Triol selective silylation

Five steps were required to convert 75 into the iodide coupling partner 44 needed for union with dithiane 43 (Scheme 17.16). Thioacetal formation31 and concomitant deketalisation were instigated by reacting 75 with 1,3-propanedithiol under Lewis acid conditions. Triol 76 was isolated in 65% yield. The less-hindered primary hydroxyl of 76 was then selectively 0-tosylated, and the remaining hydroxyls masked as tert-butyldimethyl silyl (TBDMS) ethers. Iodide displacement on 77 with sodium iodide and copper bronze,32 and transketalisation with N-chlorosuccinimide (NCS)/silver nitrate33 finally secured 44. 

Mitsunobu reaction as well as by mesylation and subsequent base treatment failed, the secondary alcohol was inverted by oxidation with pyridinium dichromate and successive reduction with sodium borohydride. The inverted alcohol 454 was protected as an acetate and the acetonide was removed by acid treatment to enable conformational flexibility. Persilylation of triol 455 was succeeded by acetate cleavage with guanidine. Alcohol 456 was deprotonated to assist lactonization. Mild and short treatment with aqueous hydrogen fluoride allowed selective cleavage of the secondary silyl ether. Dehydration of the alcohol 457 was achieved by Tshugaejf vesLCtion. The final steps toward corianin (21) were deprotection of the tertiary alcohols of 458 and epoxidation with peracid. This alternative corianin synthesis needed 34 steps in 0.13% overall yield. 

We referred above to a synthesis of bryostatin that contained a reduction controlled by a 1,3-relationship. Evans synthesis34 contains a 1,3-selective aldol as well as a 1,3-controlled reduction The aldehyde 202, made by an asymmetric aldol reaction, was combined with the double silyl enol ether of methyl acetoacetate to give, as expected, the anti-aldol 203. However, the only Lewis acid that gave this good result was (<-PrO)2TiCl2 and not BF3 thus emphasising the rather empirical aspect of this type of control. Evans s own 1,3-controlled reduction gave the anti,anti-triol 204 that was incorporated into bryostatin. 

Many examples exist wherein a silyl enol ether is deprotected and oxidised in a one-pot procedure using Swem conditions. Godfroid and co-workers report the selective oxidation of primary TMS or TES protected 1,2-diols, 1,3-triols, and polyhydroxy compounds to the corresponding silyloxy aldehydes even when using excess Swem reagents.36... 

The synthesis of 188 from epoxide 189 was done as shown in Scheme 25. Epoxide opening with a propargyl alane reagent [124], protection-deprotection of the alcohol functions, and Redal reduction led to the -allylic alcohol 194, also obtained by another route [116]. Asymmetric epoxidation-Redal epoxide opening [60-62] followed by silylation and debenzylation led to intermediate triol 195. Selective six-membered acetal formation and primary alcohol oxidation then furnished building block 188. 

The protected butane-1,2,3,4-tetraol 15, easily available in three steps from D-tartaric add diethyl ester, was the starting material for the synthesis of (+)-phomopsohde B (Scheme 2.4). Thus, IBX (2-iodoxybenzoic acid) oxidation of the primary alcohol followed by HWE olefination with a chiral phosphonate derived from L-lactic add (not depicted) gave a,fi-enone 16. Stereoselective reduction of the ketone carbonyl and acidic deavage of the acetal moiety furnished triol 17. Selective protection of the two secondary hydroxyl groups was achieved through triple silylation with subsequent selective desilylation of the primary OTBS group. 

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