Diol protection isopropylidene

Condensation of 2,3-O-isopropylidene-D-glyceraldehyde-A -benzylimine 211 with 2-(tri-methylsilyloxy)furan in the presence of a Lewis acid generates a mixture of butenolides 212 that is converted into D-nZ 6>-A, A -diprotected derivative 213 in 68% yield (Scheme 13.67) [119]. Dihydroxylation of 213, followed by diol protection and lactone reduction, furnishes the 5-amino-5-deoxyheptose derivative 214. Hydrogenolysis in MeOH generates 215 and its deprotection furnishes enantiomerically pure l,5-dideoxy-l,5-imino-D-g/yc r6>-D-a//6>-heptitol 216 [120]. 

Dithiols, like diols, have been protected as 5,5 -methylene, 5,5 -isopropylidene, and 5,5 -benzylidene derivatives, formed by reaction of the dithiol with formaldehyde, acetone, or benzaldehyde, respectively. The methylene and benzylidene derivatives are cleaved by reduction with sodium/ammonia. The isopropylidene and benzylidene derivatives are cleaved by mercury(II) chloride with sodium/ ammonia the isopropylidene derivative is converted to a monothio ether, HSCHR-CHRSCHMe2- ... 

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. 

Isopropylidene acetals are convenient protecting groups in carbohydrate chemistry, particularly for the protection of 1,2- and 1,3-diols, and are readily formed by reaction of the diol with acetone or 2,2-dimethoxypropane under acidic conditions. Several protic and Lewis acids have been reported as catalysts for this purpose.98... 

Diastereoselective reduction of the aldol 221/ can be achieved using AIH3 in toluene at —78°C. The corresponding ra-diol is preferentially formed. The diol can be protected with isopropylidene acetal to provide tricyclic compound 222. This can be converted to conformationally rigid C-l ketone 223 by deprotection of the PMB group and successive oxidation with PDC (Scheme 7-73). 

For the cw-dihydroxylation of protected lL-l,2 3,4-di-0-isopropylidenecyclohex-5-ene-l,2,3,4-tetrol (22g) to the diol lD-l,2 3,4-di-0-isopropylidene-a/to-inositol by RuClj/aq. Na(IO )/EtOAc-CH3CN/0°C cf. 3.1.2.1 and Fig. 3.3 [347]. Oxygen insertion by stoich. RuO /CCl occurred in addition to the secondary alcohol oxidation of the five-membered ring 5-0-benzoyl-l,2-0-isopropylidene-a-D-xylofnranose, giving the six-membered ring l,2-0-isopropylidene-6-0-benzoyl-3-oxa-a-D-e/7fftro -4-hexulopyranose-a-D-xylofuranose [325]. 

Carbapentofuranoses could be obtained by periodate cleavage of an exocyclic diol in the isopropylidene protected carba hexofuranoses, as illustrated for 72. The protected carba pentofuranose 75 was obtained and deprotected to give carba- -D-lyxofuranose (76). 

Alkylidene protecting diols Remain unchanged isopropylidene,40 benzylidene,41 cyclohexylidene42 ... 

Benzylidene and isopropylidene acetals are often used for the selective protection 1,2-cis or 1,3-cisjtrans diols of sugar derivatives. They are stable to strong basic conditions but quite fragile towards acid. Recently, dispirodiketal and cyclohexane-1,2-diacetal groups have been introduced to protect selectively 1,2-trans diols of carbohydrates. 

Benzylidene and isopropylidene acetals of irons-1,2-diols are very labile as a result of ring strain and are not often used for synthetic applications. Fortunately, the protection of these diols can be accomplished with the recently developed dispiroketal (dispoke)35 and cyclohexane-1,2-diacetal (CDA) groups.36... 

In order to prevent competing homoallylic asymmetric epoxidation (AE, which, it will be recalled, preferentially delivers the opposite enantiomer to that of the allylic alcohol AE), the primary alcohol in 12 was selectively blocked as a thexyldimethylsilyl ether. Conventional Sharpless AE7 with the oxidant derived from (—)-diethyl tartrate, titanium tetraisopropoxide, and f-butyl hydroperoxide next furnished the anticipated a, [3-epoxy alcohol 13 with excellent stereocontrol (for a more detailed discussion of the Sharpless AE see section 8.4). Selective O-desilylation was then effected with HF-triethylamine complex. The resulting diol was protected as a base-stable O-isopropylidene acetal using 2-methoxypropene and a catalytic quantity of p-toluenesulfonic acid in dimethylformamide (DMF). Note how this blocking protocol was fully compatible with the acid-labile epoxide. 

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