I. Basic Principles I-K. Pericyclic Reactionsccc.chem.pitt.edu/.../PericyclicReactions_HO.pdf ·...
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1 I-K. Pericyclic Reactions I. Basic Principles Nicolaou, K. C. et al. J. Am. Chem. Soc. 1982, 104, 5560. (Endiandric acids) Categories of Pericyclic Reactions • among the reactants and products usually at least one molecule is unsaturated • the reactions involve the formation or scission of σ-bonds and the consumption or generation of π-bonds • the electronic reorganization occurs in some sort of cyclic array of the participating atomic centers. Dr. P. Wipf Chem 2320 2/20/2007
Transcript of I. Basic Principles I-K. Pericyclic Reactionsccc.chem.pitt.edu/.../PericyclicReactions_HO.pdf ·...
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I-K. Pericyclic Reactions
I. Basic Principles
Nicolaou, K. C. et al. J. Am. Chem. Soc. 1982, 104, 5560. (Endiandric acids)
Categories of Pericyclic Reactions
• among the reactants and products usually at least one moleculeis unsaturated
• the reactions involve the formation or scission of σ-bonds andthe consumption or generation of π-bonds
• the electronic reorganization occurs in some sort of cyclic arrayof the participating atomic centers.
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Pericyclic 6-el. Processes:
Pericyclic reactions are apparently concerted: the electronic rearrangements involved inbond-making/bond-breaking proceed simultaneously in a one-step (one TS‡) process.
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Woodward-Hoffmann RulesAmong the theories that are commonly used to analyze pericyclicreactions, three are generally considered to be the most useful:
1. Fukui’s Frontier MO interactions. This analysis applies HOMO-LUMO interactions as well as orbitals close to HOMO & LUMO,and it is more intuitive that the original orbital symmetryarguments.
- Coulson, C. A.; Longuet-Higgins, H. C. Proc. Roy. Soc.A 1947, 192, 16.- Klopman & Salem (JACS 1968, 90, 223, 543, 553).- Fukui, K. Acc. Chem. Res. 1971, 4, 57.
Rather than considering the relative phases, i.e. symmetry, of allorbitals involved during the transformation of reactants intoproducts, the frontier orbital approach makes predictions for theoutcome of pericyclic reactions based on the highest occupiedmolecular orbital (HOMO) and the lowest unoccupied molecularorbital (LUMO). In this, the electrons in the HOMO of one reactantare looked upon as analogous to the outer (valence) electrons ofan atom, and reaction is then envisaged as involving the overlap ofthis (HOMO) orbital with the LUMO of the other reactant. Where,as in electrocyclic reactions, only one species is involved only theHOMO needs be considered.
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If, upon examination of the interactions that occur in the frontierorbitals (HOMO, LUMO if applicable, otherwise only HOMO) theinteractions are constructive (of the same phase, the reaction isconsidered “allowed”.If the orbital overlap is destructive (i.e. of different phase), then thereaction is “forbidden”.
Berson, J. A.; Nelson, G. L. J. Am.Chem. Soc. 1967, 89, 5303:
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2. The Dewar-Zimmerman Theory of AromaticTransition States.
This analysis is possibly the most general and easiest to apply to a broad range ofpericyclic reactions, but it is also the least anchored in fundamental physicalprinciples.
For applying this model, choose a basis set of 2p atomic orbitals for all atomsinvolved (1s for hydrogens).After assigning any phases to these orbitals (no relationship to MO’s is required!),connect the orbitals that interact in the starting materials, before the reactionbegins. Allow the reaction to proceed according to the postulated geometry;connect the lobes that begin to interact and were not connected in the startingmaterials.Count the number of phase inversions that occur - a phase inversion within anorbital is not counted.Based on the number of phase inversion of the orbital perimeter, identify thetopology of the system:Odd # of phase inversions: Möbius topologyEven # of phase inversions: Hückel topology
The transition state can now be assigned as antiaromatic or aromatic,based on the number of electrons in the system:Möbius topology: Aromatic for 4n, Antiaromatic for 4n+2Hückel topology: Aromatic for 4n+2, Antiaromatic for 4nif the transition state is aromatic, then the reaction is thermally allowed.If the transition state is antiaromatic, a photochemical process isrequired.
