Chem 206D. A. Evans Matthew D. Shair Friday, December 20, 2002 http://www.courses.fas.harvard.edu/~chem206/ Reading Assignment for this Lecture: Introduction to Photochemistry Chemistry 206 Advanced Organic Chemistry Lecture Number 36 Introduction to Photochemistry a73 Introduction to Electronic Excitationa73 Franck-Condon Principle, Jabolonski Diagram a73 Photochemistry of Olefins and Dienesa73 Photochemistry of Carbonyl Compounds a73 Norrish Type-I & II Processesa73 Paterno-Büchi Reaction a73 [2 + 2] Photocycloaddition of Olefins Carey, and Sundberg, Advanced Organic Chemistry, Part A fourth Edition, Chepter 13, "Photochemistry", pp 743-789 "New insights into an old mechanism: [2 + 2] photocycloaddition of enones to alkenes.", Schuster, D. I.; Lem, G.; Kaprinidis, N. A. Chem. Rev. 1993, 93, 3. "Stereoselective intermolecular [2+2]-photocycloaddition reactions and their application in synthesis.", Bach, T. Synthesis 1998, 683-703. "[2+2] photocycloaddition/fragmentation strategies for the synthesis of natural and unnatural products.", Winkler, J. D.; Bowen, C. M.; Liotta, F. Chem. Rev. 1995, 95, 2003- 2020. "Synthetic Applications of Intramolecular Enone-Olefin Photocycloadditions.", Crimmins, M. T. Chem. Rev. 1988, 88, 1453. "The meta photocycloaddition of arenes to alkenes.", Cornelisse,Chem. Rev. 1993, 93, 615. Worthwhile General Reviews Chem 206, 1999 Final Exam Question. Provide a mechanism for the followingtransformation that explains the observed stereochemistry (Marshall, JOC, 1971, 214). HO Me hν PhH O Me "Stereoselective intermolecular [2+2]-photocycloaddition reactions and their application in synthesis.", Bach, T. Synthesis 1998, 683-703. (handout) "[2+2] photocycloaddition/fragmentation strategies for the synthesis of natural and unnatural products.", Winkler, J. D.; Bowen, C. M.; Liotta, F. Chem. Rev. 1995, 95, 2003-2020. (handout) O Me hν Me OMechanism?? NO2 O HN O R hν R–NH2 + CO2 NO CHO The above reaction forms the basis of a photo-labile protecting gtroup strategy for amines and alcohols Chem 206B. Breit, D. A. Evans Introduction to Photochemistry Background ReadingCarey, and Sundberg, Advanced Organic Chemistry, Parts A Third Edition, Chepter 13, "Photochemistry", pp 729-765 "New insights into an old mechanism: [2 + 2] photocycloaddition of enones to alkenes.", Schuster, D. I.; Lem, G.; Kaprinidis, N. A. Chem. Rev. 1993, 93, 3. "Stereoselective intermolecular [2+2]-photocycloaddition reactions and their application in synthesis.", Bach, T. Synthesis 1998, 683-703. "[2+2] photocycloaddition/fragmentation strategies for the synthesis of natural and unnatural products.", Winkler, J. D.; Bowen, C. M.; Liotta, F. Chem. Rev. 1995, 95, 2003- 2020."Synthetic Applications of Intramolecular Enone-Olefin Photocycloadditions.", Crimmins, M. T. Chem. Rev. 1988, 88, 1453."The meta photocycloaddition of arenes to alkenes.", Cornelisse, J. Chem. Rev. 1993, 93, 615. Worthwhile General Reviews 10-5–10-6 kcal/mol2-12 kcal/mol 40-140 kcal/molElectronic StatesFunctional Groups H & C ConnectivityNMRInfrared Ultraviolet-Visible Energy RangeInformationBasic Types a73 Important Regions of the Electromagnetic