Alkenes oxabicyclic

Among recently described new Pd-catalysed enantioselective reactions, the ring opening of meso oxabicyclic alkenes with dialkyl zinc reagents in the presence of chiral P/P and P/N ligands reported by Tautens el al. constitutes a synthetically outstanding C-C bond-forming desymmetrization reaction. 

Rhodium catalysts have also been used with increasing frequency for the allylic etherification of aliphatic alcohols. The chiral 7r-allylrhodium complexes generated from asymmetric ring-opening (ARO) reactions have been shown to react with both aromatic and aliphatic alcohols (Equation (46)).185-188 Mechanistic studies have shown that the reaction proceeds by an oxidative addition of Rh(i) into the oxabicyclic alkene system with retention of configuration, as directed by coordination of the oxygen atom, and subsequent SN2 addition of the oxygen nucleophile. 

While transition metal-catalyzed hydroboration is a well-established reaction, the same cannot be said for the transition metal-catalyzed hydroalumination. The synthetic utility of this reaction is only just beginning to emerge. Lautens has led the way in the use of hydroaluminations as the key step in the total synthesis of complex natural products. The synthesis of the anti-depressant sertraline130 involved the formation of the tetrahydronaphthalene core, and this is best achieved using the nickel-catalyzed hydroalumination of oxabicyclic alkenes (Table 16). 

Lautens also used this nickel-catalyzed hydroalumination methodology in the total synthesis of ionomycin 145. The starting compound was a [3.2.1]oxabicyclic alkene 143.144 Their rigid bicyclic structures can be used to introduce functional groups in a highly stereoselective manner. The synthesis of the key intermediate 144 involves the slow addition of DIBAL to the oxabicyclic alkene and the Ni(COD)2/(6T)-BINAP in toluene to afford 144 in 95% yield and 93-95% ee. (Scheme 18). 

Figure 3.44. Scope of Rh/47-catalyzed asymmetric ring-opening of oxabicyclic alkenes with organoboronic acids.

Enantioselective alkylative ring opening of these oxabicyclic alkenes has also been studied. Lautens and coworkers discovered that palladium complexes efficiently catalyze the addition of organozinc reagents to these activated alkenes with concomitant ring opening. In the presence of (Tol-BINAP)PdCl2, diethylzinc adds to oxabenzonor-... 

Based on this model, the regiochemical outcome of both oxabicycHc alkenes and vinyl epoxides can be explained by the relative stability of the two cr-intermediates. With oxabicyclic alkenes intermediate 41 is generated directly and then goes on to give product, whereas with the vinyl epoxides a more highly strained intermediate 40 is first produced which must first isomerize to 41 prior to product formation. The regiochemical outcome with each substrate may therefore arise from the commonahty of a cr-in-termediate 41 to both reaction pathways (Scheme 9.13). 

Scheme 9.12 (a) exo-coordination of the oxabicyclic alkene (b) oxidative insertion... 

In the same year, Nakamura and coworkers published an iron-catalyzed ring opening reaction of oxabicyclic alkenes by Grignard reagents (Scheme 51). This reaction is highly regio- and stereoselective. 

However, examples of Pd-catalyzed carbozincation appear to be limited so far to appropriately substituted oxabicyclic alkenes. 

In the presence of Ni(dppe)Br2 the oxabicyclic alkenes 693 react with propynoic esters to yield 2H-benzo[ ]coumarins 696 (Scheme 172) <2001AGE1286>. The reaction mechanism involves cyclometallation of the propynoic ester and oxabicyclic alkene 693 to form the nickelacyclopentene intermediate 694. (3-Oxy elimination then forms the intermediate 695, which undergoes protonation and isomerization of the double bond followed by intramolecular lactonization to afford the desired 2/7-benzo[ ]coumarins 696 (Scheme 172) <2001AGE1286>. 

Similarly, Ni(dppe)Br2 catalyzes the reaction of (l-iodo-(Z)-propenoates and 2-iodobenzoates 697 with oxabicyclic alkenes 698 to afford 277-benzo[ ]coumarins (Equation 279) <20030L4903>. 

The addition of arylboronic acids to oxabicyclic alkenes yielded ring-opening products via insertion-elimination process.979,980 Chiral DPPF-P(/-Bu)2 was identified as the ligand giving the best reactivity and enantioselectivity (Equation (221)). 

Transition metal-catalyzed enantioselective ring-opening reactions of oxabicyclic alkenes 03ACR48. 

Phenols are used as the nucleophile in the asymmetric aUylation of 7r-aUylpalladium complexes. Trost and Toste attained asymmetric phenyl ether formation in high enantiomeric excess (ee) using diphosphine ligand derived from chiral 1,2-cyclohexanediamine (equation 10). Dynamic kinetic resolution of the racemic secondary aUylic carbonate is conducted in the presence of tetrabutylammonium chloride, which increases the rate of ft—a—ft isomerization of the jr-allyl palladium intermediate (equation 11). Lautens and coworkers cleaved meio-oxabicyclic alkenes with phenol in the presence of a catalytic amount of a chiral ferrocenyldiphosphine and a rhodium complex (equation 12). ... 

Fohlisch found that treatment of 8-oxabicyclo[3.2.1]oct-6-en-3-ones with TMSOTf and triethylamine generates tropones in one step [33 b]. Thus, oxabicyclic alkene 219 was converted in one step to 2-methoxytropone 220, which is... 

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... 

D. S. Millward, G. Sammis, and R. W. Waymouth, Ring-opening reactions of oxabicyclic alkene compounds Enantioselective hydride and ethyl additions catalyzed by group 4 metals, J. Org. Chem., 65 (2000) 3902-3909. 

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>. 

Asymmetric arylative ring-opening of oxabicyclic alkenes bearing dihy-drofuran units has been previously achieved with good enantioselectivity... 

The hydroalumination of oxabicyclic alkenes has been developed as a novel enantioselective entry to cycloalkenols (Scheme 3-86). " Catalysts derived from Ni(cod)2 and BINAP efficiently catalyze the asymmetric hydroalumination of DIBAL-H to various oxabicyclic alkenes. Initial alkene hydroalumination is followed by ring opening of the intermediate organoaluminum to produce cyclohexenol or cycloheptenol products. 

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. 

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