Silyl ethers reaction with

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]. 

Pd-catalyzed Heck reactions are among the most effective methods for the formation of quaternary carbon centers. Considering the significance and the strategic difficulties associated with the synthesis of quaternaiy carbons, particularly in the optically enriched or pure form, it is not a surprise that the development of catalytic asymmetric Heck reactions has held center stage for the past few years. One of the leading labs in this area is that of Shibasaki, who in 1993 reported a concise total synthesis of eptazodne 23 (Scheme 4).141 Thus, treatment of silyl ether 18 with 10 mol% Pd(OAc>2 and 25 mol% (S)-19 leads to the formation of 20 in 90 % yield and 90% ee As illustrated in Scheme 4, once the quaternary carbon center is synthesized efficiently and selectively, the target molecule is accessed in a few steps. 

The aldol reactions of enol silyl ethers, (16), with unprotected aromatic aldehydes also give good yields of the adducts (isolated as the silyl ether) but with... 

Benzylic silyl ethers couple with allylsilanes in the presence of trityl tetrakis [3,5-bis(trifluoromethyl)phenyl]borate (TFPB) catalyst leading to carbon-carbon bond formation (equation 77). The corresponding Z11CI2-catalyzed reactions with an allyl silyl ether lead to a mixture of regioisomers145,146. 

As an extension of this highly enantioselective Michael addition of silyl nitronates with a, p-unsaturated aldehydes, the reactions with cyclic a,p-unsaturated ketones as a Michael acceptor were also tested (Scheme 9.15). Cyclohexenone and cyclohepte-none were employed as a useful Michael acceptor with various silyl nitronates in the presence of catalyst (R,R)-6c, and gave the corresponding enol silyl ethers 28 with excellent stereoselectivities [30]. 

Cyclopropanone equivalent. Unlike cyclopropanone, which is difficult to isolate, 1 is stable, easily obtained from 3-chloropropionic acid (Aldrich), and is a useful substitute for the ketone. Thus reaction of the silyl ether 2 with RMgBr provides adducts in which the OH group of 1 is replaced by R. The carbinol 1 is also a useful precursor to pyrroles, pyrrolines, and pyrrolizidines (equation I). 

Aldol coupling of enol silyl ethers and ketals (6, 599). The reaction of the silyl ether 1 with dimethyl or dibenzyl ketals of 2-, 3-, or 4-methylcyclohexanone results in at least 92% selectivity for equatorial attack (equation I). The degree of equatorial attack... 

In contrast with the common activity of oxo-rhenium compounds in oxidation catalysis (see above), the Re -dioxo-complex [Re02l(PPh3)2] catalyzes the reductive hydrosilylation of aldehydes and ketones to give silyl ethers (reaction... 

A case of simple diastereoselection is illustrated in the reaction of the silyl ether 1 with fluoride65. The tetrahydropyran roe-2 was obtained in 90% yield and a ratio of diastereomers of 5.2 1. Unfortunately, the relative configurations of the diastereomers were not determined. 

The transition metal-catalyzed allylation of carbon nucleophiles was a widely used method until Grieco and Pearson discovered LPDE-mediated allylic substitutions in 1992. Grieco investigated substitution reactions of cyclic allyl alcohols with silyl ketene acetals such as Si-1 by use of LPDE solution [95]. The concentration of LPDE seems to be important. For example, the use of 2.0 M LPDE resulted in formation of silyl ether 88 with 86 and 87 in the ratio 2 6.4 1. In contrast, 3.0 m LPDE afforded an excellent yield (90 %) of 86 and 87 (5.8 1), and the less hindered side of the allylic unit is alkylated regioselectively. It is of interest to note that this chemistry is also applicable to cyclopropyl carbinol 89 (Sch. 44). 