Spectrum Electrons are excited to higher energy levels when a molecule absorbsa photon of energy equal to the energy difference between the ground- state electronic level and the excited state electronic level. E = hν = h cλ a73 Light-induced electron excitation E (kcal/mol) = 2.86 x 10+4 Knowing the absorption wavelength in nm, you can calculate the the energy λ( in nm) for λ = 200 nm: E = 143 kcal for λ = 700 nm: E = 40.9 kcal for λ = 200 nm: E = 143 kcal for λ = 700 nm: E = 40.9 kcal ?E electronic σ? A–B σ A–B r 0 internuclear distance Consider a simple diatomic molecule A–B A B a73 Morse Curve Pote ntial Energ y r 0 (internuclear distance) E electronic ?E vibration excited state ground state a73 Franck-Condon Principle: Upon light-induced electronic excitation, only the electrons are reorganized; the heavier nuclei stay in their ground-state geometry. (Vertical Transitions) Time scale: electron excitation: 10-15 s Time scale: nuclei movement: 10-12 s B A Chem 206B. Breit, D. A. Evans Introduction to Photochemistry Summary of Photochemical Processes Energ y r 0 (internuclear distance) S0 S1 T1 Excitation(+ hν1) Fluorescence(– hν2) Intersystemcrossing Phosphorescence(– hν3) nonradiativedecay (–?) Substrates Absorption max (nm)190–200 220–250250–270 270–300270–280 310–330280–300 250–280 Simple alkenesAcyclic dienes Cyclioc dienesStyrenes Saturated ketonesUnsaturated ketones Aromatic ketones (aldehydes)Aromatic compounds Pyrex Glass 300 nmabsorbs Quartz Glass 200 nmabsorbs transmits transmits Hg lamp 254 nm, 313 nm, 366 nm M = 2S + 1 S = Σ s M: multiplicityS: total spin s: spin of a single electron (±1/2) S0 S1 or S2T 1 allowedforbiddenS 0 σ σ?pi pi* n pi* vacuum UV only (?E large) UV(VIS) allowedforbidden (Does not mean impossible. Implies only that probability for that particular transition is low.) Selection RulesNot all excitations/transitions are allowed (have high probability): (a) Spin-forbidden: Transitions between states of different multiplicity M (b) Space-forbidden: transitions between orbitals which do not overlap. a73 Sensitizer: e.g. acetophenone, benzophenone Small ?E between S0 & S1. Facile excitation into S1 followed by ISC into T1.Interaction with substrate: Substrate (S0) + Sens. (T1) Substrate (T1) + Sens. (S0) a73 Triplet-Quencher: e.g. O2, piperylene Me Reacts immediately with molecules in T1 excited state, depopulate T1 Quencher (S0) + Substrate (T1) Quencher (T1) + Substrate (S0) 400 nm 400 nm Spins Paired: Singlet State: S = Σ s = (+1/2 –1/2) = 0Spins Unpaired: Triplet State: S = Σ s = (+1/2 +1/2) = 1 Substrate reacts via S1 excited state. Substrate reacts via T1 excited state. Substrate reacts vi S1 excited state. Chem 206B. Breit, D. A. Evans Introduction to Photochemistry Jablonski Diagram Chem 206D. A. Evans Introduction to Photochemistry Photochemical Reactions Frontier MO Description Fleming, I. "Frontier Orbitals and Organic Chemical Reactions", Chapter 6, "Photochemical Reactions" Reactions of Olefins pi* pi concerted The [2 + 2] cycloaddition of two olefins exhibits the option of being concertedif one of the olefins reacts out of its photochemically excited state. a54 bonding