Protection-deprotection sequences

Titanium tetrakis(diethylamide) selectively adds to aldehydes in the presence of ketones and to the least hindered ketone in compounds containing more than one ketone. The protection is in situ, which thus avoids the usual protection/deprotection sequence. Selective aldol and Grignard additions are readily performed employing this protection methodology. ... 

A recent development has been the synthesis of bioerodible poly-phosphazenes that bear glyceryl side groups (35). The synthesis of these polymers requires a protection-deprotection sequence to reduce the functionality of the glycerol and prevent crosslinking. 

A further added-value of the combined use of DMC and zeolites, is that deri-vatization (protection/deprotection) sequences may be avoided. In particular, in... 

An alternative method for dialkyl peroxide synthesis is the nucleophilic addition of an alkyl hydroperoxide to an alkene under acid catalysis reported by Davies and coworkers (Scheme 31, path B) ". A similar reaction is the nucleophilic addition of alkylhy-droperoxides to vinyl ethers under acid catalysis, producing perketals. Perketals can be deprotected under mild conditions (THF/water/acetic acid) and this hydroperoxide protection-deprotection sequence has been used by Dussault and Porter as a means for the resolution of racemic hydroperoxides (see also Section II.A.2) . In this respect more detailed studies were carried out with the perketals 75, which were prepared via reaction of alkyl hydroperoxides with vinyl ethers (Scheme 33). Weissermel and Lederer reported that in the presence of teri-butyl hypochlorite, a-chlorodialkyl peroxides can be formed in yields between 12% and 45% (Scheme 31, path C)". a-Alkoxydialkyl peroxides and diperoxyacetals were prepared by Rieche and coworkers via acid catalyzed reaction of one or two equivalents of alkyl hydroperoxides with acetals, ketals or aldehydes (Scheme 31, path D)" or by methylation of the corresponding a-alkoxy hydroperoxides with diazomethane (yields 11%, 27%)" . The diperoxyacetals 76 were isolated in yields ranging from 39 to 77%. 

The chiral bicyclic enones, levoglucosenone, isolevoglucosenone, and new functionalized L-arabinose enone possess excellent reactivity and functionality. Their properties mid application as convenient precursors in the synthesis of many attractive templates or intermediates of complex natural products are reviewed. These compounds are attracting increasing interest due to their structural rigidity and ability for stereoselective functionalization without protection, deprotection sequences necessary in many synthetic organic methodologies. 

The vast array of similar functionality often turns out to be a major problem to the synthetic chemist who needs to differentiate between them. This can result in long, tedious, protection-deprotection sequences.1,6 7 Although enzymes can be of help, there is still a significant way to go. As carbohydrates are components of many pharmaceutical compounds, many methods have been developed for their synthesis.89 This includes methodology that is amenable to use at scale, including the Sharpless epoxidation.10-14... 

Moore et al. 100 expanded the use of the complimentary protection-deprotection sequence, facilitated by the diethyltriazine and trimethylsilane groups, to construct phenylacetylene oligomers. Up to 16 arylalkyne units were successfully connected (overall yield 67 % 2251 amu). The method, demonstrating a high level of chain length control ,... 

The /-butyl ester is often prepared by acid-catalyzed addition of the carboxylic acid to isobutylene. The overall protection-deprotection sequence is outlined in the following equation. Note that the /-butyl group is removed in the last step without destroying the phosphorus ester or the amide or benzyl ester groups. 

Obvious shortcomings of the Reichstein procedure are the modest yield (50— 60% from L-sorbose is often mentioned) and the acetone protection-deprotection sequence. Overall, 1 ton of sodium sulfate is produced per ton of ASA (acetone is recycled). It should be noted, on the other hand, that the catalytic hydrogenation and microbial oxidation steps are in all respects highly efficient, even by today s standards [153] and impeccably green [154]. 

In the Barbier-Grignard reaction (Figure 12.12), the protection—deprotection sequence can be avoided and the products isolated by simple phase separation (rather than by distillation of an organic solvent). This modification involves the use of zinc instead of magnesium to form the organometallic intermediate (see Li and Chan, 1997). 

In view of the need to eliminate the bulky protective groups and to reduce the number of steps involved in the protection-deprotection sequence, we developed a novel protective group of cysteine derivatives [57, 58]. 

Starting with 3,5-dibenzoyl-2-deoxy-D-ribose, Marriott and Bantick developed an abbreviated synthesis of Corey s tosylate intermediate, 67 (Scheme 3.26). Their sequence is similar to that shown in Scheme 3.25, but by starting with the deoxy sugar there is of course no need to remove the oxygen function, nor was it necessary to acetylate the hydroxyl group as in 66, thus eliminating a protection/deprotection sequence. 

Starting material 13-1 for a corticoid that incorporates three additional methyl groups can in principle be obtained from 12-1 in several steps involving protection-deprotection sequences. The enolate at C21 from treatment of 13-1 with lithium diisopropylamide (LDA) is then alkylated with methyl iodide to afford an intermediate, 13-2, in which the side chain on ring D has been extended by one carbon (Scheme 7.13). 

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