Pericyclic reactions stereoselectivity

The orbital phase theory includes the importance of orbital symmetry in chanical reactions pointed out by Fukui [11] in 1964 and estabhshed by Woodward and Holiimann [12,13] in 1965 as the stereoselection rule of the pericyclic reactions via cyclic transition states, and the 4n + 2n electron rule for the aromaticity by Hueckel. The pericyclic reactions and the cyclic conjugated molecules have a conunon feature or cychc geometries at the transition states and at the equihbrium structures, respectively. 

Photochemistry offers the possibility of simple syntheses of some materials that would be very difficult to synthesize by other means. Stereoselective syntheses of four-membered rings are an excellent example of this (Scheme 7.3). As discussed previously, pericyclic reactions, such as... 

Chapter 6 looks at concerted pericyclic reactions, including the Diels-Alder reaction, 1,3-dipolar cycloaddition, [3,3]- and [2,3]-sigmatropic rearrangements, and thermal elimination reactions. The carbon-carbon bond-forming reactions are emphasized and the stereoselectivity of the reactions is discussed in detail. 

Diels-Alder reactions are found to be little influenced by the introduction of radicals (cf. p. 300), or by changes in the polarity of the solvent they are thus unlikely to involve either radical or ion pair intermediates. They are found to proceed stereoselectively SYN with respect both to the diene and to the dienophile, and are believed to take place via a concerted pathway in which bond-formation and bond-breaking occur more or less simultaneously, though not necessarily to the same extent, in the transition state. This cyclic transition state is a planar, aromatic type, with consequent stabilisation because of the cyclic overlap that can occur between the six p orbitals of the constituent diene and dienophile. Such pericyclic reactions are considered further below (p. 341). 

It has been established that the course of the sequential pericyclic reaction of cyclopentadienones with acyclic conjugated alkadienes depends on the reaction temperature, thermal treatment at low temperatures affording 3a,4,7,7a-tetrahydroinden-l-one derivatives by way of a Cope rearrangement (see Scheme 38). Roman et al have developed an efficient stereoselective synthesis of enantiomerically pure i-nitrotricyclo[5.2.2.0 ]undeca-3,8-dienes via a tandem consecutive asymmetric Diels-Alder-Cope rearrangement (see Scheme 39). Adducts... 

Pericyclic reactions are unimolecular, concerted, uncatalyzed transformations. They take place in a highly stereoselective manner governed by symmetry proper-ties of interacting orbitals. - Characteristic of all these rearrangements is that they are reversible and may be effected thermally or photochemically. The compounds in equilibrium are usually interconverted through a cyclic transition state,224 although biradical mechanisms may also be operative. A few characteristic examples of pericyclic rearrangements relevant to hydrocarbon isomerizations are presented here. 

The Diels-Alder reaction,1 e.g. 1 + 2, is one of the most important reactions in organic synthesis because it makes two C-C bonds in one step and because it is regio- and stereoselective. It is a pericyclic reaction between a conjugated diene 1 and an alkene 2 or 4 (the dienophile) conjugated with, usually, an electron-withdrawing group Z forming a cyclohexene 3 or 5. 

An example of a pericyclic reaction that illustrates the rather amazing stereoselectivity that these reactions often exhibit is provided by the thermal and photochemical interconversions of dienes and cyclobutenes. When (2A,4fi )-hcxadicnc is heated, it cyclizes to form /rans-3,4-dimethylcyclobutene. None of the cis-isomer is produced. In the reverse reaction the cyclobutene opens to produce only the ( , j-isomcr of the hexadiene. The reaction is completely stereospecific in both directions ... 

J. Jurczak, T. Bauer, C. Chapuis, D. Craig, M. Cinquini, F. Cozzi, W. Sander, P. Binger, D. Fox, B. B. Snider, J. Mattay, R. Conrads, H.-U. ReiBig, Formation of C-C Bonds by Pericyclic Reactions—Cycloadditions, in Methoden Org. Chem. (Houben-Weyl) 4th ed. 1952-, Stereoselective Synthesis (G. Helmchen, R. W. Hoffmann, J. Mulzer, E. Schaumann, Eds.), Vol. E21c, 2735, Georg Thieme Verlag, Stuttgart, 1995. 

This chapter is divided into two sections, largely separating stereospecific reactions from the merely stereoselective. The first deals with the ionic stereospecific reactions, and the explanations based on molecular orbital theory for the sense of the stereospecificity. The second deals with stereoselective reactions, in which a new stereocentre is created selectively under the influence of one or more existing stereochemical features, which is also sometimes a question of how the orbitals interact. The stereospecificity that is such a striking feature of pericyclic reactions is covered in the next chapter. 