bonding HOMO + energy a54 + light a54 pi pi* newHOMO light Consider [2 + 2] cycloaddition: Photochemical activation LUMO CC CC CC CC C C C C C C CC CC The rotatory motion of ring closure may be reversed by photo-activation controtation1e- Ψ4 (hexatriene HOMO)2e- 2e-1e- 2e-2e- 2e- light Hexatriene: disrotation Ψ3 (hexatriene HOMO) HMe H Me H Me H Me Me H H MeMe HMe H Ψ4 Excited State Geometry pi* pipi pi* newHOMO light CRH R H Excited state (1S and 3T) Rotation Me Me RO R H Me Me RO R heat disrotation light controtation Me Me RO R H One of the first cases where heat and light induced electrocyclizations followed different pathways. Havinga, Tetrahedron, 1961, 16, 146. Me Me RO R H Me Me RO R H Ψ4 Ψ1 Ψ3 Ψ3 Ψ1 Chem 206B. Breit, D. A. Evans Introduction to Photochemistry Hmm2 = – 33 kcal/moltrans-cyclohexene cis-cyclohexene Me Me MeMe OO hν benzenet-BuOH MeCH 2 MeMe OO 85% yield Evans et. al. unpublished results, 1972 HO Me hν PhH O Me (Marshall, JOC, 1971, 214). Cis–Trans Isomerization Cis & trans olefins may be interconverted by either direct or sensitized irradiation CRH R HCR H C HR hνsensitizer 3 CHR C HR sensitizer: benzene (0S)benzene hν (1S)-benzene (3T)-benzene(0S)-olefin (0S)-benzene(3T)-olefin Me hν sensitizer Me (trans-cyclohexene) Me H Me H ORSensitized Photohydration CH2 HReview: Marshall, Accounts Chem. Res 1969, 2, 33 Ground state trans cyclohexene is now sufficiently basic to deprotonate alcohols Me H Me H OR CH2 H Product Partitioning Me Me Me MeMe Me Me Me Me hνsensitizer HOH tBuOH 28% 72% 70% 30% Kropp, JACS 1966, 88, 4091Marshall, JACS 1966, 88, 4092 Me Me Me hν xylenet-BuOH/H2O Me CH2Me50% Marshall Me Me Me Me MeMe –H+ ROH ROH RO Chem 206B. Breit, D. A. Evans Introduction to Photochemistry Excited State Geometry of Dienes CCH C HRC HRH light CH R HCC HRH Allylmethylene diradical CCH C RHC HHR light cis-cis CCH C HRC HHR cis-trans CCH C HRC HRH trans-transnot observed Explain why trans-trans isomer is not observed in this photosiomerization CH Me HCC HHH CCH C HMeC HHH light Me Me H Me H direct H2C Me Ph Ph hυ PhPhsensitized hυ directPhPh Rationalize the course of the sensitized transformation O H H hν Photochemistry of Carbonyl Compounds Photochemical excitation of carbonyl group: n → pi* * planar pyramidal dipole: 2.34D dipole: 1.56D pi* pi n groundstate n - pi*singlet n - pi*triplet pi - pi*singlet pi - pi*triplet Note the diradical character of the excited states. Photochemicallyexcited carbonyl compounds undergo many of the reactions typical of radical species. n → pi* S1 T1 C O HH 80–85 kcal/mol 75–80 kcal/mol C O C O Chem 206B. Breit, D. A. Evans Introduction to Photochemistry Norrish-type I reactions ( -cleavage) O R R' hνn → pi* O R R' * occurs from bothS1 and T1 O R + R' Regioselectivity of bond cleavage: Depends on relative stability of the two radicals formed. O Barton, JACS 1985, 107, 3607. Ph hν O Ph Hhere: benzyl vs. phenyl radical O Ph Ph hν Ph Ph - CO Quinkert, TL 1963, 1863. C/O and C/N bond cleavage: Photo–Fries rearrangement O O R hν OH O R OH R O + 1 : 1 O O R phenoxy radical(resonance stabilized) solvent cage O O R O O R Reaction occurs readily if stabilized radicals