Acetonide, cleavage

The AgNC>3-induced reaction of (3-lactam-tethered a-allenic alcohols 41 gave, with concomitant acetonide cleavage, the spirocyclic dihydrofurans 42 in quantitative yields (Scheme 13) [59]. 

The correct stereochemistry of the C-1 hydroxyl is introduced by reducing the carbonyl group of 527 with L-Selectride. Acylation of the alcohol with ( S)-a-methylbutyric anhydride, oxidation of the TBPS-protected primary alcohol to an aldehyde, and acetonide cleavage affords the penultimate lactol 528. Oxidation of this lactol with Fetizon s reagent (Ag2C03/Celite) gives ( + )-compactin (97) or ( + )-mevinolin (98). 

Compared with chiral nonracemic a-amino carbonyl compounds - which are not suitable substrates for MBH reaction, mainly due to their racemization under normal conditions after prolonged exposure times to catalyst or due to poor diastereoselectivity " a-keto lactams, enantiopure 3-oxo-azetidin-2-ones 168, readily react with various activated vinyl systems promoted by DABCO to afford the corresponding optically pure MBH adducts 169 without detectable epimerization (Scheme 1.69). " However, the Lewis acid-mediated reaction of electron-deficient alkynes with azetidine-2,3-diones 168 as an entry to p-halo MBH adduets was not very sueeessful the coupling product 170 was achieved with concomitant acetonide cleavage as a single ( )-isomer in low yield, in the presence of trimethylsilyl iodide under BF3 OEt2-induced catalysis (Scheme 1.69). 

MgBr2-Et20, Mc2S, CH2CI2, it, 75-96% yield. " The failure of this substrate to undergo cleavage with the typical conditions was attributed to the presence of the 1,3-diene. Acetonides and TBDMS ethers were found to be stable. 

Conversion of silyl ethers to acetonides without prior cleavage of the silyl ether is possible (acetone, AcOH, CUSO4, 81 % yield), but is dependent upon the conditions of the reaction. Compare the following examples ... 

Cleavage rates for 1,3-dioxanes are greater than for 1,3-dioxolanes/ but hydrolysis of a trans-fused dioxolane is faster than that of the dioxane. In substrates having more than one acetonide, the least hindered and more electron-rich acetonide can be hydrolyzed selectively." In a classic example, 1,2-5,6-diace-toneglucofuranose is hydrolyzed selectively at the 5,6-acetonide. 

Although acetonides are generally considered stable to reagents like BH3, on occasion they can undergo unexpected side reactions, such as the cleavage observed during a hydroboration. ... 

Compounds i, ii, and iii can be prepared by an acid-catalyzed reaction of a diol and the cycloalkanone in the presence of ethyl orthoformate and mesitylene-sulfonic acid. The relative ease of acid-catalyzed hydrolysis [0.53 M H2SO4, H2O, PrOH (65 35), 20°] for compounds i, iii, acetonide, and ii is C5 C7 > acetonide C (e.g., t.//s for 1,2-O-alkylidene-a-D-glucopyranoses of C5, C7, acetonide, and C derivatives are 8, 10, 20, and 124 h, respectively). The efficiency of cleavage seems to be dependent upon the electronic environment about the ketal. ... 

For in = 2, 3) H5IO5, ether, THF, 77-99% yield. This method also cleaves oxathioacetals, but did not affect the acid-sensitive acetonide or 1,3-diox-olane. Note that ethereal periodic acid has been used to cleave terminal acetonides with subsequent glycol cleavage. ... 

During attempted acetonide formation of an amino alcohol derivative, smooth tosyl cleavage was observed. The reaction is general for those cases having a carboxyl group, as in the following example, but fails for simple amino alcohol derivatives that lack this functionality. ... 

Intermediate 8, the projected electrophile in a coupling reaction with intermediate 7, could conceivably be derived from iodolactone 16. In the synthetic direction, cleavage of the acetonide protecting group in 16 with concomitant intramolecular etherification could result in the formation of the functionalized tetrahydrofuran ring of... 

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 next key step, the second dihydroxylation, was deferred until the lactone 82 had been formed from compound 80 (Scheme 20). This tactic would alleviate some of the steric hindrance around the C3-C4 double bond, and would create a cyclic molecule which was predicted to have a greater diastereofacial bias. The lactone can be made by first protecting the diol 80 as the acetonide 81 (88 % yield), followed by oxidative cleavage of the two PMB groups with DDQ (86% yield).43 Dihydroxylation of 82 with the standard Upjohn conditions17 furnishes, not unexpectedly, a quantitative yield of the triol 84 as a single diastereoisomer. The triol 84 is presumably fashioned from the initially formed triol 83 by a spontaneous translactonization (see Scheme 20), an event which proved to be a substantial piece of luck, as it simultaneously freed the C-8 hydroxyl from the lactone and protected the C-3 hydroxyl in the alcohol oxidation state. 

To avoid the retro-Diels-Alder reaction, 56 was dihydroxylated prior to the introduction of the bromine atom (57). Removal of the acetonide group followed by cleavage of the diol afforded a bis-hemiacetal. Selective reduction of the less-hindered hemiacetal group gave 58. The remaining hemiacetal was protected, and the ketone was converted to an enol triflate, thus concluding the synthesis of the electrophilic coupling component 51. 

Thus, acid cleavage of the protective groups MOM and acetonide in 4 provides compound 3 (fragment B) desulfuration and oxidation of the hydroxyl group give compound 2 (fragment A) (Scheme 7-4). 

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