Hydrosilylation of aryl alkyl ketones with trimethylsilane, catalyzed by a [PtCl2 (/f)-BMPP ] complex, gave (R)-silyl ethers (91) with low enantiomeric excesses,but a combination of dimethylphe-nylsilane and a Rh /(S)-BMPP complex gave (R)-silyl ethers (92) in 44-56% ee.ii-Mn use of a [ Rh(COD)Cl 2]/(-)-DI0P complex and a-naphthylphenylsilane" is effective for the reaction of a-keto esters, giving (/ )-a-hydroxy esters (93)." - ... 

Aryl triflate 13 is obtained by reaction of silyl ether 12 with CsF, CS2CO3 and Comins reagent at room temperature. Under these reaction conditions the TIPS-ether is cleaved to provide the corresponding phenolate, which undergoes reaction with Comins reagent to give triflate 13 in a one-pot protocol. 

Trapping of the Beckmann intermediates with enol silyl ethers affords facile entry to a variety of en-amino ketones. This condensation takes place with retention of regiochemical integrity in both oxime sulfonates and enol silyl ethers. Reaction of 6-methyl-l-(trimethylsiloxy)-l-cyclohexene (41) or 1-methyl-2-(trimethylsiloxy)-l-cyclohexene (42) with cyclohexanone oxime mesylate furnishes (43) or (44), respectively, as the sole isolable products (equation 25). Another striking feature of the reaction is the high chemospecificity. The condensation of the enol silyl ether (45), derived from p-acetoxyaceto-phenone, occurs in a chemospecific fashion with cyclododecanone oxime mesylate, the acetoxy moiety remaining intact (equation 26). Oxime sulfonates of aromatic ketones and cyclopentanones are not employable since complex reaction mixtures are formed. 

The synthesis of the C1-C9 fragment 120 began with an auxiliary controlled aldol reaction of the chloroacetimide 121, where chlorine is present as a removable group to ensure high diastereoselectivity in what would otherwise have been a non-selective addition (Scheme 9-39). The Lewis acid-catalyzed, Mukaiyama aldol reaction of dienyl silyl ether 122 with / -chiral aldehyde 123 proceeded with 94%ds, giving the 3-anti product 124, as predicted by the opposed dipoles model [3]. Anti reduction of the aldol product and further manipulation then provided the C1-C9 fragment 120 of the bryostatins. 

An intCTesting carbocationic cascade reaction was utilized as a key step in the total synthesis of cyclopiazonic acid 182 <05CC3162>. In the event, treatment of silyl ether 180 with triflic acid led to tetracycle 181 which was subsequently converted into 182. 

Lithium enolates of carboxylic acids Enamines and silyl enol ethers Reactions with Other Electrophiles... 

Silanes normally reduce aldehydes or ketones under catalytic conditions to the silyl ethers. However, with certain catalysts such as nickel sulfide,Co2(CO)8, or (Ph3P)3RhCl, carbonyl compounds react with silanes to yield an equilibrium mixture of enol silyl ethers (Scheme 17). In a similar vein, the silyl-hydroformylation reaction of cycloalkenes with CO and silanes may be a practical way to prepare enol silyl ethers. An example is the preparation of compound (49). Catalytic 1,4-hydrosilation of a, -un-saturated ketones or aldehydes gives the corresponding enol silyl ethers. The reaction is similar to the reductive silylation referred to previously, but the reaction conditions are neutral and milder. The formation of the enol silyl ether (50) is outlined below. ... 

The hexasubstituted benzenoid compound (145) is synthesized in one step by the condensation of 2 mol of the dienol silyl ether (146) with 1 mol of methyl orthoacetate and TiCU. The reaction is believed to proceed through the intermediate (147). Compound (147) can be considered as a potential 1,3,5-trielectrophile. The more reactive sites in (147) are at C-5 and at C-3 respectively. Condensation of (147) with a second mole of (146) gives therefore regioselectively the aromatic compound (145). By this method, the plant growth substance sclerin (148) can easily be prepared. 

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