Trehazolin synthesis compounds

An asymmetric synthesis of aminocyclopentitols 134-137 has been used in the synthesis of trehazolin via free-radical cycloisomerization of enantiomerically pure, alkyne-tethered oxime ethers derived from D-mannose (Scheme 17).84 Treatment of 2,3 5,6-di-(9-isopropylidene-D-mannofuranose (128)85 with ethynylmagnesium bromide gave compound 129, which underwent sequential one-pot acid hydrolysis plus diol cleavage to give 130, oximation of which afforded the radical precursor 131, in 41% overall yield from 129. The free hydroxyl group of 131 was protected as acetate 132 and tert-butyldimethylsilyl ether 133, which were isolated as inseparable... 

Enantioselective total syntheses of (-)-6-epitrehazolin and (+)-trehazolin were achieved by the synthesis of 275, which began with an asymmetric heterocycloaddition between [(benzyloxy)methyl]cyclopentadiene (263),108 prepared from thallous cyclopentadienide, and the acylnitroso compound arising from in situ oxidation of (,S )-mandelohydroxamic acid (264) with tetrabutylammonium periodate. Cycloaddition led to a mixture of 265 and its diastereomer (Scheme 35).109 The inseparable mixture was reduced to afford cyclopentenes 266 and 268 in 40% and 11 % overall yields, respectively, from thallous cyclopentadienide. Catalytic osmylation of 266 favored syn addition, while the osmylation of diacetate 267 was more selective and nearly quantitative, affording, after acetylation, compounds 270 and 269 in >5 1 ratio. 

On the other hand, Carreira et al. also reported the total synthesis of trehazolin from the optically active spirocycloheptadiene [196], which was prepared from the (7 )-epichlorohydrin 282 and lithium cyclopentadienide, shown in O Scheme 41. Treatment of lithium cyclopentadi-enide (CpH+BuLi) with (/J)-epichlorohydrin 282 afforded the optically active spirocycloheptadiene 283 in 91% ee. Compound 283 was converted into trichloroacetimidate 284 by treatment of NaH and CI3CCN [197], and subsequent treatment of 284 with I(. -cohidine)2C104 gave the alcohol 287 via the unstable intermediates 285 and 286. After silylation of the secondary hydroxy group of 287, the imidate underwent nucleophilic opening upon treatment of the corresponding silyl-protected imidate with Li2NiBr4 to yield the cyclopropylcarbinyl bro-... 

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