The Woodward-Hoffmann Rules and the Conservation of Orbital Symmetry

Transcription

1 h242b cott Virgil The Woodward-offmann ules and the onservation of rbital ymmetry The Woodward-offmann rules encompass the realm of pericyclic reactions: electrocyclizations cycloadditions sigmatropic rearrangements ene reactions Pericyclic reactions are prevalent in synthetic organic chemistry as well as in biosynthetic processes. This can be seen in the case of the endiandric acids, biosynthetically synthesized by Nicolaou: 3 endiandric acid 3 Nicolaou, K.. J. m. hem. oc. 1982, 104, 5555; J. m. hem. oc. 1982, 104, 5557; J. m. hem. oc. 1982, 104, 5558; J. m. hem. oc. 1982, 104, The principle of conservation of orbital symmetry applies NL to concerted pericyclic reactions. In these cases it serves as a powerful predictive tool. Electrocyclic eactions Woodward,..; offmann,. J. m. hem. oc. 1965, 87(2), "We define as electrocyclic transformations the formation of a single bond between the termini of a linear system containing k π- electrons and the converse process." "In such changes, fixed geometrical isomerism imposed upon the open-chain system is related to rigid tetrahedral isomerism in the cyclic array. priori, this relationship might be disrotatory or conrotatory." NTT ITT

2 Electrocyclic eactions of 1,3-utadiene: utadiene Molecular rbitals Under Thermal onditions Thermal yclization of utadiene LUM M NTT "Thus, in an ope an open chai open chain system chain syste the symmetry of of the highest the highest occupie highes is such th that a bondi a bonding inte bonding interaction be involve overlap between orbial envelopes on opposite faces of the sy system, andthis can only only be achie be achieved conrotatory process." utadiene Molecular rbitals Under otochemical onditions otochemical yclization of utadiene LUM M ITT "n the oth promotion of an electr an electron to excited state leads t leads to a reversal to a reversal of the t relationships in the orbitals the orbitals mainly orbitals redistribution, with t the conseq consequence that a sys undergoes a thermally thermally induced dis induced d transformation in the ground sta the ground state shou conrotatory course when photochemically excited, and vice versa." nalogous analyses of larger π-systems will allow determination of the stereochemical course of electrocyclic ring closings and openings under thermal and photochemical conditions.

3 Thermal and otochemical yclizations of 1,3,5-exatrienes: ITT Thermal M "onversely, in open systems containing 4n + 2 π-electrons, terminal bonding interaction within ground-state molecules requires overlap of orbital envelopes on the same face of the system, attainable only by disrotatory displacements." NTT otochemical M ased on these these observat observations for electrocyc for electrocyclic reactions of electrocyclic react electrocyclic reactions can be summarized in terms of the number of electron pairs involved in the cyclization or ring opening: Number of electron pairs hν dd Even isrotatory onrotatory onrotatory isrotatory dd-electron systems follow same stereochemical course as the even system containing one further electron. harged systems should behave in the same manner as neutral systems containing the same number of electrons. owever, there are a few caveats that deserve mention! "It should be emphasized that our hypothesis specifies in any case which of two types of geometrical displacements will represent a favored process, but does not exclude the operation of the other under very energetic conditions." onrotatory (Thermally llowed) isrotatory (Thermally "isallowed") onrotatory (Thermally llowed) isrotatory (Thermally "isallowed") onrotatory (Thermally llowed) isrotatory (Thermally "isallowed") When these traditionally "disallowed" processes are observed they are usually occurring by non-concerted pathways, such as diradical pathways.

4 Torquoselectivity in Electrocyclic eactions: In the ca case of cyc of cyclobutene cyclobutene electrocyclic electrocyclic ring opening, you may have processes that give different isomeric products. The principle of torquoselectivity guides us in deciding which conrotatory process will be favored for a given electrocyclic ring opening T T Examination of the two pos the two possible t two possible transitio possible transition states for tra negative steric interaction in transition state that is not seen in transition state. Thus, only product is observed. The preference of transition state over transition state is called torquoselectivity. For the ele electrocyclic ring op ring opening of the [4.2.0 opening of the [4.2.0] fused bicyc of the [4. the cyclooctatriene with two trans olefins () will be highly disfavored compared to the cyclooctatriene containing only cis olefins (). Electrocyclic eactions in Nature and ynthetic hemistry: The Endiandric cids 2 2 endiandric acid 8π Thermal onrotatory Electrocyclization [4+2] Thermal ycloaddition (iels-lder) 2 6π Thermal isrotatory Electrocyclization 2 endiandric acid F Nicolaou, K.. J. m. hem. oc. 1982, 104, 5555; J. m. hem. oc. 1982, 104, 5557; J. m. hem. oc. 1982, 104, 5558; J. m. hem. oc. 1982, 104, 5560.

