Trimethylsilyl ether, cleavage synthesis

The simultaneous and selective protection of the two equatorial hydroxyl groups in methyl dihydroquinate [11L1, Scheme 3.111 j as the butane-2,3-diace-tal 111 2 was a key strategic feature in a synthesis of inhibitors of 3-dehydroqui-nate synthase.205 Later in the synthesis, deprotection of intermediate 111.4 required three steps (a) hydrolysis of the trimethylsilyl ether and the butane-2,3-diacetal with trifluoroacetic acid (b) cleavage of the isopropyl phosphonate with bromotrimethylsilane and (c) hydrolysis of the methyl ester with aqueous sodium hydroxide. Compound 111 1 has also been used in the synthesis of inhibitors 3-dehydroquinate dehydratase206 and influenza neuraminadase207-208 as well as shikimic add derivatives.209 210... 

Stereospeeific synthesis of IJ-dieues. Corey el al. have described a new synthesis of 1,3-dienes based on the highly stereospeeific cis addition of alkylcopper reagents to a,p-acctylenic carbonyl compounds (3, 108). Thus the reaction of methyl 4-trimethyl-siloxy-2-nonynoate (I ) in THF with divinylcopperlithium (1.25 cq.) at - 90° and then at — 78° affords the pure madduct (2) in > 90% yield. Treatment of (2) with melhanolic hydrochloric acid effects cleavage of the trimethylsilyl ether and lactonization to give (3). 

The synthetic problem is now reduced to cyclopentanone 16. This substance possesses two stereocenters, one of which is quaternary, and its constitution permits a productive retrosynthetic maneuver. Retrosynthetic disassembly of 16 by cleavage of the indicated bond furnishes compounds 17 and 18 as potential precursors. In the synthetic direction, a diastereoselective alkylation of the thermodynamic (more substituted) enolate derived from 18 with alkyl iodide 17 could afford intermediate 16. While trimethylsilyl enol ether 18 could arise through silylation of the enolate oxygen produced by a Michael addition of a divinyl cuprate reagent to 2-methylcyclopentenone (19), iodide 17 can be traced to the simple and readily available building blocks 7 and 20. The application of this basic plan to a synthesis of racemic estrone [( >1] is described below. 

An important stage in the synthesis has been reached. It was anticipated that cleavage of the trimethylsilyl enol ether in 18 using the procedure of Binkley and Heathcock18 would regiospecifically furnish the thermodynamic (more substituted) cyclopentanone enolate, a nucleophilic species that could then be alkylated with iodo-diyne 17. To secure what is to become the trans CD ring junction of the steroid nucleus, the diastereoisomer in which the vinyl and methyl substituents have a cis relationship must be formed. In the... 

A practical synthesis of 1,3-OX AZEPINES VIA PHOTOISOMERIZATION OF HETERO AROMATIC V-OXIDES is illustrated for 3,1-BENZOXAZEPINE. A hydroboration procedure for the synthesis of PERHYDRO-9b-BORAPHENALENE AND PERHYDRO-9b-PHEN-ALENOL illustrates beautifully the power of this methodology in the construction of polycyclic substances. The conversion of LIMONENE TO p-MENTH-8-EN-YL METHYL ETHER demonstrates a regio-and chemoselective method for the PHOTOPROTONATION OF CYCLOALKENES. An efficient method for the conversion of a ketone to an olefin involves REDUCTIVE CLEAVAGE OF VINYL PHOSPHATES. A mild method for the conversion of a ketone into the corresponding trimethylsiloxy enol ether using trimethylsilyl acetate is shownforthe synthesis of (Z)-3-TRIMETHYLSILOXY-2-PENTENE. 

---