6,8-Dioxabicyclo octane synthesis

The bromoallene (-)-kumausallene (62) was isolated in 1983 from the red alga Laurencia nipponica Yamada [64a], The synthesis of the racemic natural product by Overman and co-workers once again employed the SN2 -substitution of a propargyl mesylate with lithium dibromocuprate (Scheme 18.22) [79]. Thus, starting from the unsymmetrically substituted 2,6-dioxabicyclo[3.3.0]octane derivative 69, the first side chain was introduced by Swern oxidation and subsequent Sakurai reaction with the allylsilane 70. The resulting alcohol 71 was protected and the second side chain was attached via diastereoselective addition of a titanium acetylide. The synthesis was concluded by the introduction of two bromine atoms anti-selective S -substitution of the bulky propargyl mesylate 72 was followed by Appel bromination (tetrabromo-methane-triphenylphosphine) of the alcohol derived from deprotection of the bromoallene 73. 

Two formal syntheses of (-)- [80] and (+)-kumausallene [81] followed this route and relied on the enantioselective preparation of the 2,6-dioxabicyclo[3.3.0]octane core 69 starting from diethyl tartrate or an appropriate chiral sulfoxide. In contrast, Evans et al. [82] used a distinct biomimetic approach in their enantioselective synthesis of the natural product (-)-62 (Scheme 18.23). 

The kinetics and thermodynamics of the ketalization of dihydroxyketones 145 have been examined (Equation 12) <1997T11179> the major aim of the study was to better understand these kinds of cyclizations for the synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of the zaragozic acids 147. 

Toward the synthesis of zaragozic acids, a novel family of fungal metabolites that has been shown to be picomolar competitive inhibitors of squalene synthease, Hodgson s group and Hashimoto s group have used cyclic carbonyl ylide formation/[3 + 2]-cycloaddition approach. " In Hashimoto s synthesis, the 2,8-dioxabicyclo[3,2,l]octane core... 

A. Warm and P. Vogel, Helv. Chim. Acta 70 690 (1987). An improved synthesis of (lS,4S)-7-oxabicyclo[2,2.1]hept-5-en-2-one starting from a new chiral auxiliary, methyl (1 S,5R,7S)-3-eihyl-2-oxo-3-aza-6,8-dioxabicyclo[3.2.1 ]octane-7- o-carboxylate (obtained from di-O-acetyl-(SyS)-tartaric anhydride and W-ethylaminoethanol ethyl acetal), was reported J.-L. Reymond and P. Vogel, Tetrahedron Asymm. 7 729 (1990). 

The synthesis of the unsubstituted dideoxyisohexide parent compounds was performed by Cope and Shen.196,197 Isomannide dichloride (114) has been converted into D-c/5-2,6-dioxabicyclo[3.3.0]octane (115) by hydrogen-olysis. The L enantiomer 117 was obtained by reaction of D-l,6-diacetoxy-3,4-hexanediol ditosylate (116) with sodium methoxide (see Scheme 25). 

Isosorbide (3) as a starting material from the chiral pool is the educt for the ten-step enantioselective synthesis 73 of ll-deoxy-8-epi-ll-oxaprosta-glandin (150a) and its (15/ ) diastereoisomer (150b) (see Scheme 42). (/ ,/ J-cw-2,6-Dioxabicyclo[3.3.0]octane (115) was the starting compound ... 

Francke W., Schroder F., Kohnle U. and Simon M. (1996a) Synthesis of (lS,2R,5R)-2-ethyl-l,5-dimethyl-6,8-dioxabicyclo [3.2.1] octane, the aggregation pheromone of male beech bark beetle, Taphrorychus bicolor (Col., Scol.). Liebigs Ann. 10, 1523-1527. 

An asymmetric total synthesis of (—)-secodaphniphylline was carried out using a mixed Claisen condensation between (—)-methyl homosecodaphniphyllate (11) and a carboxylic acid derivative 154 with the characteristic 2,8-dioxabicyclo[3.2.1]octane structure commonly found in the daphniphyllum alkaloids (Scheme 18.23) [68,69]. The necessary chirality was secured by an asymmetric Michael addition reaction of... 

Suthers, B.D., Jacobs, M.F., and Kitching, W. 1998. Synthesis and NMR profiling of dioxabicyclo[3.2.1]octanes related to pinnatoxin D. Confirmation of the relative stereochemistry about rings E and F. Tetrahedron Lett. 39, 2621-2624. 

Since the publication of the corresponding chapter in CHEC-II(1996) <1996CHEC-II(3)525>, there have been a large number of developments in the chemistry of 1,3-dioxole systems and these have mainly involved 1,3-benzo-dioxoles 1, 1,3-dioxolanes 2, and the isomeric l,3-dioxolan-2-ones 3 and l,3-dioxolan-4-ones 4. There have been specific reviews on the synthesis of 1,3-dioxolium salts 5 <2002SOS(11)13> and the transformations of the 6,8-dioxabicyclo[3.2.1]octane compounds 6 <2003SL1759>. 

C.H. Heathcock and co-workers devised a highly convergent asymmetric total synthesis of (-)-secodaphniphylline, where the key step was a mixed Claisen condensation. In the final stage of the total synthesis, the two major fragments were coupled using the mixed Claisen condensation] the lithium enolate of (-)-methyl homosecodaphniphyllate was reacted with the 2,8-dioxabicyclo[3.2.1]octane acid chloride. The resulting crude mixture of (3-keto esters was subjected to the Krapcho decarboxylation procedure to afford the natural product in 43% yield for two steps. 

Quideau, S., and Ralph, J. (1993) Synthesis of 4,8-bis(4-hydroxy-3-methoxyphenyl)-3, 7,dioxabicyclo[3.3.0]octan-2-ones and determination of their relative configuration via long-range proton couplings. J. Chem. Soc., Perkin Trans. 1 (6), 653-659. 

A synthesis of 2,8-dioxabicyclo[3.3.0]octan-3-one derivatives consists of conjugate addition of formaldehyde SAMP-hydrazone to a,P-unsaturated 8-valerolactone and a-alkylation, with hydrolytic reorganization of the functional groups. ... 

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