Transition state 2,5-dihydrofuran

A number of examples involving nitrile oxide cycloadditions to cyclic cis-disubstituted olefinic dipolarophiles was presented in the first edition of this treatise, notably to cyclobutene, cyclopentene, and to 2,5-dihydrofuran derivatives (15). The more recent examples discussed here also show, that the selectivity of the cycloaddition to 1,2-cis-disubstituted cyclobutenes depends on the type of substituent group present (Table 6.8 Scheme 6.41). The differences found can be explained in terms of the nonplanarity (i. e., pyramidalization) of the double bond in the transition state (15) and steric effects. In the cycloaddition to cis-3,4-diacetyl-(197) and cis-3,4-dichlorocyclobutene (198), the syn-pyramidalization of the carbon atoms of the double bond and the more facile anti deformability of the olefinic hydrogens have been invoked to rationalize the anti selectivity observed. 

A simple procedure to prepare 5-aryl- and 5-pyridyl-2-furaldehydes from inexpensive, commercially available 2-furaldehyde diethyl acetal was reported. The reaction proceeded in a four-step, one-pot procedure and the yield of coupling step was usually between 58-91% <02OL375>. A facile route to 3,4-furandicarboxylic acids was developed. DDQ-oxidation of 2,5-dihydrofuran derivatives, which were produced from dimethyl maleic anhydride, furnished the desired esters of furan-3,4-dicarboxylic acid <02S1010>. The furan-fused tetracyclic core of halenaquinol and halenaquinone possessing antibiotic, cardiotonic, and protein tyrosine kinase inhibitory activities was synthesized. Intramolecular cycloaddition of an o-quinodimethane with furan gave the adduct as a single isomer via an enrfo-transition state, which was converted to trisubstituted furan by oxidation-elimination reactions <02T6097>. 

There is no doubt that such a ketocarbene is expected to be a 1,3-dipole, as discussed in Section 6.2, but the process 8-52 is not a carbeno/rf reaction, as shown in Doyle s general scheme 8-46. The dihydrofuran syntheses are, therefore, only apparently dipolar cycloadditions. Doyle et al. (1984 b) suggested a mechanism for these cycloadditions that is closely related to his explanation of the preferential trans-stereoselectivity in cyclopropanation by a-carbonylcarbenes. One argument of Doyle for this conclusion is the close analogy between the results of dihydrofuran formation of 1- and 2-methoxybuta-l,3-diene with ethyl 3-diazo-2-oxopropionate (8.110) and the cyclopropanation of these butadiene derivatives with ethyl diazoacetate (Doyle et al., 1981, and other papers see Maas, 1986, p. 97). We return, therefore, to the transition state of cyclopropanation (8.105) here in order to investigate whether it is consistent with the mechanism of formation of dihydrofuran. 

Doyle s transition state for the cyclopropanation of alkenes with ethyl diazoacetate is a basis for the apparently completely different reaction with diazocarbonyl compounds that leads to dihydrofurans. Structure 8.105 shows the cyclopropanation process after the reaction of diazoacetate with a transition-metal complex. The essential phenomenon is that, as a nucleophile, the carbonyl group of the diazoacetate in-... 

As mentioned above, dihydrofurans were not found in reactions of diazoacetates with alkoxyalkenes. This observation was the basis for Doyle et al. (1984 b) to postulate that increased stabilization of the bond between the O-atom of the carbonyl group and the electrophilic center of the original alkene will favor formation of the dihydrofuran products. This is shown in Scheme 8-53, which is a bifurcation aft the transition state 8,105. 

The main isomerization products of 2,3-dihydrofuran are cyclopropane carboxalde-hyde (reaction (1)) and propenyl aldehyde (reaction (2)) [76,77]. Propenyl aldehyde can be obtained also via isomerization of the product—cyclopropane carboxaldehyde (reaction (3)). Reactions (1) and (2) go directly from the reactant to the product via one transition state. Reaction (3) has one intermediate and two transition states. The transition state for the production of cyclopropane carboxaldehyde (reaction (1)) involves a C(sp )—O bond cleavage and formation of a new C=0 double bond with the second adjacent carbon atom, together with a C—C bond formation (Figure 6.12). 

An additional reaction in 2,3-dihydrofuran, and the only reaction in 2,5-dihydrofiu-an, is H2 elimination to yield furan [80-84]. In 2,5-dihydrofuran the mechanism is rather simple, one transition state and no intermediates. The two hydrogen atoms come close to one another to form a six-center transition state and produce furan and hydrogen molecule. The barrier is approximately 49kcal/mol. This is shown in Figure 6.14. 

The stereochemical result of the Povarov reaction is closely linked to the applied alkene species. In the case of an acyclic alkene, the 2,4-cis product is highly favored because of a bis-equatorial arrangement of both residues in the transition state. Cyclic alkenes generate predominantly the exo product. However, 2,3-dihydrofuranes and dihydropyrroles give poor diastereomeric ratios (endolexo 1 1-1 2), while 3,4-dihydro-27/-pyranes give excellent ra-... 

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