Chemoselective protection

Smaller aldehydes form cyclic acetal-type oligomers readily in aqueous conditions.60 Diols and polyols also form cyclic acetals with various aldehydes readily in water, which has been applied in the extraction of polyhydroxy compounds from dilute aqueous solutions.61 E in water was found to be an efficient catalyst for chemoselective protection of aliphatic and aromatic aldehydes with HSCH2CH2OH to give 1,3-oxathiolane acetals under mild conditions (Eq. 5.7).62... 

If the introduction of the protecting group takes place through an irreversible reaction, then the chemoselective protection of one of two identical mutually interacting groups may be a critical step in the synthetic sequence. For instance, the monoprotection of 2,3-dihydroxynaphthalene (17) as the corresponding methyl... 

Chakraborti, A. K. Basak, A. Grover, V. Chemoselective protection of carboxylic acids as methyl esters a practical alternative to the diazomethane protocol. J. Org. Chem. 1999,... 

In addition to developing a facile route to the synthesis of thioacetals and thioketals, optimization of the reagents residence time within the packed bed enabled the authors to demonstrate the chemoselective protection of aldehydic functionalities in the presence of ketonic moieties (Scheme 34). 

Various carbonyl compounds were efficiently converted into the corresponding 1,3-dithiolanes using triethyl orthoformate as a water scavenger and (bromodimethyl)sulfonium bromide as an efficient catalyst under solvent-free conditions <2004EJ02002>. This protocol can be applied for the chemoselective protection of aldehydes in the presence of ketones on a large scale (Equation 73). 

In another variation, the chemoselectivity of the method was investigated. It is noteworthy that a few of the reported methods have demonstrated chemoselective thioacetalization of aldehydes in the presence of ketones. Therefore, this prompted us to explore the chemoselective protection of aldehydes in the presence of ketones. As can be seen in Scheme 3.15, when an equimolar mixture of methoxybenzalde-hyde and acetophenone was allowed to react with 1,2-ethanedithiol in the presence of a catalytic amount of TSA, benzaldehyde was exclusively protected, whereas acetophenone was intact under the same experimental conditions. 

Several efficient methodologies for chemoselective protection of specific amines on a variety of AG scaffolds have been reported in the literature. AG aminomethylene... 

To enable selective protection of amines other than the aminomethylene positions, other methods have been developed. The use of transition metal cations as a methodology for the chemoselective protection of amines on a variety of AGs has been developed and widely used [39-41]. The use of metal ions for the chemoselective N-carbamylation of the AG aparamycin (25, Scheme 6.3a) resulted in different products depending on the metal employed. When 4equiv of Ni(OAc)2 were used for the NH-carboxybenzylation reaction, the C-2 NH-Cbz product (26) was obtained as the single product in 82% yield. When a similar reaction was performed using Cu(OAc)2, the C-3 amine position of the 2-DOS was selectively N-carbamylated to yield the 3-NHCbz aparamycin derivative 27 in 87% yield. Finally, when the same reaction was catalyzed by Zn(OAc)2, a single product, which was carbamylated on the C-1 amine position (compound 28), was obtained in 31% yield. In the case of Zn(OAc)2, 5% of both the C-2 product 26 and the C-3 product 27 were obtained as well [42]. 

Reagent for the Protection of Secondary Amines. SEM-Cl has also maintained its prominence in the area of heterocyclic nitrogen protection. Of particular note is the use of SEM-Cl for the chemoselective protection of uracil and indazole derivatives (eqs 23 and 24, respectively). 

Flores MA, Bode JW (2010) Chemoselective protection of alpha-ketoacids by direct annulations with oximes. Org Lett 12 1924-1927... 

Sato et al. made use of ln(OTf)3 to catalyze the protection of aldehydes and ketones with 2-mercaptoethanol to good effects [260]. Similar to previous reports, strong preference for aldehydes over ketones were observed, making chemoselective protection possible (Figure 8.119). 

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