Ketals selective reduction

With cyclic acetals and ketals, selective reductions allow the blocked hydroxy groups of the diol to be deprotected one at a time, a matter of some importance in carbohydrate chemistry. Although there have been a few studies of stereoselective reductions at the masked carbonium center of chiral ketals, more has been done with the formally related reactions in which C—C bonds are formed stereoselectively. ... 

In certain cases, the selective protection of the closely similar sites offers an opportunity to achieve a reversal in selectivity from a common precursor. Thus, the monoketal derivative 228 (Scheme 2.94) can easily be prepared from the respective diketone owing to the steric shielding of the C-17 carbonyl. The opportunity, now, to reduce the non-protected carbonyl in 228 to form alcohol 229 should not be a surprise. However, it is truly remarkable that a selective reduction can also be achieved at the C-3 protected carbonyl. This paradoxical result is due to the utilization of the reagent H2Sil2, which selectively attacks the ketal moiety and induces its removal coupled with a reduction to form the iodo derivative 230. A successful and nearly quantitative reductive conversion at either C-17 or at C-3 is achieved in this manner. In this example, the protected carbonyl functionality served as a non-conventional functional group with a pattern of reactivity sharply differing from that of the unprotected group,... 

This is due to a rapid and selective transformation of aldehydes under these conditions to ketals or hemiketals, which are not reduced (Figure 3.7). The same type of situation permits the relatively rapid formation of ketals of unhindered ketones in the presence of HC(OEt)3, whereby the selective reduction of the most hindered ketone group of 3.13 is possible [GLl] (Figure 3.7). 

After conversion to 19 (70% yield) via Nef reaction and ketalization, selective modification of the terminal olefin by reaction with LAH-TiCl4, quenching with I2, and displacement of the resulting terminal halogen with ethyl acetoacetate anion afforded 20 in 48% overall yield. Deacetylation with sodium ethoxide followed by deketalization under acidic conditions produced an 88% yield of keto ester 21. Seco acid 6 was then obtained (in 29% yield from 18) after reduction of the ketone and ester hydrolysis. Clearly, the significance of this... 

Takei utilized a furan as the synthetic equivalent of a 1,4 dicarbonyl compound in his synthesis of pyrenophorin as described in Scheme 4.6. ° Thus butenolide 28, obtained by Michael addition of butenolide 27 to methyl vinyl ketone, was silylated to provide the silyloxyfuran. Treatment with lead tetraacetate followed by aqueous hydrolysis gave 29 in 55% yield. Protection of the ketones as dimethyl ketals followed by selective removal of the C-7 ketal and reduction gave seco acid 30. Dimerization and hydrolysis gave a mixture of 9 and 18 (17% from 29). 

A very elegant stereoselective synthesis of juvenile hormone has been achieved by Johnson and co-workers,who employed the olefinic ketal Claisen reaction to great advantage. Thus, the hydroxy-ester (15), on treatment with the olefin-ketal (16) in acidic medium was converted into the ester (17). Sodium borohydride reduction to the corresponding allylic alcohol and a second Claisen-reduction sequence as described above yielded the trienol-ester (18). Chlorination under Sni conditions and selective reduction of the resultant primary allylic chloride produced the well-known triene-ester (19) which was converted to juvenile hormone (11). 

Selective reduction of 71 with lithium 9b-boraperhydrophenalyI hydride afforded a 70 30 mixture of a-(axial) 72 and -(equatorial) alcohols. Due to the lability of the a-alcohol to ketal formation (73), the crude mixture was transformed directly into the methoxycyclopropane (74). Protolysis yielded the ketoalcohol (75), which was transformed into the decalone 76 by Wolff-Kishner reduction of the ketone, followed by oxidation of the alcohol. The stereochem-... 

Also noteworthy was the dependence of the ketal yield upon the choice of lanthanide salt. Lighter lanthanide ions (Ce ", Nd " " - softer Lewis acids) having larger ionic radii were preferred in cases where the aldehyde-ketone discrimination became more difficult. Several examples were cited by the authors, and the subject of selective reduction of ketones in the presence of aldehydes is treated in section 5.2. 

A convenient new one-pot procedure for the selective reduction of ketones in the presence of aldehydes (the less usual chemoselectivity) is outlined in Scheme 9. ° The aldehyde is protected as an imine and the ketone is then reduced in situ with a hindred hydride reagent the aldehyde is regenerated on hydrolytic work-up. Conjugated and aromatic aldehydes are protected satisfactorily by this sequence, and moderate discrimination between aliphatic and aromatic aldehydes, with preferential reduction of the aromatic aldehyde, can also be achieved. These authors claim better selectivity than previous methods based on ketalization or hydration of aldehydes with lanthanoid cation catalysts (4,141). 

A carbonyl group cannot be protected as its ethylene ketal during the Birch reduction of an aromatic phenolic ether if one desires to regenerate the ketone and to retain the 1,4-dihydroaromatic system, since an enol ether is hydrolyzed by acid more rapidly than is an ethylene ketal. 1,4-Dihydro-estrone 3-methyl ether is usually prepared by the Birch reduction of estradiol 3-methyl ether followed by Oppenauer oxidation to reform the C-17 carbonyl function. However, the C-17 carbonyl group may be protected as its diethyl ketal and, following a Birch reduction of the A-ring, this ketal function may be hydrolyzed in preference to the 3-enol ether, provided carefully controlled conditions are employed. Conditions for such a selective hydrolysis are illustrated in Procedure 4. 

Dehydration of cortisone (198) affords the diene 199. This is then converted to ketal 200. The selectivity is due to hindrance about both the 11- and 20-carbonyl groups. The shift of the double bond to the 5,6-position is characteristic of that particular enone. Treatment of protected diene 200 with osmium tetroxide results in selective oxidation of the conjugated double bond at C-16,17 to afford the cis-diol (201). Reduction of the ketone at C-ll (202) followed by hydrolysis of the ketal function gives the intermediate 203. Selenium dioxide has been... 

The selective organosilane reduction of ketone functions can be effected in the presence of a number of other functional groups including epoxides,320,366 ketals,86,367 thioketals,368 other ketones,369,370 /1-lactams,371 alkynes,372 esters,79,80,83,84,87,320,373,374 a-bromides,76,80,83 amides80,83,84,86,276,320,375... 

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