Pericyclic reactions ketone

The thermo- and photocycloaddition of alkenes will be discussed in Chapter 12, on pericyclic reactions. On the other hand, transition-metals have effectively catalyzed some synthetically useful cycloaddition reactions in water. For example, Lubineau and co-worker reported a [4 + 3] cycloaddition by reacting a,a-dibromo ketones with furan or cyclopen-tadiene mediated by iron or copper, or a-chloro ketones in the presence of triethylamine (Eq. 3.48).185... 

Usually, the formation of a new chiral centre involves the conversion of a prochiral sp carbon atom into one with sp hybridisation, the methods most generally used being the aldol and related condensations, pericyclic reactions (especially the Diels-Alder reaction), epoxidation, cyclopropanation and additions to double bonds (hydrogenation and hydroboration). Another possibility is the conversion of a prochiral sp carbon atom into a chiral centre, as for instance in the a-substitution (alkylation, halogenation, etc.) of a ketone. 

Danheiser et al. developed a new aromatic annotation methodology for the total s)mthesis of hyellazole (245) by irradiation of the heteroaryl a-diazo ketone 675 in the presence of 1-methoxypropyne (590). This reaction proceeds via the photochemical Wolff rearrangement of the heteroaryl a-diazo ketone 675 to generate a vinylketene, followed by a cascade of three pericyclic reactions. 

In addition to participating in [2 + l]-cycloaddition reactions, divalent reactive intermediates can form ylides in the presence of carbonyl or other Lewis basic functionalities.108 These ylides participate in cycloaddition or other pericyclic reactions to furnish products with dramatically increased complexity. While carbenes (or metal carbenoids) are well known to participate in these pericyclic reactions, silylenes, in contrast, were reported to react with aldehydes or ketones to form cyclic siloxanes109,110 or enoxysilanes.111,112 Reaction of silylene with an a,p-unsaturated ester was known to produce an oxasilacyclopentene.109,113,114 By forming a silver silylenoid reactive intermediate, Woerpel and coworkers enabled involvement of divalent silylenes in pericyclic reactions involving silacarbonyl ylides115 to afford synthetically useful products.82,116,117... 

This section covers the formation of cyclopropanes via cyclization of reactive allylic intermediates (cations, anions, radicals). Included are those transformations of allylic functional derivatives (e.g. allylic halides, alcohols, aldehydes, ketones, acids, esters, boronates, Grignard reagents) to cyclopropyl derivatives that do not actually proceed via allylic reactive intermediates, but which are not covered by other sections of this volume. Additionally, this section will cover methods for the formation of cyclopropanes by pericyclic reactions. 

The power of pericyclic reactions for forming new carbon-carbon bonds is nicely illustrated by the use of the Claisen orthoester rearrangement to prepare y-ketoesters with a quaternary centre next to the ketone (Scheme 9)The use of silver salts to catalyse the acetylenic oxy- Cope rearrangement for the preparation of a,0-6,e-unsaturated ketones has also been reported [equation (10)].57... 

In 1984, Schreiber published a synthesis of the pheromone in which the majority of steps involve pericyclic reactions. Make sure you understand each one as it appears—re-read the appropriate part of Chapter 34 or this chapter if you have any problems. The first step is a photochemical [2 + 2] cycloaddition. You could not have predicted the regiochemistry, but it is typical of the cycloaddition of allenes with unsaturated ketones. 

For the protic acid catalyzed reaction, the cyclization commences with protonation of the divinyl ketone 9 and formation of a pentadienyl cation 10. An analogous process is operational in the case of Lewis acid-catalyzed reactions. The pentadienyl cation 10 then undergoes a 47t electrocyclic closure to give a cyclopentenylic cation 11. This cyclization is a pericyclic reaction and is governed by the rules for conservation of orbital symmetry. Namely, this means the cyclization occurs stereospecifically in a conrotatory fashion, with predictable relative configurations of the substituents (i.e., the R groups in 11 are anti). Elimination of a proton, followed by tautomerization gives product 13. ... 

Figure 15.18 shows several examples of electrocyclic processes. Since the reactions are always allowed in either a conrotatory or disrotatory manner, the key issue is the control of stereochemistry. Electrocyclic reactions provide a good example of the power of pericyclic reactions in this regard. In all cases, the reaction proceeds as predicted from the various theoretical approaches. The restrictions placed by the orbital analysis on the reaction pathway are nicely demonstrated by examples D and E in Figure 15.18 only the stereochemistry given is found. An instructive example of the fact that it is the number of electrons that controls the process, not the number of atoms or orbitals, is the conrotatory ring closure of the four-electron pentadienyl cation prepared by protonation of a divinyl ketone (example G). 

This process is very similar to the process we discussed for 1,3-dicarboxyhc acids. In the first step, a pericyclic reaction forms an enol, which then undergoes tautomerization to form a ketone. Decarboxylation can occur because the carboxyhc acid exhibits a carbonyl group in the (3 position, which enables the pericyclic reaction shown above. Below is an example of an acetoacetic ester synthesis. 

The transition state for the concerted reaction would be a six-electron Hiickel-type transition state. Such a process should not take place photo-chemically since only antiaromatic pericyclic reactions occur in this way. The reaction moreover seems to involve a triplet excited state since it occurs only in the presence of a ketone as sensitizer. Therefore there seems little doubt that it is, as indicated in equation (6.39), a G j-type process in which the first step is cleavage of a bond py to the excited diene system to give a pair of mesomeric biradicals. These combine on the ground-state surface to form the product. 

A closely related reaction has been performed with other aldehydes and even with ketones without a catalyst, but with heat. The aldehydes and ketones here are active ones, such as chloral and acetoacetic ester. The product in these cases is a 3-hydroxy alkene, and the mechanism is pericyclic ... 

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