Isopropylidenated dienophiles

For the other isopropylidenated dienophiles 9, 10, and 12, separation of the product isomers was more difficult, but determination of the ratios of the four possible products as before gave the results shown in Table II. 

However, with these isopropylidenated dienophiles, the diastereofacial selectivity was much higher than with the acetylated analogues, especially in the ribo and Ivxo isomers, a factor of importance in any proposed application in chiral synthesis. 

When comparing these results with those previously obtained using carbohydrate-based vinyl ethers as chiral dienophiles, this improved facial diastereoselectivity to heterodienes under similar conditions is noteworthy.81 The efficient chiral transfer in the second example might mostly be attributed to the specific architecture of the l,2 5,6-di-0-isopropylidene-a-D-glucofuranose moiety.Those findings open the way to develop well-defined spiro-carbohydrate templates towards improved auxiliaries for chirality transfer in a wide range of syntheses. 

The dienophile can approach the face of isodicyclopentadienes 32 (tricyclo[5.2.1.02 6]deea-2,5-dienes) from above or below the plane of the eyclopentadiene, so providing adducts 33 with the antisesquinorbornene skeleton (vr/j-isomer) The anti-isomers are generally the exclusive products unless spiro-cyclopropane and isopropylidene substituents are present at C-10, so that loss or complete inversion of diastereoselectivity is observed. 

Dienophiles carrying a sugar moiety as a face-directing element may also benefit from chelation. Two recent examples are depicted in Scheme 97. Treatment of the 5-0,6-0-disilylated 3-(7-acryloyl-1,2-0-isopropylidene-a-glucofuranose (400) with TiCU gave a complex which was assigned chelate structure... 

The use of an acetal to tether the diene and dienophile has been investigated by Craig and co-workers [15], Preparation of the unsymmetrical acetal precursor was best achieved via the corresponding enol ether. For example, the isopropylidene-linked triene 28 was synthesized in two steps from acetate 29. Tebbe methylenation of 29 afforded enol ether 30, which was used directly in a Pd -catalyzed addition of the dienophile 3 to form 28 (acid-catalyzed addition with pTSA proved inferior). Thermolysis of 28 in toluene at 165°C allowed a remarkably facile and completely regiospecific cyclization to take place. Acidic methanolysis of the Diels-Alder adducts resulted in cleavage of the tether and isolation of a 2.7 1 mixture of lactones 31 and 32 in 72% yield (Scheme 10-9). 

Related trans dienophiles were prepared by the same direct Wittig reaction on the free aldopentoses but with an acetonation step in place of acetylation thus prepared were the 4,5 6,7-di-0-isopropylidene analogue (9) of 5 (yield 29%), the analogue 10 of 6 (20%), the analogue 11 of 7 (34%), and the analogue 12 of 8 (18%). 

On the contrary, if the reactivity of the dienophile complex is enhanced, a higher stereoselection can be expected. Actually, the titanium complex 3 of the 3-0-acryloyl-l,2-0-isopropylidene-a-D-xylofuranose, in which the titanium carries three chlorine ligands, with cyclopentadiene forms only one diastereomer 4 of the Diels-Alder adduct. As confirmed by reductive cleavage, only the expected (R)-diastereomer is obtained. The other diastereomer is not detectable by 400 MHz-NMR spectroscopy of the crude hydrolyzed reaction mixture (23). 

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