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3. The Woodward-Hoffmann Theory. This was the firsttheory to explain and predict the outcome of many pericyclicreactions. Therefore, it brought order and understanding tomany thermal and photochemical reactions. However, itused correlation diagrams, which are difficult and time-consuming to apply.
For thermally allowed reactions, the occupied orbitals of thestarting materials must correlate with occupied orbitals of theproduct. Correlation of orbitals is determined in terms ofsymmetry relationships.
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- [2,3] Sigmatropic rearrangement of sulfoniumylids:
- [1,2] Sigmatropic rearrangement of sulfoniumylids:
- [2,3] Sigmatropic rearrangement of allylic sulfoxides to allyl sulfenates (Mislow-Evansrearrangement):
- Wipf, P.; Lim, S. Chimia 1996, 50,157.
- [1,2] Sigmatropic rearrangement of quaternary ammonium salts to tertiary amines(Stevens rearrangement):
- [2,3] Sigmatropic rearrangement of quaternary benzylic ammonium salts to tertiary amines (Sommelet-Hauser rearrangement):
- [1,2] Sigmatropic rearrangement of tertiary amine oxides to substituted hydroxylamines (Meisenheimerrearrangement):
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CopeRearrangements
Thermal rearrangement of 1,5-dienes to isomeric 1,5-dienes:
Specific value for modern organic synthesis:
- Parent Cope involves no requirement for acid or base catalysis and can thus accommodate a widevariety of functional groups.- One of the most powerful methods of synthesis of medium rings.- Due to the highly ordered cyclic TS, the reaction is extremely stereospecific. Two unsymmetrical doublebonds and two asymmetric centers are translated to four new elements of stereochemistry, usually withnear quantitative symmetric transmission.The development of the oxy-Cope and anionic oxy-Cope reactions has greatly extended the utility of theCope rearrangement by allowing easier access to diene substrates, lowering the temperature required forrearrangement, and producing carbonyl substrates irreversibly.
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- Davies, H. M. L.; Calvo, R.; Ahmed, G. Tetrahedron Lett. 1997, 38, 1737. Type II(Roush, W. R. In Comprehensive Organic Synthesis; B. M. Trost and I. Fleming, Eds.;Pergamon Press: Oxford, 1991; Vol. 5; pp 513) cycloannulations betweenvinylcarbenoids and furans result in the rapid construction of fused [4.3.1.]-bicyclicsystems.
Claisen Rearrangements
- Wipf, P. In ComprehensiveOrganic Synthesis; B. M. Trost, I.Fleming and L. A. Paquette, Ed.;Pergamon: Oxford, 1991; Vol. 5; pp827-874.
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The Aromatic ClaisenRearrangement
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The Ireland Silyl Ester Enolate Rearrangement
Several factors contribute to the versatility of the ester enolate Claisenrearrangement.Among these are the ability to use a stoichiometric combination of the alcohol andthe acid components, the relatively low temperature of the pericyclic process thatallows for the assembly of complex, highly functionalized structures, and thetransformation of a carbon-oxygen into a carbon-carbon bond that lends itselfeasily to the assembly of contiguous quaternary centers.
Another particularly important aspect of the Ireland rearrangement is that, throughan efficient control of ketene acetal geometry, a highly reliable and predictabletransfer of stereochemistry from starting material to product can be realizedDeprotonation of crotyl ester with LDA in THF leads, via the selective formation ofthe kinetically favored (Z)-ester enolate, upon silylation to the (E)-silyl keteneacetal. After rearrangement at 65°C and mild hydrolysis of the silyl ester, a 87 : 13ratio of g,d-unsaturated acids is isolated in 79% yield. These two products can beobtained in a 19 : 81 ratio by using 23%HMPA/THF as a solvent system for thegeneration of the thermodynamically favored (Z)-silyl ketene acetal via thecorresponding (E)-lithium enolate. Wipf, P., "Claisen rearrangements." In B. M. Trost, I. Fleming and L. A. Paquette, editors.Comprehensive organic synthesis. Vol 5. Oxford: Pergamon; 1991. p. 827-874.
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Ireland, R. E.; Wipf, P.; Xiang, J.-N. J. Org. Chem. 1991, 56, 3572:
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Diels-Alder Reactions
Reviews:Nicolaou, K. C.; Snyder, S. A.; Montagnon, T.; Vassilikogiannakis,G. "The Diels-Alder reaction in total synthesis." Angew. Chem. Int.Ed. 2002, 41, 1668-1698.Corey, E. J. "Catalytic enantioselective Diels-Alder reactions:Methods, mechanistic fundamentals, pathways, and applications."Angew. Chem. Int. Ed. 2002, 41, 1650-1667.
