Acetals cleavage, selective

This reagent combination in a method developed by Seebach for selective acetal cleavage is consistent with the presence of ester groups in the molecule.10 Use of a Lewis acid for activation always leads to transformation of the more highly substituted alcohol into a bcn/yl ether. 

Having established the chiral synthesis of levoglucosenone 1 and its functionalized analogues in both enantiomeric forms, we next investigated the exploitation of 26, the functionalized isolevoglucosenone, for the enantiocontrolled construction of natural products on the basis of its inherent convex-face selectivity and functionality, in particular, the alkoxymethyl handle for the acetal cleavage. 

The stereoselective reduction of the ketone function of 9 leads to a direct entry to selectively protected aldopentoses ( inversion strategy ) (Borysenko et al. 1989), which greatly expand the potential of this new protocol (Scheme 5). Following Evans protocol the tetramethylammo-nium triacetoxyborohydride-mediated reduction provides the yyn-diol 15 constituting a protected D-ribose (95%, >96% de). The anti-selective reduction to 17 was obtained after silyl protection of the free hydroxyl group of 9 to the OTBS-ether 16 using L-selectride. The aldopentose 18 was then accessible via chemoselective acetal cleavage followed by in situ cyclization (47% over two steps, >96% de). 

Increased hydrolytic stability of the ester function is readily attained by shielding the carbonyl group from nucleophilic attack. Thus, pivalates are slow to deprotect compared with acetates and the protracted reaction times required for cleavage of the pivalate may be incompatible with other protecting groups such as the TBS ethers. In such instances, the pivalate may be cleaved in good yield by reduction with diisobutylalaneJ576 604 In a synthesis of Laurencin, a secondary acetate was selectively cleaved in the presence of a primary pivalate with lithium hydroxide in aqueous methanol [Scheme 4.337).640 Subsequent deprotection of the pivalate in the presence of the TBS ether was then effected with diisobutylalane. 

Mitsunobu reaction as well as by mesylation and subsequent base treatment failed, the secondary alcohol was inverted by oxidation with pyridinium dichromate and successive reduction with sodium borohydride. The inverted alcohol 454 was protected as an acetate and the acetonide was removed by acid treatment to enable conformational flexibility. Persilylation of triol 455 was succeeded by acetate cleavage with guanidine. Alcohol 456 was deprotonated to assist lactonization. Mild and short treatment with aqueous hydrogen fluoride allowed selective cleavage of the secondary silyl ether. Dehydration of the alcohol 457 was achieved by Tshugaejf vesLCtion. The final steps toward corianin (21) were deprotection of the tertiary alcohols of 458 and epoxidation with peracid. This alternative corianin synthesis needed 34 steps in 0.13% overall yield. 

The exolendo selectivity of the 1,3-dipolar addition of nitrones was regulated by the titanium salt as shown in Eq. (156) [398,399]. Aza-Cope rearrangement of a sugar-derived substrate initiated by the acetal cleavage with TiCl4 proceeded diastereoselec-tively to give the open-chain product (Eq. 157) [400]. 

This new procedure is especially valuable in the synthesis of benzoxazinones bearing one or two methoxy substituents or a 6,7-methylenedioxy unit at the aromatic ring. A drawback of the former methyl acetal cleavage method (Fig. (7), [110]) consisted in an insufficient selectivity of the boron trichloride mediated 2-methoxy group... 

Fig. (14). Synthesis of the 2,4-dihydroxy-2//-l,4-benzoxazin-3(4//)-one skeleton based on selective MOM acetal cleavage...

Removal of the MEM ethers and selective reprotection of the allylic hydroxyl group as the acetate afforded 274. Mitsunobu inversion of the cyclopentanol and acetate cleavage then provided synthetic brefeldin A (161). 

The Npys group can be cleaved reductively with BU3P, H2O or mercaptoetha-nol. It has also been cleaved with 2-mercaptopyridine, 2-mercaptomethylimidazole, or 2-mercaptoacetic acid in methanol/acetic acid. Selective cleavage of the 0-Npys bond over the 5-Npys bond can be achieved with the aromatic thiols. This group... 

Biirgi and Dubler-Steudle carried out principal component analysis of selected internal coordinates for the acetal fragment in the eight axial tetrahydropyranyl acetals reported by Jones and Kirby. The first principal component accounts for ca. 75% of the total variance, and its eigenvector clearly describes incipient acetal cleavage [194]. A model of the transition-state structure was obtained by linear extrapolation... 

Selective oxidation. 5-Hydroperoxy 1,3-dienes, after protection as peroxy-acetals, undergo selective cleavage at the remote double bond. The hydroperoxides themselves are available from ene reaction of skipped dienes with singlet oxygen. 

Reductive acetal cleavage. The reagent is a combination of BHj SMCj-BFj OEtj. Acetals derived from 1,2- or 1,3-diols bearing a neighboring hydroxy group can be selectively cleaved at the acetal C-0 bond proximate to the hydroxy group. 

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