Cyclic acetal protecting groups

Compounds bearing ci.r-l,2-diols and cis- and rrans-l,3-diols can be protected as cyclic acetals and ke-tals or cyclic orthoesters. As has been shown for ethers, these blocking groups are stable to bases but are... 

In a 4,6-benzylidene group, the conformation about C5-C6 is constrained to tg, so that the positive end of the C6-06 dipole points towards the developing positive charge on 05. Protection by cyclic acetals which enforce this conformation is thus strongly deactivating. 

In principle, all that remained to do to reach erythronolide (2) was to deprotect the Ci3 hydroxyl group of 62, conduct the macrolactonization, remove the acetonides, and carry out an oxidation state adjustment at C9. Of course this was easier said than done. The macrolactonization turned out to be very difficult. The Woodward group degraded Erythromycin A (1) to 17 thiopy-ridyl ester substrates, only three of which underwent lactonization under the Corey-Nicolaou conditions. Two of these derivatives gave low yields, but 63 cyclized to 64 in good yield. This effort established that (1) the 5-configuration was essential at C9 and (2) the C3-C5 and C9-C11 diol units had to be protected as cyclic acetals. Based on this information, carbamate-acetal 65 was eventually prepared Ifom the natural product and found to cyclize to 66 in 70% yield. Thus, to complete a total synthesis, it was necessary to convert w-acetorude 62 to 65, and move 66 forward to erythromycin A (1). 

CH2=C(OBn)CH2F, PdCl2(COD), CH3CN, it, 24 h, 89-100% yield. Protic acids can also be used to introduce this group, but the yields are sometimes lower. A primary alcohol can be protected in the presence of a secondary alcohol. This reagent also does not give cyclic acetals of 1,3-diols with palladium catalysis. 

Cyclic carbonates and cyclic boronates have also found considerable use as protective groups. In contrast to most acetals and ketals the carbonates are cleaved with strong base and sterically unencumbered boronates are readily cleaved by water. 

Catechols can be protected as diethers or diesters by methods that have been described to protect phenols. However, formation of cyclic acetals and ketals (e.g., methylenedioxy, acetonide, cyclohexylidenedioxy, diphenylmethylenedioxy derivatives) or cyclic esters (e.g., borates or carbonates) selectively protects the two adjacent hydroxyl groups in the presence of isolated phenol groups. 

X0 to hydroxy compounds. Lower temperatures favor ketone formation and sterically hindered carbonyls, such as 2-thienyl t-butyl ketone, are not reduced. The sensitivity of desulfurization to steric factors is evident by the failure to desulfurize 2,5-di-i-butyl-3-acetylthiophene. The carbonyl groups of both aldehydes and ketones can be protected by acetal formation, as particularly cyclic acetals are stable during desulfurization in methanol at room temperature. " The free aldehydes give primary alcohols on desulfurization. Another method to obtain only keto compounds is to oxidize the mixtures of ketone and secondary alcohol with CrOs after the desulfurization. - Through the desulfurization of 5,5 -diacetyl-2,2, 5, 2"-terthienyl (228), 2,15-hexadecandione (229) has been obtained, which... 

It was decided to construct a D-ring acylating agent bearing a latent C-8 vinyl group. To this end, benzylation of the known 5-bromo-orr/to-vanillin (22),14 followed by protection of the aldehyde carbonyl in the form of a cyclic acetal (1,3-dioxane), affords com-... 

Protective Groups for Diols. Diols represent a special case in terms of applicable protecting groups. 1,2- and 1,3-diols easily form cyclic acetals with aldehydes and ketones, unless cyclization is precluded by molecular geometry. The isopropylidene derivatives (also called acetonides) formed by reaction with acetone are a common example. 

Dioxacycloalkanes are cyclic acetals that are used frequently as protective groups. Substituted derivatives have been synthesized to achieve easy removal. Simplest of all, the 4-phenyl-1,3-dioxolane has not been used commonly because cleavage needs electrolytic conditions. A mild hydrogenolysis method was developed in 1997 to make this protective group more popular (Scheme... 

Although many examples of this type of ring system are known in the literature, the vast majority of these are cyclic acetals, which have been used as protecting groups for diols. These have not been included in this chapter. Otherwise, the majority of the compounds which fall into this category are either natural products or derivatives of, or precursors to, the natural products. 

Further, a large number of examples with simple alkyl substituents [168, 171, 176-184], cyclic alkanes [185], aryl substituents [177, 186-192], olefmic substituents [78, 177, 193-196], deuterated compounds [172], thioether groups [171], ester groups [197], orthoesters [198, 199], acetals [168, 182, 200-204], silyl-protected alcohols [198, 205-211], aldehydes [212], different heterocycles [213-217], alkyl halides [218, 219] and aryl halides [192, 220-223] have been reported. A representative example is the reaction of 92, possessing a free hydroxyl group, an acetal and a propargylic ether, to 93 [224] (Scheme 1.40). 

Photosensitive protecting groups discussed here belong to three different classes cyclic acetals, thioacetals, and hydrazones. 

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