Desilylative condensations

Piperideines. Desilylative condense primary amine (CF3COOH promotion) result... 

The polymer showed significantly high thermal stability and was not decomposed even at 400°C (77). It was reported that poly(silylenephenylene)s can be S5m-thesized from the reaction of dichloromethylsilane or dicblorophenylsilane with p- and m-diUthiobenzene (78). An efficient method to prepare poly(silylene-m-phenylene) (12)(Afw = 4000-20,000), that is, a ruthenium-catalyzed desilylative condensation of m-bis(trihydrosilyl)benzene (eq. 12), was reported (79). 

In this section primarily reductions of aldehydes, ketones, and esters with sodium, lithium, and potassium in the presence of TCS 14 are discussed closely related reductions with metals such as Zn, Mg, Mn, Sm, Ti, etc., in the presence of TCS 14 are described in Section 13.2. Treatment of ethyl isobutyrate with sodium in the presence of TCS 14 in toluene affords the O-silylated Riihlmann-acyloin-condensation product 1915, which can be readily desilylated to the free acyloin 1916 [119]. Further reactions of methyl or ethyl 1,2- or 1,4-dicarboxylates are discussed elsewhere [120-122]. The same reaction with trimethylsilyl isobutyrate affords the C,0-silylated alcohol 1917, in 72% yield, which is desilylated to 1918 [123] (Scheme 12.34). Likewise, reduction of the diesters 1919 affords the cyclized O-silylated acyloin products 1920 in high yields, which give on saponification the acyloins 1921 [119]. Whereas electroreduction on a Mg-electrode in the presence of MesSiCl 14 converts esters such as ethyl cyclohexane-carboxylate via 1922 and subsequent saponification into acyloins such as 1923 [124], electroreduction of esters such as ethyl cyclohexylcarboxylate using a Mg-electrode without Me3SiCl 14 yields 1,2-ketones such as 1924 [125] (Scheme 12.34). 

The condensation of vinylallene 202 with ( )-crotonoyl cyanide gave the corresponding [4+2]-cydoadduct and the desilylated product in 35 and 25% yields, respectively. The regiochemistry was opposite to that of the reaction with ct/Tcnones, suggestive of a stepwise ionic mechanism [170],... 

The aldol condensation of benzaldehyde with the thioacetamide carbanion (RCHCSNRV), derived from the desilylation of the silyl-thioether with tetra-/i-buty-lammonium fluoride, is stereoselective at—80°C producing the erythro isomer of the p-hydroxy thioamide preferentially (Scheme 6.18, R = Me, erythro threo 95 5) via a conformationally mobile intermediate. However, when R is bulky, a greater amount of the threo isomer is formed. Predictably, as the reaction temperature is raised, so the stereoselectively decreases. This procedure contrasts with the corresponding condensation catalysed by titanium salts, where the complexed intermediate produces the threo isomer [47, 48],... 

Interest in the total synthesis of the Aspergillus terreus derived quadrone fi06), an antitumor agent has been very intense. Success was first realized in Danishefsky s laboratory Once 601 was reached, its sidechain was elaborated and ring closure effected (Scheme LII). Condensation of 602 with 1-tert-butoxy-l-tcrt-butyl-dimethylsiloxyethylene in the presence of titanium tetrachloride and subsequent desilylation resulted in introduction of an angular acetic acid moiety. The two sidechains were next connected by intramolecular alkylation and the resulting keto add was subjected to selenenylation in order to produce 603. The a, P-unsaturated double bond was used to force enolization to the a position. Indeed, 604 was... 

The yields are good and the selectivity is excellent. The chiral auxiliary is prepared from the corresponding ketone by Noyori s hydrogenation (both enantiomers are accessible) and can be removed, in high yield after SMS condensation, by a two-step sequence involving a desilylation-debenzylation. 

Hydrogenation of olefin 4, followed by 0-desilylation and 0-tosylation next procured tosylate 3, which cyclised readily when exposed to excess potassium hexamethyldisilazide. Elaboration of the ketophosphonate side chain of 20 was accomplished by condensing ester 2 with the lithiated anion of dimethyl methylphosphonate. After concurrent removal of the 1,3-dioxolane acetal and the MOM ether from 20, the resulting secondary alcohol was oxidised with pyridinium chlorochromate (PCC) to produce methyl ketone 1. 

Peterson olefination of the aldehyde 171b with l-trimethylsilylprop-3-ynyl lithium 137), furnished a (Z, E) mixture of enynes 225 in 85 % yield. Desilylation with KF in DMF l38), metalation with n-butyllithium, condensation with hexanal and lithium aluminum hydride reduction gave the conjugated dienol 226 in 72% overall yield from 171b. Treatment of 226 with 10 mol. % of PPTS 1011 in ethanol at 55 °C led directly, within 30 min, as monitored by t.l.c. to (E, E)-2-( 1,3-nonadienyl)-cyclo-butanone 227 (Eq. (70))96). This C3 -> C4 ring enlargement occurred under rather mildly acidic conditions since the pH of a 1 M aqueous solution of PPTS is 3.0 101 K... 

