Allylic TBS ether

The following examples illustrate how the local steric electronic environment can reverse the expected selectivity for the deprotection of TIPS ether verses a TBS ether. The allylic TBS ether is also less nucleophilic relative to the TIPS ether because of electron withdrawing character of the olefin. ... 

Most Lewis acids such as zinc bromid in methanol, dichtoroethylalane in di-chloromethane, trifluoroborane etherate and ethane-1,2-dithiol in methanol, or iron(III) chloride will also cleave trityl ethers. Scheme 4.202 illustrates the use of zinc bromide in dichloromethane to remove a trityl ether in the presence of two allylic TBS ethers during a synthesis of ACRL toxin Illb. ... 

The sulfone moiety was reductively removed and the TBS ether was cleaved chemoselectively in the presence of a TPS ether to afford a primary alcohol (Scheme 13). The alcohol was transformed into the corresponding bromide that served as alkylating agent for the deprotonated ethyl 2-(di-ethylphosphono)propionate. Bromination and phosphonate alkylation were performed in a one-pot procedure [33]. The TPS protecting group was removed and the alcohol was then oxidized to afford the aldehyde 68 [42]. An intramolecular HWE reaction under Masamune-Roush conditions provided a macrocycle as a mixture of double bond isomers [43]. The ElZ isomers were separated after the reduction of the a, -unsaturated ester to the allylic alcohol 84. Deprotection of the tertiary alcohol and protection of the prima-... 

Interestingly, MCPBA epoxidation of cis alcohol 16 affords a mixture of diastereomeric epoxides (55 45 mixture). Furthermore, protection of the allylic alcohol as TBS ether (17) and subsequent epoxidation results as well in hardly any stereochemical selectivity (53 47 mixture). With regard to these results it is suggested that the trans-allylic hydroxy group is effectively involved in directing the MCPBA epoxidation event. 

Scheme 16.11 shows the completion of the total synthesis of azaspiracid-1, which followed with slight modifications, the synthesis of the originally proposed structure of azaspiracid-1 (la). This chemistry was also carried out with the corresponding ABCD enantiomer in similar yields. Thns, lithiation of dithiane 51 (n-BuLi n-BnjMg) followed by addition into pentafluorophenol ester 68 resulted in CJ-C27 ketone 69 (50% yield). Ketone 69 was then elaborated into diacetate 70, this time as the TBS ether at C-25, as this protecting group was easier to remove than the acetate used in the earlier work directed toward the original stractnre (see Scheme 16.8). Stille coupling of this allylic acetate (70) then proceeded smoothly, as before, affording the complete Cj-C q backbone 71, which was successfully elaborated to the correct structure of azaspiracid-1 (1), identical in all measured physical properties ( H NMR, C NMR, Rf, [aj ) to the natural material.

Maiti and Roy reported a selective method for deprotection of primary allylic, benzylic, homoallylic and aryl TBS ethers using aqueous DMSO at 90° C. All other TBS-protected groups, benzyl ethers, THP ethers as well as methyl ethers remain unaffected. 

First, the allylic alcohol is protected as the TBS ether. Then, the methyl ester is hydrolyzed. 

A number of investigations have explored the reactions of ally lie stannanes containing a y-alkoxy substituent. A direct preparation of these substances utilizes the kinetic deprotonation of an allyl ether followed by alkylation with tri-n-butylstannyl chloride. In a typical experiment, the deprotonation of 101 with 5-butyllithium leads to internal coordination of lithium cation and provides formation of the Z-allylstannane 102. The behavior of y-alkoxyallylstannanes is similar to the corresponding Z-alkylstannanes, and as a result, the reaction provides a stereoselective route for the synthesis of complex diol derivatives. In the allylation of chiral aldehyde 80 with stannane 102, /l-chelation dictates face selectivity. The expected. yyn, anti-product 104 is obtained with high diastereoselection via the antiperi-planar 103, which accommodates the sterically demanding silyl (TBS) ether (Scheme 5.2.23).23... 

I2, CH2CI2, 3A ms, 1-8 h, rt, 22-94% yield. The Bn, allyl, and TBDMS ethers are stable to these conditions, but TBS ether is partially cleaved. Phenolic prenyl ethers react to give chromanes. 

Peracids m-CPBA and CF3CO3H have been used in epoxidations of substrates with two mnable allylic directing groups expected to direct the peracids to opposite faces of the alkene. Control of face selectivity was observed and attributed to the different binding abilities of the two peracids to the various allylic functionalities, carbamate on one side of the alkene and alcohol, methyl ester, acetate, trifluoroacetate, or TBS-ether on the other. The conversion of A-mono-protected and A-di-protected cyclopent-... 

The presence of the bidentate chelate in allylation reactions was supported by C NMR studies with the anti halide and phenylselenide substrates in the presence of MgBr2-OEt2 [5]. The introduction of a bulky protecting group such as tert-butyldimethylsilyl ether (TBS) on the hydroxyl function led to the syn allylated product (Scheme 2) [4] and was thus shown to prevent chelation of the bidentate Lewis acid in favor of monodentate complex formation. C NMR studies with TBS ether in the presence of MgBr2 OEt2 validated this finding [5]. 

Since the C13-C14 olefin does not alter the reactivity of the C1-C9 portion of the myriaporone intermediates, subsequent efforts were explored on the C13-PMB ether (Scheme 12). Substrate 26 was successfully reduced with Raney nickel, and the trimethylsilyl ether was selectively cleaved with TBAF at -35 C. The C5 alcohol was selectively protected as the corresponding TBS ether, and C7 allylic alcohol was then oxidized under Dess-Martin conditions to provide bis-silyl ether 31. 

Allylic ethers also undergo catalytic ethylmag-nesation with excellent selectivity and in good yield (Table 4.2). However, there are several notable differences between the reactions of allylic ethers and alcohols (I) Zr-catalyzed reactions of allylic ethers afford the anti diastereomers predominantly (vs. the syn isomers observed for alcohols). (2) As the size of the or-alkyl substituent increases, reaction selectivity is also increased, which is also in contrast to the reactions of allylic alcohols. Needless to say, the complementary levels of selectivity observed in reactions of allylic alcohols and ethers represents a useful attribute for applications in organic synthesis. Finally, it is also worth noting that with sterically bulky oxygen substituents, reaction efficiency can suffer significantly allylic silyl ethers (TBS (terl-butyldimethylsilyl)) afford <5% products under identical conditions. 

Allyl alkyl ethers are converted to ketones on reaction with /-BuOOH in the presence of a catalytic amount of CrO, in dichloromethane at room temperature. This oxidation does not affect THP, TBS, and MOM ethers. 

Removal of protecting groups. A combination of DBU with a thiol can be used in the removal of an Fmoc group in a large scale process. Regeneration of alcohols from trichloroacetimidates is accomplished by treatment with DBU in MeOH (other methods involve acid-catalyzed hydrolysis and Zn dust reduction)." Alcohols temporarily protected as trichloroacetimidates permit their differentiation from others that are masked in acetonide, ester (acetate, benzoate, etc.), and ether (allyl, TBS, etc.) forms. 

---