Oxo-ene reaction

Alkenamides react with trioxane in triflic acid to yield 3,6-dihydro-2/7-pyran derivatives693 [Eq. (5.249)]. An oxo-ene reaction to form a homoallyl alcohol... 

Trifluoromethanesulfonic acid can mediate the condensation of alkenamides 275 with t-trioxane to afford 3,6-dihydropyrans 276. The reaction proceeds via two oxo-ene reactions to afford the intermediate diol 277, which undergoes cyclodehydration to form the desired dihydropyrans (Scheme 70). This methodology can provide a route to the regioisomeric dihydropyran 278 by simple modification of the starting alkenamide (Equation 127) <1997TL9057>. 

Dihydropyrans. Either by cycloaddition of dienes with aldehydes (electron-rich aldehydes not suitable) or by sequential oxo-ene reaction, the synthesis is catalyzed by TfOH. 

The first step 202 is now a pericyclic reaction. It looks like a cycloaddition, though it involves a hydrogen transfer as well. It is in fact a carbonyl (or oxo- ) ene reaction. It is like a Diels-Alder cycloaddition in which a C-H bond has replaced one of the double bonds in the diene and a C=0 group is the dienophile. Many Prins reactions are probably carbonyl ene reactions. In his excellent review30 in Comprehensive Organic Synthesis, B. J. Snider says The (carbonyl) ene reaction and the Prins reaction are not mechanistically distinct . Though this step is pericyclic, it is very polar and the transition state 203 no doubt contains partial charges. It is therefore stabilised and the reaction accelerated by protic acids 205 and Lewis acids 207. 

It is less common to find two pericyclic reactions of the same kind coupled together but the Alder ene reaction and the oxo ene reaction can both be catalysed by Lewis acids under the same conditions. A simple example is the combination of the exocyclic alkene 157 with acrolein. The intermediate unsaturated aldehyde 158 cyclises stereoselectively to form a new carbocyclic ring 159. The intermediate 158 is perfectly stable so the tandem sequence is convenient rather than necessary.22... 

The mono adduct of substituted furans, e g., of 2-methylfuran (6) aromatizes under the reaction conditions to a tetrachloroben-zylcarbonyl compound via a retro-oxo-ene reaction (eq 10). The high bond energy of the carbonyl group drives this process, that does not occur with the analogous mono adduct of pyrroles and thiophenes. ... 

Mikami and co-workers16-19 have done extensive work for developing catalysts for the asymmetric carbonyl-ene reaction. Excellent enantioselectivites are accessible with the binol-titanium catalyst 17 (Equation (10)) for the condensation of 2-methyl butadiene (R1 = vinyl) and glyoxalates (binol = l,T-binaphthalene-2,2 -diol).16 The products were further manipulated toward the total synthesis of (i )-(-)-ipsdienol. The oxo-titanium species 18 also provides excellent enantioselectivity in the coupling of a-methyl styrene with methyl glyoxalate.17 Reasonable yields and good enantioselectivites are also obtained when the catalyst 19 is formed in situ from titanium isopropoxide and the binol and biphenol derivatives.18... 

Abstract Aldehydes obtained from olefins under hydroformylation conditions can be converted to more complex reaction products in one-pot reaction sequences. These involve heterofunctionalization of aldehydes to form acetals, aminals, imines and enamines, including reduction products of the latter in an overall hydroaminomethylation. Furthermore, numerous conversions of oxo aldehydes with additional C.C-bond formation are conceivable such as aldol reactions, allylations, carbonyl olefinations, ene reactions and electrophilic aromatic substitutions, including Fischer indole syntheses. 

Depending on the type of iron catalyst, the reaction seems to take different mechanistic pathways. According to Johannsen and Jorgensen s results, the catalytic cycle starts with the formation of nitrosobenzene 32 either by disproportionation of hydroxylamine 29a to 32 and aniline in the presence of oxo iron(IV) phthalocyanine (PcFe4+=0) or by oxidation of 29a [131]. The second step, a hetero-ene reaction between the alkene 1 and nitrosobenzene 32, yields the allylic hydroxylamine 33, which is subsequently reduced by iron(II) phthalocyanine to afford the desired allylic amine 30 with regeneration of oxo iron(IV) phthalocyanine (Scheme 3.36). That means the nitrogen transfer proceeds as an off-metal reaction. The other byproduct, azoxybenzene, is probably formed by reaction of 29a with nitrosobenzene 32. 

The formation of tetrahydropyrans by the Prins reaction The oxo-ene mechanism Stereoselectivity in the Prins reaction... 

The first step is a straightforward ene reaction 160 with the LUMO of the aluminium complex of acrolein attracting the HOMO of the reactive alkene. The circles indicate the largest coefficient in each frontier orbital. The second step is an oxo-ene 161 with the oxygen atom of the aldehyde capturing the allylic proton. The stereochemistry of the product 159 suggests that the reactive conformation is 161. 

Both enantiomers of binaphthol have found many uses as chiral reagents and catalysts. Thus, they modify reducing agents (e.g., lithium aluminum hydride) for the reduction of ketones to chiral secondary alcohols (Section D.2.3.3.2.) or react with aluminum, titanium or boron compounds to give chiral Lewis acids for asymmetric Diels-Alder reactions (Section D. 1.6.1.1.1.3.) and ene reactions (Section D.I.6.2.). They have also been used as chiral leaving groups in the rearrangement of allyl ethers (Section D.l.1.2.2.) and for the formation of chiral esters with a-oxo acids (Section D. 1.3.1.4.1, and many other purposes. 

---