Aside from the ready preparation of some a,p-disubstituted cyclopentanones, the utility of the cyclopropanone hemiacetal approach has been illustrated by the total synthesis of the methyl ester of 11-deoxyprostaglandin E2 342 15). Towards this end, 1-trimethylsilylbutadiynylcyclopropanol 13, readily available from the cyclopropanone hemiacetal 3 (vide supra, Sect. 2.1, Eq. (6)) was successively treated with dihydro-pyran in CH2C12 in the presence of 10% mol. equiv. of PPTS 101). Desilylation by potassium fluoride in DMF 138), formation of the lithium salt with n-BuLi and condensation with hexanal gave the propargylic alcohol 339 in 64 % overall yield. The... 

When the acetal and the silyl enol ether are mixed with the same Lewis acid catalyst, Noyori found that an efficient aldol-style condensation takes place with the acetal providing the electrophile. The reaction is successful at low temperatures and only a catalytic amount of the Lewis acid is needed. Under these conditions, with no acid or base, few side-reactions occur. Notice that the final desilylation is carried out by the triflate anion to regenerate the Lewis acid Me3Si-OTf. Triflate would be a very poor nucleophile for saturated carbon but is reasonable for silicon because oxygen is the nucleophilic atom. 

In a different application, the reactivity of the condensing decarboxylase acetolactate synthetase was modeled (equation 7). C2a-hydroxyethylbenzothiazole was converted to its silyl ether, that on treatment with BuLi and methylpyruvate afforded the acetolactyl adduct, whose desilylation, followed by iV-alkylation, then treatment with Et3N in MeOH gave the methyl ester of acetolactate, along with some 2-acetylbenzothiazoline side product59. 

Cyclopropyl carbanions. Attempts to deprotonate cyclopropanes substituted by a electronegative group result in dimerization or trimerization. The desired carbanions can be generated in situ by desilylation of an a-(trimethylsilyl)cyclopropane derivative with BU4NF or C(,H,CH,N(CH,),F and used to effect aldol condensations. 

Reductive nucleophilic acylation. The reagent 1 condenses with aldehydes and ketones to give products (2) of carbonyl addition, which do not undergo syn-elimination of —OSi(CH3)3 in situ. However, treatment of 2 with KH in THF affords enol ethers (3) in excellent yields. The latter products are readily converted into aldehydes (4) on hydrol) is with 90% aqueous formic acid ( 90% yield, equation I). The adducts (2) are desilylated to 5 with CsF in DMSO (equation II). In this case, 1 functions as an equivalent of the —CH2OCH3 anion. 

Selective desilylatiou of bis(trimethylsilyi)acetylenes. The methyllithium-lithium bromide complex reacts with 1 or 2 to afford the corresponding monolithium derivatives in nearly quantitative yield. These readily condense with aldehydes and ketones to afford alcohols in 46-90% yield. Note that different solvents are used for 1 and 2. Selective desilylation of 1 or 2 can also be effected with 1-10 mole % KF-18-crown-6 in the presence of a carbonyl compound. In this case, the yields of product are usually somewhat lower. ... 

Cationic Pd complexes can be applied to the asymmetric aldol reaction. Shibasaki and coworkers reported that (/ )-BINAP PdCP, generated from a 1 1 mixture of (i )-BINAP PdCl2 and AgOTf in wet DMF, is an effective chiral catalyst for asymmetric aldol addition of silyl enol ethers to aldehydes [63]. For instance, treatment of trimethylsi-lyl enol ether of acetophenone 49 with benzaldehyde under the influence of 5 mol % of this catalyst affords the trimethylsilyl ether of aldol adduct 113 (87 % yield, 71 % ee) and desilylated product 114 (9 % yield, 73 % ee) as shown in Sch. 31. They later prepared chiral palladium diaquo complexes 115 and 116 from (7 )-BINAP PdCl2 and (i )-p-Tol-BINAP PdCl2, respectively, by reaction with 2 equiv. AgBF4 in wet acetone [64]. These complexes are tolerant of air and moisture, and afford similar reactivity and enantioselec-tivity in the aldol condensation of 49 and benzaldehyde. Sodeoka and coworkers have recently developed enantioselective Mannich-type reactions of silyl enol ethers with imi-nes catalyzed by binuclear -hydroxo palladium(II) complexes 117 and 118 derived from the diaquo complexes 115 and 116 [65]. These reactions are believed to proceed via a chiral palladium(fl) enolate. 

The conveniently prepared pyruvated benzyl glycosides 12candl2c (Table 2) are first converted by a two-step sequences into the fluoride 47 and the TlPS-deri-vative 48, respectively. The latter are subsequently condensed, using the glyco-desilylation-protocol, to give the desired laminaritjiosides 49 in excellent yield. 

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