones, M. F. Lappert, A. C. Szary, Journal of the Chemical Society, Perkin Transactions l 1973, 2272... 

Chloro-l,3-dithiane (797) has been employed as a formyl cation equivalent . The morpholine enamines of a variety of aldehydes and ketones were shown to react with this dithiane to produce the a-(l,3-dithan-2-yl) aldehydes and ketones (798) in good yield (Scheme 186) (77TL2077). In direct analogy with this work, the reaction of enol silyl ethers with 2-ethoxy-l,3-dithiolane in the presence of zinc chloride has been reported to afford half-protected 1,3-dicarbonyl compounds (81TL3243). 

Double silylation is also observed in the reaction of a,/3-unsaturated ketones with a bis(disilanyl)dithiane, resulting in high yields of cyclic silyl enol ethers [Eq. (65)].58 The catalyst for this reaction is a cyclic bis(silyl)pal-ladium(II) bis(ferf-butyl isocyanide) complex. Analogous reactions of ester... 

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