Acetonides diol protection

Cyclic diol protecting groups are not always conducive to a successful RCM. For example, when Banwell and McRae submitted acetonide-protected 1,3-diol 28 to the Grubbs first-generation catalyst, none of the desired macrocyle was produced, but cyclohexene 29 was obtained in 81% yield, probably because the acetonide protecting group facilitated interaction of the double bonds of the carboxylic acid portion of the molecule (Scheme 2.11) [24]. To circumvent this problem, substrate 30 was synthesized, where the diol was protected as two silyl ethers, and RCM of this compound led to the desired 18-membered lactone 31 in 70% yield under the same reaction conditions. 

Similarly, ketone ( )-376 obtained by dihydroxylation of 366, followed by diol protection as acetonide, desulfonylation with Na/Hg, and Swem oxidation has been resolved by the Alex-... 

Previous efforts by McMurry accomplished the same conversion by heating the vinyl ether, with the diol protected as the acetonide, at 220°C in a base-washed silylated sealed glass tube containing toluene and sublimed sodium t-pentoxide, but the yield was lower, 60% [23]. 

The C. 100-C. 101 diol group, protected as an acetonide, was stable to the Wit-tig reaction used to form the cis double bond at C.98-C.99, and to all the conditions used in the buildup of segment C.99-C. 115 to fully protected palytoxin carboxylic acid (Figure 1,1). 

Acetonide formation is the most commonly used protection for 1,2- and 1,3-diols. The acetonide has been used extensively in carbohydrate chemistiy to mask selectively the hydroxyls of the many different sugars. In preparing acetonides of triols, the 1,2-derivative is generally favored over the 1,3-derivative, but the extent to which the 1,2-acetonide is favored is dependent on stmcture. Note that the 1,2-selectivity for the ketal from 3-pentanone is better than that from acetone. ... 

A variety of cyclic ortho esters,including cyclic orthoformates, have been developed to protect czs-1,2-diols. Cyclic ortho esters are more readily cleaved by acidic hydrolysis (e.g., by a phosphate buffer, pH 4.5-7.5, or by 0.005-0.05 M HCl) than are acetonides. Careful hydrolysis or reduction can be used to prepare selectively monoprotected diol derivatives. 

Selective protection of 1,2- and m-l,3-diols can be achieved by formation of acetonides, acetals or orthoesters. Further selectivity is possible in special cases (e.g., acetonide formation). With 17a,20,21-triols, the 20,21-acetonide is obtained exclusively. 16a,17a,21-Trihydroxy-20-lcetopregnanes (20) react selectively with acetone to give 16,17-acetonides (21). 

Acetonides are the most suitable base-stable protecting group for 16,17-cis-diols. They can be readily prepared from 16,17-disecondary alcohols with either the a- or j5-configurations. ... 

Steroidal cis vicinal diols at the 1,2-, ° 2,3-, ° 5,6- or 11,12- " positions can be selectively protected as acetonides, prepared by reaction with acetone at room temperature or at higher temperatures in the presence of hydrochloric, perchloric or -toluenesulfonic acids. Cis nonvicinal-diols can be similarly protected. 

A benzylidene acetal is a commonly used protective group for 1,2- and 1,3-diols. In the case of a 1,2,3-triol, the 1,3-acetal is the preferred product, in contrast to the acetonide, which gives the 1,2-derivative. The benzylidene acetal has the advantage that it can be removed under neutral conditions by hydrogenolysis or by acid hydrolysis. Benzyl groups and isolated olefins have been hydrogenated in the presence of 1,3-benzylidene acetals. Benzylidene acetals of 1,2-diols are more susceptible to hydrogenolysis than are those of 1,3-diols. In fact, the former can be removed in the presence of the latter. A polymer-bound benzylidene acetal has also been prepared. ... 

Tetramethoxybutane, TMOF, MeOH, CSA, 54-91% yield, trans-Diols are protected in preference to c/5-diols, in contrast to acetonide formation, which prefers protection of cis-diols." ... 

The completion of the synthesis of key intermediate 2 requires only a straightforward sequence of functional group manipulations. In the presence of acetone, cupric sulfate, and camphorsulfonic acid (CSA), the lactol and secondary hydroxyl groups in 10 are simultaneously protected as an acetonide (see intermediate 9). The overall yield of 9 is 55 % from 13. Cleavage of the benzyl ether in 9 with lithium metal in liquid ammonia furnishes a diol (98% yield) which is subsequently converted to selenide 20 according to Grie-co s procedure22 (see Scheme 6a). Oxidation of the selenium atom... 

The C2-symmetric epoxide 23 (Scheme 7) reacts smoothly with carbon nucleophiles. For example, treatment of 23 with lithium dimethylcuprate proceeds with inversion of configuration, resulting in the formation of alcohol 28. An important consequence of the C2 symmetry of 23 is that the attack of the organometallic reagent upon either one of the two epoxide carbons produces the same product. After simultaneous hydrogenolysis of the two benzyl ethers in 28, protection of the 1,2-diol as an acetonide ring can be easily achieved by the use of 2,2-dimethoxypropane and camphor-sulfonic acid (CSA). It is necessary to briefly expose the crude product from the latter reaction to methanol and CSA so that the mixed acyclic ketal can be cleaved (see 29—>30). Oxidation of alcohol 30 with pyridinium chlorochromate (PCC) provides alde-... 

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