5 ycloaddition eactions offmann,.; Woodward,.. J. m. hem. oc. 1965, 87(9), Whereas electrocyclic reactions involve the net intramolecular interconversion of one σ-bond and one π-bond, cycloaddition reactions consist of the net intermolecular conversion of k π-bonds to k σ-bonds to form a cyclic product. m n m-2 n-2 m and n are numbers of π-electrons in each component The [4 + 2] ycloaddition: iene ienophile ψ 3 M LUM disrotatory cycloaddition In the thermal [4 + 2] cycloaddition reaction, mixing occurs between the highest occupied molecular orbital (M) on the diene component and the lowest unoccupied molecular orbital (LUM) on the dienophile component. The formation of two new σ-bonds (at the expense of two π-bonds) requires disrotatory movement of the frontier molecular orbitals.

6 tereospecificity of the Thermal [4 + 2] ycloaddition: The thermal [4 + 2] electrocyclizaton is selectively disrotatory, allowing absolute elucidation of the product cycle's stereochemistry. Thus, this is a sterespecific transformation: The [2 + 2] ycloaddition Thermally, the [2 + 2] cycloaddition is geometrically forbidden, as the M and LUM of the participating olefins would not be able to achieve the orbital overlap required for σ-bond formation. LUM M n the other hand, the photochemical [2 + 2] cycloaddition is allowed and leads to stereospecific cyclobutane formation. hν M LUM

7 The Thermal [2 + 2] ycloaddition: loser Look Previously, it was said that the thermal [2 + 2] cycloaddition was geometrically forbidden, not orbital symmetry forbidden. To understand this, two new concepts, suprafaciality and antarafaciality, must be introduced. The consequence of suprafaciality and antarafaciality is that many processes that are Woodward-offmann allowed can be forbidden to occur because of geometrical constraints on the system. uprafaciality- when, in a pericyclic reaction, the bondforming interaction occurs on the same face of a π-system, as in thermal [4 + 2]. ntarafaciality- when, in a pericyclic reaction, the bondforming interactions occur on opposite faces of a π-system. ethylene [2 + 2] ketene [2 + 2] symmetry allowed, geometrically forbidden symmetry allowed, geometrically allowed Why does the thermal [2 + 2] fail with two alkenes but succeed with ketene? emoval of steric bulk (-atoms) around the π-system (as in the ketene) allows antarafacial bond formation that is geometrically forbidden in the ethylene [2 + 2]. ased on these observations for cycloaddition reactions of π-systems, the Woodward-offmann rules for cycloaddition reactions can be summarized in terms of the number of electron pairs involved in the cyclizations: Number of Electron Pairs even (4n) odd (4n + 2) otochemical suprafacial-suprafacial suprafacial-antarafacial Thermal suprafacial-antarafacial suprafacial-suprafacial In the suprafacial-suprafacial cases, the cycloadditions are symmetry allowed and geometrically allowed. In the suprafacial-antarafacial cases, the cycloadditions are symmetry allowed and generally geometrically disallowed. Type of ycloaddition Thermal otochemical 2-component 3-component 4-component bove are some examples of known concerted cycloaddition reactions. While reactions involving more than 4 components are allowed by orbital symmetry they must overcome entropic barriers. For this reason, multicomponent systems with more than 4 π-systems have not been observed.

