Acetals protection

Kelly applied this chemistry to the synthesis of cyclosexipyridine 66. This is an example of an intramolecular variation to this method. Masked enal 65 was prepared and treated with the standard reagents. The acidic medium liberated the aldehyde from its acetal protection. This in situ formation of the reactive species, similar to the above example, then undergoes cyclization to the expected pyridine derivative 66. 

The (/ (-enantiomer of 5-amino-2,2-dimethyl-4-phenyl-l,3-dioxane has also been successfully used for asymmetric Strecker syntheses4In addition, the acetal protecting moiety of the auxiliary has been modified. No significant change in the Strecker syntheses of a-mcthylamino nitriles has been reported for these alternative auxiliaries50. 

Stork first demonstrated the utility of protected cyanohydrins as acyl anion equivalents in 1971 [2]. The acetal-protected cyanohydrin 8 was transformed into the corresponding anion with LDA in THF/HMPA, which was then alkylated with a range of alkyl halides, including secondary bromides (Scheme 2). A mild acidic hydrolysis yielded a cyanohydrin, which provided the ketone after treatment with base. The Stork cyanohydrin alkylation and its variants have become important methods in natural product synthesis [3,4]. 

While the molecular masses of expanded [n]pericyclines 82,83,122 can easily be determined by GC-MS analysis, higher dehydrocyclooligomers fail to vaporize sufficiently [7]. Fast atom bombardment mass spectometry (FAB-MS) had to be applied for the characterization of the acetal-protected expanded pericyclinones 123-126 and 176 [39]. Attempts to determine the molecular masses of the... 

The carbonyl group can be deprotected by acid-catalyzed hydrolysis by the general mechanism for acetal hydrolysis (see Part A, Section 7.1). A number of Lewis acids have also been used to remove acetal protective groups. Hydrolysis is promoted by LiBF4 in acetonitrile.249 Bismuth triflate promotes hydrolysis of dimethoxy, diethoxy, and dioxolane acetals.250 The dimethyl and diethyl acetals are cleaved by 0.1-1.0 mol % of catalyst in aqueous THF at room temperature, whereas dioxolanes require reflux. Bismuth nitrate also catalyzes acetal hydrolysis.251... 

Difficulty removing acetate protecting group from amide 29... 

Acetals Removing the acetal protecting group is easily achieved by acid-catalyzed hydrolysis, although catalytic hydrogenolysis is better for acid-sensitive compounds. The oxygen connected to the... 

Benzyl acetal protecting groups were hydrogenolyzed over Pd/C,159 over 20% Pd(OH)2/C in AcOEt for 2 hours,160 and over 10% Pd/C in AcOEt in the presence of NaHC03 for 30 minutes.161... 

Zemplen O-deacetylation followed by cleavage of the acetal protecting groups with aqueous TFA afforded G(0) dendron 451, whose reducing end was reductively animated with bismethylamino trisaccharide 452 using cyanoborohydride in 1 1 MeOH-H20 to furnish the G(l) dendron 435 in 48% yield. 

Monosaccharide residues containing vicinal hydroxyl groups are oxidized by periodate, and are subsequently removed in the reduction-hydrolysis step. Therefore, the positions to which such monosaccharide residues are linked can be located by methylation analysis performed before, and after, Smith degradation. Alternatively,59 the oxidized and reduced sample is methylated, the ether hydrolyzed, and the product realkylated with CD3I or CH3CH2I. This kind of procedure can have advantages over that first described. For example, methylation before the hydrolysis step hinders the acetal protection of hydroxyl groups that can occur in acid hydrolysis.7... 

Marchand and co-workers ° synthesis of 5,5,9,9-tetranitropentacyclo[5.3.0.0 .0 °.0 ] decane (52) reqnired the dioxime of pentacyclo[5.3.0.0 .0 °.0 ]decane-5,9-dione (49) for the incorporation of the four nitro groups. Synthesis of the diketone precursor (48) was achieved in only five steps from cyclopentanone. Thus, acetal protection of cyclopentanone with ethylene glycol, followed by a-bromination, and dehydrobromination with sodium in methanol, yielded the reactive intermediate (45), which underwent a spontaneous Diels-Alder cycloaddition to give (46). Selective acetal deprotection of (46) was followed by a photo-initiated intramolecular cyclization and final acetal deprotection with aqueous mineral acid to give the diketone (48). Derivatization of the diketone (48) to the corresponding dioxime (49) was followed by conversion of the oxime groups to gem-dinitro functionality using standard literature procedures. 

Dave and co-workers have reported a successful synthesis of 2,2,4,4-tetranitroadamantane (117) which uses the mono-protected diketone (113) as a key intermediate. In this synthesis (113) is converted to the oxime (114) and then treated with ammonium nitrate and nitric acid in methylene chloride to yield the em-dinitro derivative (115). This nitration-oxidation step also removes the acetal-protecting group to leave the second ketone group free. Formation of the oxime (116) from ketone (115), followed by a similar nitration-oxidation with nitric acid and ammonium nitrate, yields 2,2,4,4-tetranitroadamantane (117). In this synthesis the protection strategy enables each carbonyl group to be treated separately and thus prevents the problem of internal nitroso dimer formation. 

Rhodium( I)-catalyzed hydroformylation of cyclic enol acetals 1 leads to acetal-protected syn-3,5-dihydroxyalkanals 2 with extraordinarily high levels (>50 1) of diastereoselectivity (Scheme 5.2) [2]. The diastereoselectivity cannot be ascribed to any obvious steric bias, and serves as a powerful demonstration that the hydroformylation reaction may be subject to exquisite stereoelectronic control. Indeed, while the addition of a pseudo-axial methyl group to the acetal carbon (as in acetonide 3) has a deleterious effect on the rate of the reaction, the sy -diastereomer 4 is still produced selectively, in what is surely a contra-steric hydroformylation reaction. 

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