are formed. Ph H O Σ products(decarbonylation, recombination, disproportionation) NPh O hν N OH NH O N O Chem. Ber. 1969, 342. Norrish-type II reactions Photo-excitation of carbonyl is followed by hydrogen atom abstraction. Acc. Chem. Res. 1971, 4, 168. Intermolecular (Reaction with solvent) Ar O R hν O Ar R * S-H OH Ar R * + S Dim. OHOH Ar ArR R OHOH Ar RR ArPinacol-type productsIntramolecular (a) Photoenolization CH2R O Ph C O Ph H CHROH Ph CHR OD Ph CHR O Ph hν * H-Abstr. D C/N bond cleavage: Aza–Fries rearrangement HR Chem 206B. Breit, D. A. Evans Introduction to Photochemistry Norrish-type II reactions continued...gamma H Abstraction"Femptosecond Dynamics of Norrish Type-II Reaction: Nonconcerted Hydrogen Transfer and Diradical Intermediiacy", Zewail et. al., Angew. Chemie, Int. Ed. 2000, 39, 260 Me O Me OH +76 +37 MeOH +26OHMe lifetime: 900 ns a73 Rxn may take place out of either singlet or triplet statea73 Fragmentation to enol is favored entropically a73 The decomposition of the diradical is essentially barrierlessa73 Fragmentation to enol is favored entropically a73 Fagmentation similar to McLafferty Rearrangement in mass spectroscopy Me Me O barrier+88 Remote hydrogen abstraction O Me H Me H R O CH2 O hν O Me H Me R O CH2 OH H(D) O Me H Me R O CH2 OH H(D) Breslow, Acc. Chem. Res. 1980, 13, 170. H H H hν Paterno-Büchi Reaction Photochemical [2+2] cycloaddition of ketones/aldehydes with olefins: The general reaction: O R + hν O R + * aliphatic via S1 aromatic via T1 O R triplet orsinglet diradical general: via most stable diradical. O R Oxetane With some aliphatic aldehydes stereospecific reactions have been observed: O Me *S1 O O Me Me Me Me H Me H Me O Mevia singlet- diradical bond formationfaster than rotation! Me Me JACS 1991, 93, 1277; TL 1964, 1425; JACS 1968, 90, 6863; JACS 1972, 94, 8761. Aromatic aldehydes/ketones show stereo-convergent behavior: T. Bach, Liebigs Ann. 1997, 1627.(a) simple diastereoselectivity R2 R1 OTMS R1 OTMS R2 O Ph *T1+ O Ph *T1+ Ar O R1 OTMS R2 life time long enoughto undergo bond rotation O R2 OTMSR1Ph T1 ISC to S1 recomb. thermodyn.most stable product formedAr HH R2R1 OOTMS(Main product also for R2 = H) dr > 9:1 Reviews: Scharf, ACIEE 1991, 30, 477; Ynoue, Chem. Rev. 1992, 92, 741. H H H H CH2 Chem 206B. Breit, D. A. Evans Introduction to Photochemistry Induced facial diastereoselectivity R1 OTMS Me RL* PhCHOhν O OTMSR1Ph RL MeH up to 95:5(rel. config. atC1–/C3) controls rel. config. 1 3 H OTMSR1 Me RL OArH A1,3 minimizedBach et al. Application in natural product synthesis O Me Me O OBn+ hν O Me O Me H OBn head to head, exo (±) Asteltoxin Schreiber, JACS 1984, 106, 4186;Science 1985, 857; JACS, 1983, 105, 660. Transannular reaction OAcO AcO O Mehν Paterno-Büchi Reaction conbtinued.... H "Stereoselective intermolecular [2+2]-photocycloaddition reactions and their application in synthesis.", Bach, T. Synthesis 1998, 683-703. Photocycloaddition of Enones "New insights into an old mechanism: [2 + 2] photocycloaddition of enones to alkenes.", Schuster, D. I.; Lem, G.; Kaprinidis, N. A. Chem. Rev. 1993, 93, 3. "[2+2] photocycloaddition/fragmentation strategies for the