8 risis of Nomenclature Traditional convention has it that cycloadditions are named [m + n] to denote the number of atoms in each component. Woodward and offmann altered this so that m and n refer to the number of electrons in each component. This does not impact neutral species, but has consequences with dipolar species. N ' 1,3 dipolar cycloaddition N ' Traditionally: [3 + 2] W- alteration: [4 + 2] ome common cycloadditions: 1,3 dipolar cycloadditions Example: zonolysis ' ' ' ' suprafacial with respect to both components formal [4 + 2] ycloaddition heletropic eactions ' ' suprafacial [4 + 2] 2 - lass of retrocycloadditions when one atom is extruded from a cyclic π-system antarafacial [6 + 2] 2 - emonstrative of antarafacial vs. suprafacial selectivity because geometrical constraints are overcome in constrained cyclic systems. arbene addition to olefins ' ' ' ' - arbenes have two orbitals interacting on one carbon in cycloadditions: M occupied by 2 e - is sp 3 orbital and interacts with olefin LUM LUM is vacant p-orbital and interacts with olefin M LUM M M LUM - This dual overlap is why carbenes have a side-on approach instead of head-on [14 + 2] cycloaddition N N N N N N N N

9 Inverse emand iels-lder ycloaddition: In a normal electron demand iels-lder, the M of the electron rich diene reacts with the LUM of the electron deficient dienophile. The inverse demand Iels-lder occurs between the LUM of an electron poor diene and the M of an electron rich dienophile. iene ienophile ψ 3 LUM M tereoselectivity of ycloadditions: The Endo/Exo Problem + minor major M econdary rbital verlap favors endo transition state; strong enough to override sterics endo T LUM M exo T LUM Exo product is thermodynamic, therefore lower in energy egioselectivity and ubstituent Effects Examination of orbital coefficients allows prediction of the regioselectivity of [4 + 2] cycloadditions. oefficients of similar size should be matched to give maximal overlap in σ-bond formation. EG EG EG M EG LUM EG EG EG EG EG EG EG EG The orbital coefficient effect of a substituent at the 1 position of a diene outweighs that of a substituent at the 2 position of the diene. For a thorough treatment of orbital coefficients in cycloadditions: Fleming, I. Frontier rbitals and rganic hemical eactions, h ; Wiley-V: Weinheim.

10 igmatropic earrangements Woodward,..; offmann,. J. J. m. hem. oc. 1965, 8(11), "We define as a sigmatropic change of order [i, j] the migration of a σ-bond, flanked by one or more π-electron systems, to a new position whose termini are i - 1 and j - 1 atoms removed from the original bonded loci, in an uncatalyzed intramolecular process." 1 2 k j 1 sigmatropic change of order [1, j] 2 k j "In the first process, here designated suprafacial, the hydrogen atom is associated at all times with the same face of the π- system, and the transition state possesses a plane of symmetry, σ. In the second, antarafacial process, the migrating atom is passed from the top face of one carbon terminus to the bottom of the other, through a transition state characterized by a twofold axis of symmetry 2." [1, j] suprafacial sigmatropic reaction [1, j] antarafacial sigmatropic reaction igmatropic earrangements of ydrogen: [1,2] cationic suprafacial-suprafacial rearrangement The cationic [1,2] shift of a hydrogen atom is suprafacial with respect to both components in the system. It is important to note that migrating hydrogen atoms can only behave in a suprafacial manner due to the symmetry of a 1s orbital. π- systems, however, can behave in either a suprafacial or an antarafacial manner, owing to the plane of symmetry present in p orbitals.

11 [1,3] antarafacial-suprafacial rearrangement Thermal earrangement Geometrically isallowed! In the thermal case, [1,3] hydrogen shifts require one component to be antarafacial. ince the migrating hydrogen atom must be suprafacial, the π-system would be antarafacial. Geometrical constraints on the system, however, prohibit this process since the bond overlap achieved in the transition state would be inadequate for bond formation. otochemically, this process requires two suprafacial components. This eliminates the geometrical constraints of having an antarafacial component and allows the [1,3] hydrogen atom shift to occur. hν otochemical earrangement [1,5] suprafacial-suprafacial rearrangement Thermal earrangement The [1,5] thermal rearrangement of hydrogen requires that both components are suprafacial. Therefore, it is geometrically allowed. [1, j] thermal sigmatropic shifts in rings ymmetry and Geometrically llowed ymmetry llowed UT Geometrically Forbidden! [1, j] shifts of hydrogen atoms within rings is geometrically allowed only if both componts react suprafacially. This is seen in the case of a [1,5] hydrogen shift in cyclopentadienes (top figure). If, however, one component reacts antarafacially, the rearrangement will be geometrically forbidden, as the migrating hydrogen atom would have to travel through a - bond on its path to the opposite face of the π-system. This is observed in the case of a [1,7] hydrogen shift in cycloheptatrienes (bottom figure). [1, 7] hydrogen shifts in acyclic heptatrienes are observed because the length of the π-system permits the geometrical constraints seen in the [1,3] thermal shift situation to be overcome.

