Enantioselective synthesis of bis(γ‐butyrolactones). Their oxidative degradation to tetraols as a key step in stereoselective syntheses of 1,3,5,7,9‐pentaol synthons for polyhydroxylated natural products

Abstract

The syntheses of two enantiopure skipped-chain pentaol building blocks 51 and 56 are described. They are based on a strategy which derives 1,3,?,9-tetraols from bis(y-butyrolactones). Two equivalents of y-lactone 17, readily available from L-glutamic acid, and one equivalent of the diiodoisobutene 22 furnished bis(y-butyrolactone) trans,trans-21 stereoselectively in a single step. The same lactone, combined in a 2 : l ratio with the dibromoisobutene derivative 18, led in four steps and with good stereocontrol to the isomeric bis(ylactone) cis,trans-21. On the basis of the lH-and 13C-NMR spectral data of these and other lactones it was possible to distinguish 1,343-and 1,3-trans-disubstituted y-lactones. Each of the bislactones was subject to a Criegee rearrangement of derived bis(peroxosu1fonates) to give the diastereomerically pure 1,3,?,9-tetraols 26 and 31. The configuration of these tetraols was proven by the 13C-NMR shifts of the corresponding bis(acetonides) 27 and 32. Ozonolytic cleavage of the C=C bond of 27, reduction of the obtained ketone 28 to alcohol 29, acetonide rearrangement under thermodynamic control (-. 30), and fuctionalization of the liberated hydroxy group delivered the end group-differentiated 1,3,5,?,9-pentaol building block 51. It represents a segment of the polyol parts of the antibiotics roxaticin (52) and mycoticin (53). The oxidative cleavage of the C=C bond of bis(acetonide) 32 and chelation-controlled reduction of the resulting ketone 33 with Zn(BH& furnished after acetonide migration and functionalization of the unprotected hydroxy group the all-syn-configured 1,3,5,?,9-pentaol building block 56. The latter compound should provide an entry into total syntheses of the naturally occurring poly(methy1 ethers) 57 and 58.

Bidirectional Asymmetric Allylboration. A Convenient Asymmetric Synthesis of C2-Symmetric 3-Methylenepentane-1,5-diols and Rapid Access to C2-Symmetric Spiroketals

“…Careful chromatography afforded the C 2 -symmetric spiroketal 25 (58%), accompanied by three other diastereoisomers (two inseparable) which could not be identified (25% combined). The stereochemistry of the spirocenter in 25 was assigned by analogy with that observed in the spirocyclization of a number of closely related compounds, − and is supported by the fact that the signal for the hydroxyl protons in the 1 H NMR spectrum appears at δ 4−4.3 ppm, which has been shown to be diagnostic for an axial hydroxyl proton in related systems …”