Acetonide protected

In all cases examined the ( )-isomers of the allylic alcohols reacted satisfactorily in the asymmetric epoxidation step, whereas the epoxidations of the (Z)-isomers were intolerably slow or nonstereoselective. The eryfhro-isomers obtained from the ( )-allylic alcohols may, however, be epimerized in 95% yield to the more stable tlireo-isomers by treatment of the acetonides with potassium carbonate (6a). The competitive -elimination is suppressed by the acetonide protecting group because it maintains orthogonality between the enolate 7i-system and the 8-alkoxy group (cf the Baldwin rules, p. 316). 

In the following example the acetonide protective group is selectively converted to one of two t-butyl groups. The reaction appears to be general, but the alcohol bearing the t-butyl group varies with structure.Benzyli-dene ketals are also cleaved. 

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... 

PREPARATION OF (OH)4- [G2]-C02CH2C6H5 [13]AND GENERAL PROCEDURE FOR THE REMOVAL OF THE ACETONIDE PROTECTING GROUPS... 

As part of a strategy of employing monosaccharides as a convenient source of chirality, organometallic additions to protected L-erythrulose derivatives have been carried out. Employing silyl, benzyl, trityl, and acetonide protecting groups, the diastereoselectivities obtained are discussed in terms of chelation to the a-and/or the /3-oxygen, and are compared with results for similar aldehydes. 

Alternatively, epoxide (3R,5S)-14 was opened regioselectively with lithium iodide on silica [29], The crude product was immediately subjected to acetonide protection, which afforded the desired iodide sy -(3R,5S)-13 with a 58% yield (44% from syn-(3R,5S)-5a Scheme 2.2.7.7). Epoxide (3R,5S)-14 was easily obtained from dihydroxy ester syn-(3R,5S)-5a by treatment with DBU (66% yield) [11]. Treatment of sy -(3R,5S)-5a with LiCN in CH2CI2 gave nitrile (3R,5R)-15 in almost quantitative yield [21]. 

A variation of this route was applied to the preparation of a-methylenecyclo-pentane 179, an intermediate that was employed for the synthesis of prostaglandin PGF2o, (180) (Scheme 6.82). The acetonide-protected oxime-diol 175 [derived from propanal (174)] was treated with sodium hypochlorite without the addition of base. This led to the tricyclic adduct 176 with high stereoselectivity. One of the side chains was subsequently elaborated and the fully protected cyclopentano-isoxazo-line (177), when exposed to Raney Ni/boron trichloride, gave the 2-hydroxymethyl-cyclopentanone (178). This compound was dehydrated using mesyl chloride/ pyridine to furnish enone (179) (324). In another related synthesis of PGF2q, the p-side-chain (3-hydroxyoctenyl) was introduced prior to the cycloaddition (325). 

After removal of the acetonide protecting group the free polyol is obtained as spiroacetal derivative 18. 

Cyclization of the bis-epoxides 123 (mixtures of diastereomers) with benzylamine afforded the azepanes 124 in a preferential 1-endo-tet methodology (Equation 17) <1995JOC5958> however, with the corresponding 3,4-benzyl ethers of the bis-epoxides rather than the // / -acetonide protecting group, no cyclization to six-membered ting species was observed. The azepanes 124 were then converted in two steps to the amino sugar hydrochloride salts 126 via the N-debenzylated intermediates 125 (Scheme 16). 

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. 

A similar observation was made by Marco and coworkers when synthesizing microcarpalide [29]. In the case of the cyclization of acetonide 36, the Z-olefin is the thermodynamic product, produced with the second-generation catalyst G2, while use of Gl gives a 2 1 mixture of E/Z alkenes 37 (Scheme 2.14). These compounds could be separated by chromatography and the E-isomer was subsequently converted to microcarpalide by removal of the MOM and the acetonide protecting groups. 

After extensive optimization of the reaction conditions regarding yield as well as diastereo- and enantioselectivity, we were able to obtain the aldol product 26 with 60% yield and excellent diastereo- and enantiomeric excesses (>99% de, 95% ee). Thus, the simple (S)-proline-catalyzed aldol reaction of 4 with pentadecanal directly delivered gram-amounts of the selectively acetonide protected ketotriol precursor 26 of the core unit of phytosphingosines in excellent stereoisomeric purity (Scheme 7). 

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