12 Thermal igmatropic earrangements of lkyl Groups: [1,3] antarafacial-suprafacial rearrangement [1,3] antara-supra ymmetry and Geometrically llowed! Inversion of tereochemistry Indicates ntarafacial earrangement Unlike a hydrogen atom, a migrating alkyl group can behave antarafacially. Thus, in a [1,3] antarafacial-suprafacial thermal rearrangement, the alkyl group is geometrically able to migrate on the same face of the π-system. The key is to recognize that the absolute configuration at the migrating alkyl group has inverted. This inversion of stereochemistry is the consequence of antarafacial migration by the alkyl group. [1,5] suprafacial-suprafacial rearrangements [1,5] supra-supra etention of tereochemistry Indicates uprafacial earrangement When alkyl groups migrate in an entirely suprafacial manner, the net stereochemical outcome is retention of absolute configuration at the migrating alkyl group. [1,7] antarafacial-suprafacial rearrangements [1,7] antara-supra Inversion of tereochemistry bserved [1,7] antarafacial-suprafacial thermal rearrangements are similar to their [1,3] counterparts and occur with inversion of the absolute configuration of the migrating alkyl group. The π-system is the suprafacial component. ased on these observations for sigmatropic rearrangements of of π-systems, the Woodward-offmann rules for sigmatropic rearrangements can be summarized in terms of the number of electron pairs involved in the rearrangements: Number of electron pairs hν dd Even supra-supra supra-antara supra-antara supra-supra

13 igmatropic earrangements in the iosynthesis of Natural Products: igmatropic earrangement of ipinnatin J: 3 hν [1,3] supra-supra etention of tereochemistry 3 bipinnatin J igmatropic earrangement of Precalciferol: 3 3 kallolide 3 3 [1,7] supra-antara thermal rearrangement precalciferol Vitamin [3,3] igmatropic earrangements: The laisen and ope earrangements ope earrangement laisen earrangement ope, laisen, and variants are all predicted to be [3,3] supra-supra thermal sigmatropic rearrangements chair transition state When possible, the [3,3] sigmatropic rearrangements prefer to proceed through chair transition states. tereochemistry is able to be translated through the transition state to the products. boat transition state ivinylcyclobutanes and divinylcyclopropanes prefer to rearrange through boat transition states from their cis conformations. Trans divinylcyclobutanes and divinylcyclopropanes will isomerize through diradical intermediates to their cis isomers and then undergo [3,3] sigmatropic rearrangements.

14 [2,3] igmatropic earrangements Mislow-Evans earrangement: [2,3] supra-supra thermal rearrangement mp M [2,3] TE (+)-pyrenolide Transition state: Engstrom, K. M.; ndoza, M..; Navarro-Villalobos, M.; Gin,.. ngew. hem., Int. Ed. 2001, 40, [2,3] Wittig earrangement T T T n-uli, TF T Li [2,3] TM TM T T TM First example of an asymmetric [2,3] Wittig rearrangement T T tork's prostoglandin intermediate 5 11 prostoglandins Transition state for rearrangement: Formation of 3 contiguous chiral centers to give a single stereoisomer! TM T T Nakazawa, M.; akamoto,.; Takahashi, T.; Tomooka, K.; Ishikawa, K.; Nakai, T. Tetrahedron Lett. 1993, 34,

15 Ene eactions 6 electron process suprafacial to all components involving: arbonyl Ene - 4 electron component, the ene (typically allylic) - 2 electron component, the enophile (π-bond) onia Ene N N N N N N talla-ene Mgl etero-ene e etro-ene lmg e The Woodward-offmann ules for Pericyclic eactions Number of Electron Pairs Number of ntarafacial omponents hν dd Even ero dd dd ero ne final example: Total ynthesis of olumbiasin Use the Woodward-offman rules to explain the stereochemical outcomes of the pericyclic reactions used in the olumbiasin syntheses by K.. Nicolaou and.. arrowven. chelotropic [4+2] [4+2] cycloaddition Nicolaou, K.. ngew. hem. Int. Ed. 2001, 113, t-u 4π-electrocyclic ring opening 6π-electroncyclic ring closing tautomerization t-u ( )-columbiasin arrowven,.. ngew. hem. Int. Ed. 2005, 117,