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Intermolecular Diels-Alder Reactions
Woodward, R. B. et al. J. Am. Chem. Soc. 1952, 74, 4223.
Corey, E. J.; Weinshenker, N. M.; Schaaf, T. K.; Huber, W. J. Am. Chem. Soc. 1969, 91, 5675. With ketene equivalent.
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Boger, D. L.; Soenen, D. R.; Boyce, C. W.; Hedrick, M. P.; Jin, Q., "Total synthesis of ningalin B utilizing aheterocyclic azadiene Diels-Alder reaction and discovery of a new class of potent multidrug resistant (MDR)reversal agents." J. Org. Chem. 2000, 65, 2479-2483.
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Intramolecular Diels-Alder Reactions
Classification:-Roush, W. R. In Comprehensive Organic Synthesis; B. M. Trost and I. Fleming, Eds.; Pergamon Press: Oxford, 1991; Vol. 5;pp 513.
-Type I reactions involve trienes with the connecting chain attached to the diene terminus, while type IIsubstrates have the dienophile tethered via one of the internal diene positions.
Except for some specialized cases, type I IMDA are feasible only of the connecting chainscontain three or more atoms. In the vast majority of cases, the fused rather than the bridgedproduct is obtained, even when (Z)-dienes are used. Bridged product formation for type Idienes was only detected with connecting chains of 10 or more atoms. Type II dienes withbridging chains of three or four members cyclize exclusively to the syn-cycloadducts, since thetransition state for the anti-isomer is more strained. Type II cycloadditions are restricted tosubstrates with at least three bridging atoms owing to the strain that develops in the transitionstate.
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Uenishi, J.; Kawahama, R.; Yonemitsu, O. J. Org. Chem. 1997, 62, 1691.
Nicolaou, K. C. et al. J. Am. Chem. Soc. 1982, 104, 5560. (BiomimeticSynthesis of Endiandric acids)
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Danishefsky, S.; Morris, J.; Clizbe, L. A. J. Am. Chem. Soc. 1981, 103, 1602-4. Synthesis of pretyrosine(arogenate). Starting material: glutamate
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Asymmetric Diels-Alder
Corey, E. J.; Ensley, H. E. J. Am. Chem. Soc. 1975, 97, 6908.
Chiral Lewis Acid Catalysis
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Corey, E. J.; Loh, T. P.; Roper, T. D.; Azimioara, M. D.; Noe, M. C. J. Am. Chem. Soc. 1992, 111, 5493.
Evans, D. A.; Shaughnessy, E. A.; Barnes, D. M. Tetrahedron Lett. 1997, 38, 3193.
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Hetero-Diels Alder Reaction
Danishefsky, S. J. et al. Angew. Chem. Int. Ed. Engl. 1996, 35, 2801. Synthesis of epothilone A.
Jacobi, P. A.; Lee, K., "Total synthesis of stemoamide." J. Am. Chem. Soc. 1997, 119, 3409. An oxazoleDiels-Alder cycloaddition leads to the natural product in seven steps:
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Abe, H.; Aoyagi, S.; Kibayashi, C., "First total synthesis of the marine alkaloids (±)-fasicularin and (±)-lepadiformine based on stereocontrolled intramolecular acylnitroso-Diels-Alder reaction." J. Am. Chem. Soc.2000, 122, 4583-4592.
Homo-rDA Reactions
Liao, Y.; White, J. B. Tetrahedron Lett. 1990, 21, 5129. Orbital symmetry has to be considered for theexplanation of the course of these reactions. The thermally much more stable cis-isomer gives cyclohexenonepresumably via a stepwise process.
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Farina, V.; Reeves, J. T.; Senanayake, C. H.; Song, J. J., "Asymmetricsynthesis of active pharmaceutical ingredients." Chem. Rev. 2006, 106,2734-2793.
Tandem Isomerization-Diels-Alder-Retro-Diels-Alder
Rao, A. V. R.; Reddy, D. R. "A simple methodology for the synthesis of 3,4-dihydroisocoumarins." Synthetic Communications 1986, 16, 97-102.
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