Silyl deprotection

Using a series of PASSflow reactors, with typical dimensions of 5 mm (i.d.) x 10 cm (long), Kirschning et al. (Kirschning and Gas 2003 Kirschning et al., 2001, 2006) demonstrated the ability to combine a series of immobilized reagents in order to perform a sequence of reaction steps. In one example, the group demonstrated an oxidation, followed by a silyl deprotection and reductive amination steps to afford a derivatized steroid 147, as illustrated in Scheme 38, in excellent yield and purity. 

Asymmetric synthesis of a chroman. Solladie and Moine have effected an en-antiospecific synthesis of the chroman-2-carboxaldehyde 7, a key intermediate in the synthesis of a-tocopherol, from (R)-( +)-l. The phosphonate 2, derived from 1, undergoes a Wittig-Horner reaction with the dimethyl ketal of pyruvaldehyde to afford the optically active vinyl sulfoxide 3. Condensation of the aldehyde 4 with the lithio derivative of 3 affords, after silyl deprotection, the allylic alcohol 5 as the only diastereoisomer. This... 

Conversion of D to (+)-testudinariol A (149) is summarized in Figure 6.8. After reduction of D with DIBAL-H, the resulting aldehyde E was treated with dimethylaluminum chloride in dichloromethane to give the cyclized product F after TBS protection. Ketone G, prepared from F, was then treated with a chiral phosphonoacetate H in the presence of NaHMDS to give the desired (Z)-ester as the major product. Reduction of the (Z)-ester with DIBAL-H furnished I. Alcohol I was converted to bromide J and sulfone K, respectively. Alkylation of K with J afforded L. Its reductive desulfonization and silyl deprotection yielded (+)-testudinariol A (149) in 4.4% overall yield based on A (19 steps). The spectroscopic... 

Solid-phase-bound reagents have also been used for precipitating excess reagents so that they may be removed by simple filtration. As an example, a combination of a resin-bound calcium sulfonate and a sulfonic acid resin is able to remove excess TBAF from silyl deprotection reactions. This treatment precipitates the fluoride as CaF2 whereas the tetrabutylammonium remains bound to the sulfonic acid resin [139]. 

Asymmetric syrc-selective aldol reaction of four carbons enolates (with attached chiral auxiliary) 290 and acrolein equivalent 291 was the key step in the Pettus synthesis of KDO [153]. Condensation adduct 292 was converted into the hydroxy lactone 293, which in turn after silyl deprotection and diol side chain installation gave lactone 204. Final addition of a carboxylic acid to the lactone carbonyl group of 204 was done with a-ethoxy vinyllithium. Reductive ozonolysis of the surrogate provided the ethyl ester 138 (Scheme 62). 

Selective reduction of the 4-keto group of either 410 or 411 gives an intermediate alcohol which, upon silyl deprotection, cyclizes to the bicyclic system 412 by an Sn2 mechanism. The product is obtained as a mixture of epimers at the C-2 carbon, but these are readily separated by column chromatography. 

An efficient synthesis of the alkaloid strychnine makes good use of an intramolecular Heck reaction. Oxidative addition of palladium(O) into the alkenyl iodide 212 and cyclization onto the cyclohexene gave, after p-hydride elimination and silyl deprotection, isostrychnine 213 (1.214). isomerization of the new alkene to give the enone and cyclization of the alcohol onto the enone gives strychnine. 

In 2008, the group of Williams [15] reported the first total synthesis of ( )-2-0-methylneovibsanin H (33) (Scheme 14.6). The diterpene, isolated from the leaves of Viburnum awabuki [16], was prepared by employing an acid-catalyzed domino sequence. Thus, the key transformation was the conversion of advanced intermediate 28 to cyclohexene 32 upon treatment with an excess of sulfuric acid in anhydrous methanol. Acid-mediated silyl deprotection first revealed alcohol 29, which readily underwent an intramolecular oxa-Michael addition to yield tricyclic 30. It was postulated that solvolysis and nucleophilic addition of methanol to the intermediary allyl cation then furnished acid 31, which underwent Fischer esterification. The resultant highly functionalized cyclohexene 32 was isolated in 50% yield as a mixture of diastereomers at C2 (diastereomeric ratio (dr) = 85 15). The observed stereochemistry at the newly created stereocenters, i.e., at C2 and C5, was postulated to arise from the preexisting sterically congested stereocenters in the starting material (i.e., 28). Cyclohexene 32 was eventually taken on to provide the natural... 

On the other hand, compound 245 was submitted to m-CPBA oxidation and the resulting N-oxide intermediate underwent a Cope reaction in acidic conditions to give N-hydroxypyrrolidine 246 in 77% yield (Scheme 41). The final steps of the synthesis were devoted to the construction of the intramolecular nitrone connection. For this purpose, appHcation of the Mukaiyama conditions generated in a regioselective fashion the nitrone intermediate, which collapsed via an intramolecular 1,3-dipolar cycloaddition to the required strained adduct. Final silyl deprotection furnished virosaine A (38) in 81% yield. 

Cossy et al. have reported a simple and general one-step protocol for the synthesis of various 5-amino-5-lactones from pyrrolidinones through the opening of a lactam ring [50] (Scheme 13). The fluoride-induced silyl deprotection of pyrrolidinones 66, followed by opening of the lactam ring via transacylation, paved the way for the synthesis of a variety of 5-amino-5-lactone 67 in one pot. 

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