Evanseck, J. D. Thomas IV, B. E. Spelhneyer, D. C. Houk, K. N. Transition structures of thermally allowed disrotatoiy electrocyclizations. The prediction of stereoselective substituent effects in six-electron pericyclic reactions, J. Org. Chem. 1995, 60,7134-7141. 

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. 

Tandem pericyclic reactions are a powerful strategy for construction of complex, polycyclic compounds. In recent years tandem [4 + 2]/[3 + 2] chemistry of nitro-alkenes and nitronates has been developed by Denmark et al. as a general approach to functionalized pyrrolidine-containing structures [118]. Within the subclass of inter [4 -I- 2]/intra [3 + 2] cycloadditions, they have documented the fused mode (/3-tether, Eq. 77), spiro mode (a-tether, Eq. 78), and bridged mode (a-tether, Eq. 79 or /3-tether, Eq. 80) constructions. These are highly stereoselective processes in the presence of Lewis acid such as SnCU and are amenable to asymmetric modification by use of chiral vinyl ethers. Finally, the nitroso acetals are readily transformed, by hydroge-nolysis, into polycyclic, a-hydroxypyrrolidinones, 4-aminocyclohexanones, and cyclo-pentylamines. 

The Diels-Alder reaction of a diene and a dienophile has become one of the most powerful carbon-carbon bond-forming processes [81]. In normal Diels-Alder reactions of an electron-poor dienophile with an electron-rich diene, the main interaction is between the HOMO of the diene and the LUMO of the dienophile. Coordination of a Lewis acid to the dienophile reduces its frontier orbital energies, and this increases the rate of the reaction. Regio- and stereoselectivity are also markedly affected by the Lewis acid. Recent extensive studies on the design of chiral Lewis acids have led to fruitful results in the control of the stereochemistry of a variety of pericyclic reactions. Several chirally modified Lewis acids have been developed for the asymmetric Diels-Alder reaction [82,83] and spectacular advances have recently been achieved in this area. Various kinds of polymer-supported chiral Lewis acid have also been developed. Polymer-supported A1 Lewis acids such as 62 have been used in the Diels-Alder reaction of cyclopentadiene and methacrolein (Eq. 20) [84] as has polymer-supported Ti alkoxide 63 [84]. These Ti catalysts are readily prepared and have high activity in the Diels-Alder reaction. 

The C,C-bond-forming reactions can be classified as polar reactions, in which an activated donor reacts selectively with an acceptor or vice versa radical reactions, which are increasingly applied in coupling or addition reactions because they do not interfere with polar groups in the molecule and thus save steps as no protections are needed [43] pericyclic reactions, especially cycloadditions, for the construction of ring compounds with high stereoselectivity [45] and transition metal-catalyzed reactions [46]. 

Altenbach used the Michael addition of sodium methyl malonate to allene (206) for a dia-stereoselective spiroannulation to a steroid (equation 72). Or, in imaginative work by Okamura, allenyl sulfoxides were transformed into enantiomerically pure hydrocarbons by pericyclic reactions like electrocyclic ring closure (equation 73) or intramolecular cycloaddition (equation 74). Note that the starting materials (propargylic alcohols) are readily accessible as single enantiomers. 

For each class of pericyclic reactions two or more of the following characteristics will be discussed the typical reactions, regioselectivity, stereoselectivity, and stereospecificity. The discussions of typical reactions and stereospecificity will help you recognize when pericyclic reactions are occurring in a particular chemical reaction. The discussions of regioselectivity, stereoselectivity, and stereospecificity will allow you to predict the structures and stereochemistry of the products obtained from pericyclic reactions. 

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... 

A commoner way to make heterocycles by pericyclic reactions is to use 1,3-dipolar cycloadditions. These often occur without catalysis and so are compatible with many other reactions. The starting material 182 for this asymmetric synthesis of swainsonine was derived from a natural sugar (chiral pool strategy, chapter 23). An exceptionally stereoselective Wittig reaction gave the Z-alkene 183 (chapter 15) and the alcohol was converted into the azide 184 with diphenylphos-phoryl azide.24... 

It is more difficult to explain the effect of substituents on the rates, and on the regio- and stereoselectivities of the unimolecular pericyclic reactions. We cannot strictly look at the HOMO and LUMO of each component, as we could with bimolecular reactions, and therefore cannot properly use frontier orbitals to explain the effects of electron-donating and electron-withdrawing substituents on the rates.905 The effects are profound, sometimes even strong enough to override the Woodward-Hoffmann rules.906... 

---