Protective groups for carbonyl compounds

Oximes have been used as protecting groups for carbonyl compounds owing to their hydrolytic stability. Consequently, the development of newer deoximation reagents... 

Dithioacetals are useful in organic synthesis as protective groups for carbonyl compounds, as precursors of acyl carbanion equivalents or as electrophiles under Lewis acidic conditions. The DBSA-catalysed system was also found to be applicable to dithioacetal-ization in water. In addition, easy work-up has been realized without the use of organic solvents when the products are solid and insoluble in water. In fact, the dithioacetaliza-tion of cinnamaldehyde on 10 mmol-scale with 1 mol% of DBSA proceeded smoothly to deposit crystals. The pure product was obtained in excellent yield after the crystals were filtered and washed with water (Equation (8)). This simple procedure is one of the advantages of the present reaction system. 

The enamine reaction provides an alternative method for selective alkylation and acylation of aldehydes and ketones. The enamine group is both a protecting group for carbonyl compounds and a directing or activating group for further elaboration. Note the relationship between enolates and enamines ... 

This reaction, like all acetalizations, is reversible. It is the basis for the wide application of dioxanes as protective groups for carbonyl compounds, as well as for systems with a 1,3-diol group, for instance the conversion of hexoses into so-called benzylidene derivatives [129] by the action of benzaldehyde in the presence of Lewis acids. The 6- and 4-OH groups are blocked simultaneously, forming a 1,3-dioxane ring, e.g. the a-methylglycoside 14 is converted into the dioxane derivative 15 ... 

Like all acetalizations, 1,3-dioxane formation is reversible it finds wide appHcation for establishing the 1,3-dioxane moiety as protective group for carbonyl compounds, as well as for systems with a 1,3-diol structural element. 

While our reaction was a solid-liquid-solid reaction, Hcylge s involved the use of concentrated aqueous sodium hydroxide and tetrabutyl ammonium hydroxide. It is noteworthy that the final polymer (IV) is much more effective in its use as a polymer-supported protecting group for carbonyl compounds (Ref. 29) than a somewhat similar polymer-bound diol prepared under standard conditions (Ref. 30, 31). 

Acetal formation is reversible (K for MeCHO/EtOH is 0-0125) but the position of equilibrium will be influenced by the relative proportions of R OH and H2O present. Preparative acetal formation is thus normally carried out in excess R OH with an anhydrous acid catalyst. The equilibrium may be shifted over to the right either by azeotropic distillation to remove H2O as it is formed, or by using excess acid catalyst (e.g. passing HCl gas continuously) to convert H2O into the non-nucleophilic H3O . Hydrolysis of an acetal back to the parent carbonyl compound may be effected readily with dilute acid. Acetals are, however, resistant to hydrolysis induced by bases—there is no proton that can be removed from an oxygen atom, cf. the base-induced hydrolysis of hydrates this results in acetals being very useful protecting groups for the C=0 function, which is itself very susceptible to the attack of bases (cf. p. 224). Such protection thus allows base-catalysed elimination of HBr from the acetal (27), followed by ready hydrolysis of the resultant unsatu-... 

Cyclic acetals are useful and common protecting groups for aldehydes and ketones, especially during the course of a total synthesis [8]. The successful synthesis of acetals frequently relies on the removal of water, a by-product of the reaction between the carbonyl compound and the corresponding diol. A Dean-Stark trap is often used for the removal of water as an azeotrope with benzene, but this method is not suitable for small-scale reactions. In addition, the highly carcinogenic nature of benzene makes it an undesirable solvent. Many of the reported catalysts for acetal synthesis such as p-toluenesulfonic acid and boron trifluoride etherate are toxic and corrosive. 

As already mentioned, 1,3-dioxepanes and their benzo-fused derivatives have often been synthesized as protecting groups for 1,4-diol units and acetals or ketones, respectively (cf. Section 13.11.6.6). They can be prepared in the usual manner by direct acetalization of the corresponding diol or carbonyl compound, as shown with the following example (Scheme 49) <2005HCA3151>. 

As previously mentioned, 1,4,2-dioxazoline rings may be used as a protected group for hydroxamic acids (see Section 6.04.6.3). In fact, this ring is susceptible to hydrogenolysis conditions (H2/Pd) affording carbonyl compounds <1996CHEC-II(4)525, 2002JOC4833>. 

Hemithioacetals may be transformed in two ways with Raney Ni. The sulfur group may be removed with the oxygen group intact as in eq. 13.78 or desurfiirized to recover the parent carbonyl compounds. In the ethylenehemithio acetal of a ketone, since the oxo group can be recovered by treatment with Raney Ni, this reaction makes it possible to use the hemithio acetal as a protective group for the carbonyl group (eq. 13.79). 

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