Pericyclic reactions ketenes

Since stepwise reactions are not subject to the rules of pericyclic reactions, they are often invoked to explain how reactions in which the rules have been subverted take place. However, there is a small group of thermal [2+2] cycloadditions that seem to be disobeying the rules, and yet may well be pericyclic. One is the reaction of ketenes with electron-rich alkenes, illustrated by the reaction of diphenylketene 2.167 with ethyl vinyl ether 2.166 giving the cyclobutanone 2.168. Another is a group of electrophile-... 

Asymmetric Pericyclic Reactions. Several reports illustrate the utility of fra/is-2,5-dimethylpyirolidine as a chiral auxiliary in asymmetric Claisen-type rearrangements, [4 + 2], and [2 + 2] cycloaddition reactions. The enantioselective Claisen-type rearrangement of N,0-ketene acetals derived from tram-2,5-dimethylpyrrolidine has been studied. For example, the rearrangement of the iV.O-ketene acetal, formed in situ by the reaction of A-propionyl-fra/w-(25,55)-dimethylpyrrolidine with ( )-crotyl alcohol, affords the [3,3]-rearrangement product in 50% yield and 10 1 diastereoselectivity (eq 9). 

Data are also shown for allene and ketene derivatives, which react similarly to alkenes in pericyclic reactions. The HOMO and LUMO energies are generally lower than those of ethene and the orbital coefficients of interest are those at C2 and C3 in the LUMO of allenes and Cl and C2 in ketenes. As will be seen in Sections 11.4.B and 11.11, the LUMO energies and coefficients are important for predicting reactivity and selectivity in several types of pericyclic reactions. 

The Meerwein-Eschenmoser-Claisen rearrangement is one of the most useful pericyclic reactions. In its basic form, it involves the conversion of an allylic alcohol 1 to a ketene N, 0-acetal 2, which undergoes rapid [3,3]-sigmatropic rearrangement to yield a y,d-unsaturated amide 3 (Scheme 7.1). In accordance with the general electronic effects observed in Claisen rearrangements, the presence of an electron-donating amino substituent on the ketene acetal intermediate substantially increases the rate of the pericydic step. 

The synthesis of trans-3-acyl- 3-lactam methyl esters 107 has been reported by Almqvist and coworkers [81, 82] by the Staudinger reaction of ketenes, generated from the Meldrum s acids 105, with methyl (i )-thiazoline-4-carboxylate 106 in benzene in the presence of hydrogen chloride (Scheme 3.36). An exceptionally low yield of 38% was obtained in the reaction of acetylketene. These esters could then be selectively reduced to the corresponding aldehydes 108 in moderate yields using diisobutylaluminum hydride (DIBAL-H). The Meldrum acids are well-known precursors of ketenes [83, 84]. They undergo a pericyclic reaction under thermal influence to generate ketenes with the release of carbon monoxide and acetone. 

Cycloaddition is a member of pericyclic reactions in which reactive components possessing conjugated jr-electrons (e.g., diene/dienophile, 1,3-dipole/dipolarophile, and ketene/imine) transform into cyclic molecules. These reactions proceed in a concerted mechanism with a high degree of regio- and stereoselectivity. Thus, they have been widely used for the construction of cyclic skeletons of numerous natural products and pharmacologically active molecules. Based on the jr-electron systems of reactants, they can be further classihed into [4 + 2], [3 + 2], and [2 + 2] cycloadditions that produce six-, five-, and four-membered rings, respectively. ... 

One group of anomalous reactions is that of ketenes with alkenes. These reactions appear to have some of the characteristics of pericyclic cycloadditions, such as being stereospecifically syn with respect to the double... 

On the other hand, stereospecificity is not always complete, and many ketene cycloadditions take place only when there is a strong donor substituent on the alkene. An ionic stepwise pathway by way of an intermediate zwitterion 3.34 is therefore entirely reasonable in accounting for many ketene cycloadditions. It seems likely that some of these reactions are pericyclic and some not, with the possibility of there,being a rather blurred borderline between the two mechanisms, with one bond forming so far ahead of the other that any symmetry in the orbitals is essentially lost. But when it is pericyclic, how does it overcome the symmetry-imposed barrier ... 

This is known as the linear approach, in which the carbene, with its two substituents already lined up where they will be in the product, comes straight down into the middle of the double bond. The two sulfur dioxide reactions above, 6.127 and 6.128, are also linear approaches, but these are both allowed, the former because the total number of electrons (6) is a (An I 2) number, and the latter because the triene is flexible enough to take up the role of antarafacial component. The alternative for a carbene is a nonlinear approach 6.130, in which the carbene approaches the double bond on its side, and then has the two substituents tilt upwards as the reaction proceeds, in order to arrive in their proper orientation in the product 6.131. The carbene is effectively able to take up the role of the antarafacial component as with ketenes, it is possible to connect up the orthogonal orbitals, as in 6.132 (dashed line), to make the nonlinear approach classifiably pericyclic and allowed. This avoids any problem there might be with reactions like 6.127 and 6.128 being pericyclic and the clearly related reaction 6.130—>6.131 seeming not to be. Similar considerations apply to the insertion of carbenes into cr bonds. 

There is experimental evidence for the nonlinear approach based on isotope effects,737 and calculations also support it, although they suggest that the reaction takes place in two steps by way of a short-lived diradical.738 Whatever the detailed mechanism, the carbene is effectively able to take up the role of the antarafacial component as with ketenes, it is possible to connect up the orthogonal orbitals, as in 6.163 (dashed line), to make the nonlinear approach classifiably pericyclic and allowed. This avoids any problem there might be with reactions like 6.158 and 6.159 being pericyclic and the clearly related reaction 6.161 > 6.162 seeming not to be. 

New types of combined pericycHc reactions 13UK228. Organocatalytic asymmetric cycloaddition reaction of ketenes 12CJ057. Pericyclic [4+2] and [3+2] cycloaddition reactions of nitroarenes in heterocyclic synthesis 13KGS102. 

The nickel-iminophosphine-catalysed 4- -2-cycloaddition of enones with allenes formed highly substituted dihydropyrans. The enantioselective amine-catalysed 4-I-2-cycloaddition of allenoates with oxo-dienes produced polysubstituted dihydropyrans in high yields and with high enantioselectivities. Novel enam-ine/metal Lewis acid bifunctional catalysis has been used in the asymmetric inverse-electron-demand hetero-Diels—Alder reactions of cyclic ketones with Q ,j9-unsaturated a-ketoesters. The 4- -2-cycloaddition of acylketenes (80) with 2-unsubstituted and 2-monosubstituted 3-aryl-2//-azirines (81) produced 1 1 (82) or 2 1 (83) adducts, being derivatives of 5-oxa-l-azabicyclo[4.1.0]hept-3-ene or 5,7-dioxa-l-azabicyclo[4.4.1]undeca-3,8-diene. The formation of the monoadducts proceeds via a stepwise non-pericyclic mechanism (Scheme 25). A-heterocyclic carbene-catalysed 4- -2-cycloaddition of ketenes with 1-azadienes yielded optically active 3,4-dihydropyrimidin-2-ones (93% ee) ... 

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