Alkyl Silyl Ethers Preparation

The main applications of oxidation with chromium trioxide are transformations of primary alcohols into aldehydes [184, 537, 538, 543, 570, 571, 572, 573] or, rarely, into carboxylic acids [184, 574], and of secondary alcohols into ketones [406, 536, 542, 543, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584]. Jones reagent is especially successful for such oxidations. It is prepared by diluting with water a solution of 267 g of chromium trioxide in a mixture of 230 mL of concentrated sulfuric acid and 400 mL of water to 1 L to form an 8 N CrOj solution [565, 572, 579, 581, 585, 556]. Other oxidations with chromic oxide include the cleavage of carbon-carbon bonds to give carbonyl compounds or carboxylic acids [482, 566, 567, 569, 580, 587, 555], the conversion of sulfides into sulfoxides [541] and sulfones [559], and the transformation of alkyl silyl ethers into ketones or carboxylic acids [590]. 

Silyl ethers serve as preeursors of nucleophiles and liberate a nucleophilic alkoxide by desilylation with a chloride anion generated from CCI4 under the reaction conditions described before[124]. Rapid intramolecular stereoselective reaction of an alcohol with a vinyloxirane has been observed in dichloro-methane when an alkoxide is generated by desilylation of the silyl ether 340 with TBAF. The cis- and tru/u-pyranopyran systems 341 and 342 can be prepared selectively from the trans- and c/.y-epoxides 340, respectively. The reaction is applicable to the preparation of 1,2-diol systems[209]. The method is useful for the enantioselective synthesis of the AB ring fragment of gambier-toxin[210]. Similarly, tributyltin alkoxides as nucleophiles are used for the preparation of allyl alkyl ethers[211]. 

A convenient method for the preparation of 2-alkenylbis(cyclopentadienyl)zirconium(IV) alkoxides and -trialkylsilyloxides is the reductive metalation of the appropriate alkyl or silyl ethers by means of in situ generated bis(cyclopentadienyl)zirconium(II) 124. 

The alkyl allenyl ethers whose chemistry has been discussed are readily prepared and are useful for the synthesis of diverse cyclopentenones, as racemates or in enan-tiomerically enriched form. It is worth noting that silyl allenyl ethers allow entry into a distinct mechanistic manifold [16]. Triisopropylsilyloxyallene 47 can be deprotonat-... 

The ketone 73 was reduced chemo- and diastereoselectively and protected to provide the silyl ether 74. The ester function was then deprotonated to the corresponding ester enolate (75) that was alkylated with methyl iodide exclusively from the Re face of the enolate to afford the bicycle 76 (Scheme 11). The substrate for the retro-aldol reaction (77) was prepared by a sequence that consists of seven functional and protecting group transformations. The retro-aldol reaction converted the bicyclic yS-hydroxy ketone 77 into the 1,3-diketone 69 via the alkoxide (78) in very good yield. 

The same strategy has been used by Williams (90JA808) in his synthesis of brevianamide B. The aldehyde (82), prepared enantioselectively from L-proline, was converted to the silyl ether. Acylation of this (BuLi, ClC02Me) gave the carbomethoxy derivative as a mixture of diastereo-mers, which was alkylated by gramine. As before, an enolate alkylation (Sn2 ) on an allyl chloride derived from the above gave the tricyclic compound, which could be transformed to brevianamide B (Scheme 24). 

Dehydrobromination.3 One approach to trialkylsiloxyalkynes involves de-hydrobromination of 1, prepared from tribromoethanol, with BuLi (2 equiv.) to form (Z)-2-bromovinyl silyl ethers 2, which can be converted by LDA followed by alkylation into siloxyalkynes (4). These products undergo cycloaddition with vinyl... 

N-Alkylation in the azine ring is demonstrated by the preparation of 2-substituted 6-(jS-D-ribofuranosyl)oxazolo[5,4-rf]pyrimidin-7(6/T)-ones (181). In this case the silyl ether variant of the Hilbert-Johnson method for the synthesis of pyrimidine nucleosides has been used the pyrimidinone (180) is converted into its silyl ether using HMDS and the ether reacted with 2,3,5-tri-O-acetyl-D-ribofuranosyl bromide under Hg(II) catalysis. Deacetylation using methanolic ammonia gives the nucleoside with a /3-anomeric configuration (74JMC1282). 

Aldehydes, ketones, and acetals react with allyltrimethylsilane in the presence of a catalytic amount of BiX3 (X = C1, Br, OTf) to give homoallyl alcohols or homoallyl alkyl ethers (Equation (52)).91-93 The BiX3-catalyzed allylation of aldehydes and sequential intramolecular etherification of the resulting homoallylic silyl ethers are involved in the stereoselective synthesis of polysubstituted tetrahydropyrans (Equation (53)).94,95 Similarly, these Lewis acids catalyze the cyanation of aldehydes and ketones with cyanotrimethylsilane. When a chiral bismuth(m) catalyst is used in the cyanation, cyanohydrines are obtained in up to 72% ee (Equation (54)). a-Aminonitriles are prepared directly from aldehydes, amines, and cyanotrimethysilane by the BiCl3-catalyzed Strecker-type reaction. 

Nitrosolysis of camphor ethyl acetal with ethanolic ethyl nitrite in sulphur dioxide yields the orthoester oxime (205) which is rapidly dehydrated by excess acetal to the orthoester nitrile which then reacts with sulphur dioxide to form the ester nitrile and diethyl sulphite.Further papers in this section include the full paper on ozonolysis of silyl ethers (Vol. 5, p. 33), another synthesis of camphor-enol trimethylsilyl ether (cf. Vol. 6, p. 41)/°° the conversion of camphor oxime with Grignard reagents into the corresponding imine with no aziridine formation/° the preparation of (206) by treating bornylene with trichloroacetyl isocyanate/ the oxidation of thiocam-phor to the 5-oxide and alkylation in the presence of thallium(i) ethoxide to a/S-unsaturated sulphoxides/ and the free-radical C-3 alkylation of camphor with alkenes. " ... 

Carbonyl compound alkylations. Allylic alcohols and homoallylic silyl ethers are prepared from alkynes and dienes, respectively. 

The studies of Ban and Wakamatsu culminated in the preparation of three natural compounds from a single synthetic route (Scheme 1.15). The enediol bis silyl ether 63 was converted to the dianion and immediately alkylated with l-iodo-3-butanol to give glycol 64 as a mixture of diastereomers in 87% yield. Diol fragmentation with lead tetraacetate afforded keto lactone 65 in quantitative yield. Formation of the dithioketal and subsequent Raney nickel desulfurization then gave 66 (81%). Macrocyclic lactone 66 is the simple natural product... 

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