Stereoselectivity of electrocyclic reactions

Houk, K. N., Spelhneyer, D. C., Jefford, C. W., Rimbault, C. G., Wang, Y., Miller, R. D. (1988). Electronic Control of the Stereoselectivities of Electrocyclic Reactions of Cyclobutenes against Incredible Steric Odds. Journal of Organic Chemistry, 53, 2125-2127. 

Dolbier Jr, W. R., H. Koroniak, et al. (1996). Electronic control of stereoselectivities of electrocyclic reactions of cyclobutenes a triumph of theory in the prediction of organic reactions. Acc. Chem. Res. 29,471. 

The MOVB theory of stereoselection of "real" radical electrocyclic reactions destroys the impasse which has been reached in the field of radical chemistry with regards to the stereoselectivity of radical reactions, in general. 

The three-fragment MOVB theory described and applied above to the case of the allyl cation electrocyclization can be easily applied to any electrocyclic ring closure of a closed shell system with the conclusion always being that the stereoselectivity of the reaction is dictated by the symmetry labels of the pi HOMO and pi LUMO of the core pi system in the following way ... 

The formation of j8-lactams from aliphatic acid chlorides and imines has been reviewed. The reaction is assumed to proceed through in situ formation of a ketene, followed by interaction with the imine to form a zwitterionic intermediate, which undergoes an electrocyclic conrotatory ring closure to give the jS-lactam ring (Scheme 8). The stereoselectivity of the reaction is sensitive to both the electronic and steric effects of the substituents on the ( )- or (Z)-imine, and the former manifest themselves in the electronic torquoselectivity that occurs during the conrotating cyclization of a zwitterionic intermediate [shown for ( )-imine in Scheme 8]. ... 

Thermal and photochemical electrocyclic reactions are particularly useful in the synthesis of alkaloids (W. Oppolzer, 1973,1978 B K. Wiesner, 1968). A high degree of regio- and stereoselectivity can be reached, if cyclic olefin or enamine components are used in ene reactions or photochemical [2 + 2]cycloadditions. 

How can we account for the stereoselectivity of thermal electrocyclic reactions Our problem is to understand why it is that concerted 4n electro-cyclic rearrangements are conrotatory, whereas the corresponding 4n + 2 processes are disrotatory. From what has been said previously, we can expect that the conrotatory processes are related to the Mobius molecular orbitals and the disrotatory processes are related to Hiickel molecular orbitals. Let us see why this is so. Consider the electrocyclic interconversion of a 1,3-diene and a cyclobutene. In this case, the Hiickel transition state one having an... 

Not all electrocyclic reactions are stereoselective. It turns out that none of the three of the possible interconversions between triplet cyclopropylidene and allene should show SS, according to an analysis given by Borden (1967). 

It is now well established that the Nazarov cyclization is a pericyclic reaction belonging to the class of electrocyclizations. As with all pericyclic reactions, mectuuiism and stereochemistry are inexorably coupled and any discussion of one feature must invoke the other. In this section the stereospecific aspects of the Nazarov cyclization are discussed, the stereoselective aspects of the reaction are dealt with individually in each of the following sections. 

Similarities between mass spectral and thermal fragmentations are particularly common in certain reaction types. Electrocyclic reactions, for example, are frequently similar in the two processes. The thermal process has in general a higher stereoselectivity (because of the higher aromaticity in even-electron systems). Retro-Diels-Alder reactions are typical examples for the similarity of the two processes. Internal displacement reactions may also be similar in the two processes, mainly in the case of internal radical displacements. The relationship between mass spectra and thermal fragmentation is complex, and it is useful to discuss it for separate classes of compounds. 

The stereoselective synthesis of (+)-trichodiene was accomplished by K.E. Harding and co-workers. The synthesis of this natural product posed a challenge, since it contains two adjacent quaternary stereocenters. For this reason, they chose a stereospecific electrocyclic reaction, the Nazarov cyclization, as the key ring-forming step to control the stereochemistry. The cyclization precursor was prepared by the Friedel-Crafts acylation of 1,4-dimethyl-1-cyclohexene with the appropriate acid chloride using SnCU as the catalyst. The Nazarov cyclization was not efficient under protic acid catalysis (e.g., TFA), but in the presence of excess boron trifluoride etherate high yield of the cyclized products was obtained. It is important to note that the mildness of the reaction conditions accounts for the fact that both of the products had an intact stereocenter at C2. Under harsher conditions, the formation of the C2-C3 enone was also observed. 

Fig. 8. Stereoselective synthesis of coronafacic acid (31) through retro Diels-Alder and electrocyclic reactions...

A new synthesis of ( )-crinan (43), a compound possessing the basic ring skeleton of the alkaloid crinine, using a stereoselective photocyclization reaction has been devised.28 The imine (39), readily prepared from 2-allylcyclohexanone and benzylamine, was acetylated with piperonyloyl chloride to give the AT-acylena-mine (40). Photolysis of (40) in methanol solution gave compound (41) (15% yield) whose structure and stereochemistry were established by spectral means and by consideration of the proposed electrocyclic nature of the reaction. 

The case of butadiene-cyclobutene interconversion, which one might expect to provide a straightforward example illustrating the stereoselectivity of photochemical electrocyclization, is actually quite complex, especially when substituted systems are involved. We first consider experimental outcomes from the photolysis of butadiene and substituted derivatives, as well as the reverse reaction, the photochemical ringopening reactions of cyclobutenes. We then examine the 1,3,5-hexatriene system in the same way. 

An electrocyclic reaction is an intramolecular reaction in which the rearrangement of tt electrons leads to a cyclic product that has one fewer tt bond than the reactant. An electrocyclic reaction is completely stereoselective—it preferentially forms one stereoisomer. For example, when (2 , 4Z,6 )-octatriene undergoes an electrocyclic reaction under thermal conditions, only the cis product is formed when (2 , 4 6Z)-octatriene undergoes an electrocyclic reaction under thermal conditions, only the trans product is formed. Recall that E means the high-priority groups are on opposite sides of the double bond, and Z means the high-priority groups are on the same side of the double bond (Section 3.5). 

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