Cyclobutene opening stereochemistry

As a first example of an electrocyclic reaction illustrating stereochemistry, let us take the pair of conrotatory cyclobutene openings, showing that the reactions are stereospecific. 

Fig, 4,18 The stereochemistry of many reactions is easily predicted from the symmetry of molecular orbitals, usually the highest occupied n MO (n HOMO). In the ring closure of 1,3-butadiene to cyclobutene the phase (+ or —) of the HOMO (i//2) at the end carbons (the atoms that bond) is such that closure must occur in a conrotatory sense, giving a definite stereochemical outcome. In the example above there is only one product. The reverse process is actually thermodynamically favored, and the cis dimethyl cyclobutene opens to the cis, trans diene. No attempt is made here to show quantitatively the positions of the energy levels or to size the AOs according to their contributions to the MOs... 

From a synthetic point of view it is useful to know not only the direction of rotation of the substituents, i.e. the stereochemistry of the diene produced, but also the temperatures at which cyclobutenes open at synthetically useful rates. Much of the early work in this area has been done without the synthetic aspect in mind and some of the temperatures quoted below may be of value only for comparison purposes. 

Studies of the asymmetric photocycloadditions of the 1,3-dioxacyclohexenones (-)-20 or (-)-23, respectively with methyl cyclobutene opened a new route for the syntheses of enantiomerically pure (—)- and (-i-)-grandisol (19)81,82. This approach adopts the use of stereofacial differentiation by a rigid spirocyclic arrangement of the auxiliary and the enone. Since the alkene adds preferentially to face a of both enones, (— )-20 and (—)-23, Complementary enantiomeric product channels are available operating from a single enantiomer of the auxiliary in each case. The photocycloaddition reactions proceeded in a head-to-head fashion (HH/HT 7 1 at — 78 °C) to give tricyclic products with cis-anti-cts stereochemistry ( + )-21 and (+)-24, respectively. The auxiliary, ( —)-menthone, was smoothly removed by formic acid treatment of the cycloadduct (+)-21, no epimerization of the acetyl group in (— )-22 was observed under these mild conditions. 

There are several general classes of pericyclic reactions for which orbital symmetry factors determine both the stereochemistry and relative reactivity. The first class that we will consider are electrocyclic reactions. An electrocyclic reaction is defined as the formation of a single bond between the ends of a linear conjugated system of n electrons and the reverse process. An example is the thermal ring opening of cyclobutenes to butadienes ... 

Ring-opening of the frans-cyclobutene isomer shown takes place at much lower temperature than a similar ring-opening of the cis-cyclouiitciie isomer. Explain the temperature effect, and identify the stereochemistry of each reaction as either conrotatory or disrotatory. 

The stereochemistry of the cyclobutene isomerizations and the reverse processes of this type, involving the formation of a bond between the ends of a linear system containing a number of 7i--electrons, has been discussed by Woodward and Hoffmann (1965). They term such processes electrocyclic and consider that their steric course is determined by the symmetry of the highest occupied molecular orbital of the open-chain isomer. In an open-chain system containing 4 7T-electrons (such as butadiene), the symmetry of the highest occupied ground-state orbital is such that bonding interaction between the ends of the chain must involve overlap between orbital envelopes on opposite faces of the system, and this can only occur in a conrotatory process ... 

The stereochemistry of opening of cyclobutenes to butadienes was established some time before the advent of the pericyclic theory.88 It is conrotatory, in accord with the theory, as illustrated by the examples shown in Equations 12.46 and 12.47.89 Because the equilibrium in the monocyclic case favors the diene, the... 

The fact that the reactions take place in the direction of ring-opening is determined by thermodynamics, but the stereochemistry is most certainly not, for the cyclobutene 4.36 gives the thermodynamically more strained product 4.37 with one of the double bonds cis. Thermodynamics affects the stereochemistry only with the opening of the cyclobutene 4.38, which shows a preference for one of the conrotatory modes, that giving the trans,trans diene 4.39, where the rules could have led to the cis,cis diene equally well. This type of selectivity is called torqueoselectivity. 

This chiller is restricted to a short, but by no means complete, review of key synthetic routes to cyclobutenes, bmzocyclobutenes and cyclobutenones and a generally qualitative discussion of the way in which substituents control both the ease of ring opening and the stereochemistry of the products obtained. The reader should thus be in position to make useful predictions. Finally we have included pertinent synthetic applications which illustrate in useful and often very imaginative ways the value of the... 

In a lengthy theoretical paper, Rondan and Houk considered the available data, described ab initio calculations and discussed earlier explanations concerning the stereochemical aspects of the ring openings of substituted cyclobutenes.These authors came to the following conclusions. The stereochemistry of the thermal electrocyclic conrotatory ring opening of 3- and 4-substituted cyclobutenes is controlled by... 

The intermolecular version of this reaction results in the formation of complex systems with fewer rings. The group of Snapper has used this reaction in a number of routes to obtain complex natural products. Many of these processes involve the opening of cyclobutenes, and the bicyclic cyclobutenes (Eq. 6.30) provide excellent control of stereochemistry, with the products being highly strained so that they will undergo further thermal reactions [49]. 

The cyclobutene-butadiene interconversion involves four v electrons and is designated a process. Note that by the principle of microscopic reversibility, the number of tt electrons involved in the transformation is the same for ring opening as for ring closing. Once we know the number of tt electrons involved in an electrocyclic reaction and the method of activation, the stereochemistry of the process is fixed according to the rules outlined in Table 6.1. 

The cyclobutene ring first opens in an electrocyclic reaction 152. This must be conrotatory as it is a four electron process but there is no stereochemistry at this stage. Then an intramolecular Diels-Alder cycloaddition 153 closes the new six-membered ring. This is a particularly favourable reaction as the formation of the alkene completes a benzene ring. It would not be possible to prepare such an unstable diene so a tandem process is necessary. 

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