Applications oxabicyclic

Furan is an excellent diene in a wide variety of Diels-Alder reactions, providing oxabicyclic compounds with useful synthetic applications. However, Diels-Alder reactions with furans are often reversible and require a highly reactive dienophile in order to provide useful yields of the cycloadduct. As shown in Scheme 17, furans have now been shown to undergo synthetically useful Diels-Alder reactions with azirines. The reaction of furan with azirine 91 provides cycloadduct 92 in 100% yield <1998J(P1)299>. Aziridine 92, while crystalline, is moisture sensitive, decomposing to aziridine 93. An X-ray structure of 92 was obtained which confirmed the exo-natute of the cycloaddition reaction in contrast to the r/o-cycloadditions seen in the formation of 88 <2001J(P1)2969>. 

In this review, methods for the construction of oxabicyclic substrates of general structure 1, Fig. 1, are described as well as ring opening reactions which are applicable to the synthesis of natural products. 

Lautens M, Fagnou K, Yang D (2003) Rhodium-catalyzed asymmetric ring opening reactions of oxabicyclic alkenes applications of halide effects in the development of a general process. J Am Chem Soc 125 14884-14892... 

Synthetic applications of 8-oxabicycloL3.2.1Joct-6-en-3-one were reviewed <04AG(E)1935>. Ruthenium-catalyzed [2+2] cycloaddition of oxabicyclic alkenes with a chiral acetylenic acyl sultam provided the cycloadduct with excellent diastereoselectivity and enantioselectivity. An example is shown in the scheme below <04AG(E)610>. 

Opening of oxabicycles. The Syv2 reduction opens the 2,5-dihydrofuran unit. Usually the presence of an endo-OH is required to assist the transformation. This method is applicable to the elaboration of the C17-C2J segment of ionomycin. 

The nickel-catalyzed hydroalumination of alkenes has been extensively investigated in a variety of contexts. The interaction of aluminum hydrides with nickel(0) and the mechanism of alkene hydroalumination has been studied in detail by Wilke, Eisch, and Zweifel. The most extensive synthetic applications from Lautens involve the hydroalumination of oxabicyclic alkenes followed by ring opening to produce substituted cyclohexenes and cycloheptenes (Scheme 74). - An as5mimetric variant emplo5dng 2,2 -bis(diphenylphosphino)-l,l -binaphthyl (BINAP) is also quite general for various oxabicyclic starting materials. 

In 2007, Hoveyda and Gillingham disclosed the total synthesis of (+)-baconipyrone C (143), which represents the first, and a rare example of, application of a Ru-catalyzed alkene ROM/RCM to complex natural product synthesis (Fig. 38) [90]. By treatment of oxabicycle (144) with 2 mol% chiral Ru carbene catalyst, the key highly functionahzed pyran intermediate (145) was prepared in 63% yield and 88% ee. Notably, the chiral catalyst was generated in situ by subjection of... 

In 1993, Corey and Loh first reported the application of a catalytic enantioselective cycloaddition to fiiran [53]. In the presence of 10mol% of the oxazaborolidine-derived chiral catalyst 74, 2-bromo- and 2-chloroacrolein smoothly underwent cycloaddition (—78°C, 5h) with fiiran to give the cycloadducts 75a,b in >98% chemical yield (exolendo 99 1) with 96 4 and 95 5 enantioselectivity, respectively. The iV-tosylcarboxylic acid precursor of the chiral catalyst could be efficiently recovered for reuse in each case. Bromo derivative 75a served as a valuable precursor for the preparation of a variety of interesting oxabicycles, such as 76-78, in enantiomerically pure form (Scheme 13.23). 

Ru-catalyzed AROM/CM sequences served as a key step in the total synthesis of baconipyrone C (163, Scheme 24.42), a marine polyketide isolated from Siphonaria baconi The employed Ru carbene [Ru]-VI is generated in situ by treatment of the achiral Ru-PCya complex with Ag-based V-heterocyclic carbene (NHC) and Nal. And then, the [Ru]-VI-catalyzed AROM/RCM of oxabicycle 161 with styrene (8 equiv) afforded the fully substituted pyran 162 in 62% yield and in 88% ee. The additional transformations led to 163 in good overall yield. Although this application of AROM/CM process to 161 was the first and rare example of Ru-catalyzed enantioselective olefin metathesis process, very recently, an application of enantioselective RCM reaction catalyzed by [Ru]-VII to the synthesis of (—)-5-e/>/-citreoviral has been reported by Funk. ... 

One important field of application of the NHC in transition metal-catalysed reactions is obviously the olefin metathesis. Among the various applications described, one can notice the nice use of complex (15) to affect the desymmetrization of oxabicyclic alkenes by a Z-diastereoselective and enantioselective ring opening/cross metathesis with enol... 

Total synthesis of baconipyrone C, summarized in Scheme 12.5 [10], is the first and only application of Ru-catalyzed enantioselective olefin metathesis to natural product synthesis. Treatment of oxabicycle 11 with styrene and 2mol% chiral Ru complex [Ru]-XV [11] leads to the formation of pyran 12 in 62% yield and with an enantiomeric ratio of 94 6. Ru-carbene [Ru]-XV is generated in situ by subjecting the corresponding Ag-based N-heterocyclic carbene (NHC) to an achiral Ru-PCys complex and Nal. It is also worthy of note that the diketone fragment of baconipyrone C was synthesized through a tandem double-allylic alkylation process promoted by a chiral NHC-Cu complex that is structurally related to carbene [Ru]-XV. 

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