synthesis of natural and unnatural products.", Winkler, J. D.; Bowen, C. M.; Liotta, F. Chem. Rev. 1995, 95, 2003-2020. "Synthetic Applications of Intramolecular Enone-Olefin Photocycloadditions.", Crimmins, M. T. Chem. Rev. 1988, 88, 1453. Reaction Regiochemistry O hνR O R ++ head-to-head (HH) Favored: R = EWG HN O Me Me R hν R = CNR = OEt HN O Me Me R HN O Me Me R 82 : 1805 : 95 O Rhead-to-tail (HT) Favored: R = Donor Ring Fusion Stereochemistry O OMe hν MeO O OMeOMe H H49% + O OMeOMe H H21% + 6% other products Corey JACS 1964, 86, 485 It is hard to rationalize the trans ring fusionstereochemistry through the intervention of a 1,4-diradical Chem 206B. Breit, D. A. Evans Introduction to Photochemistry Photocycloaddition of Enones continued..... O OO hν O O O hν O n–pi* a70 These diradicals, formed in approximately equal amounts, partition to products and reactants Products Identifiable Intermediates H O H O hν a70 T1H2C C CH2 H O 96%a73 Intramolecular reactions work nicely O Me Me Me hν O Me Heathcock, JOC 1985, 50, 4135. CH3O CH3 Me hν CH3 CH3 CH3O Oppolzer, JACS 1978, 100, 2583. Me Me Photochemical Rearrangement of 4,4-Dialkyl-Substituted Cyclohexenones Review: Schuster in "Rearrangements in Ground and Excited States", Vol. 3, de Mayo (Ed.), Academic Press, NY 1980, Chapter 17. The reaction: O R R 2 34 4 3 2 O R R a73 Reaction is stereospecifica73 can be described as a concerted [pi2 aσ2a] CA O R1 R2 H HR2R1 O a73 for R1, R2 = Aryl non-concerted mechanisms compete Inversionof Configuration O H3C n-Pr O Me n-PrExample hν hν Cyclohexadienone Rearrangement Zimmerman, ACIEE 1969, 8, 1; Acc. Chem. Res. 1978, 11, 65; de Mayo, Chapter 18. O Ph Ph hν PhPh O O T1 Ph Ph O Ph Ph O Ph Ph O Ph Ph Chem 206D. A. Evans, T. B. Dunn [2+2] Photocycloaddiltion: Synthetic Applications H (±)-Epiprecapnelladiene Pattenden, G., et al. J. Chem. Soc., Chem. Comm. 1980, 1195.Pattenden, G., et al. J. Chem. Soc., Perkin Trans. I 1983, 1913. OMe OMe O OBz Me Three steps 56% OMe OBz H hν, Pyrexhexane, rt, 6 h98% 1) LiHMDS, MeI2) KOH, DMSO MeH H MeMe O O 36% Me H MeMe Me Six steps 28% Stereochemical rationale (Pattenden) O OBz H Me H O OBz H Me Irradiation of the enol acetate resulted in a 92:8 mixture, presumably due to the smaller size of the acetate versus benzoate. One diastereomer Epiprecapnelladiene (+)-Longifolene and (+)-Sativene Oppolzer, W., et al. J. Am. Chem. Soc. 1978, 100, 2583.Oppolzer, W., et al. Helv. Chim. Acta. 1984, 67, 1154. 3 steps 77% O O OBnOCOOH H hν, Pyrex,cyclohexane, rt, 2 h 3:2 epimeric mixture at starred carbon 95% ee H2, Pd/CAcOH 96% O OCO2Bn O OCO2Bn H HO H O H H Me Me Me Me MeMe(+)-Longifolene (+)-Sativene Six steps47% Ten steps 18% 85% ee H * Chem 206D. A. Evans, T. B. Dunn [2+2] Photocycloaddiltion: Synthetic Applications H (±)-Pentalenene, (±)-Pentalenic Acid & (±)-Deoxypentalenic Acid from a Common Precursor COOEt O Me Me COOMe Me O MeMe Me COOMeCOOEt H hν, uranium glasshexane, rt, 36 h 73% 9 Me O CO2R Me Me COOEt H Me O CO2R Me Me COOEt HH Consistent with predominant stereochemistry at C-9 Stereochemical rationale (Crimmins) Crimmins, M.T., et al. J. Org. Chem. 1984, 49, 2076.Crimmins, M.T., et al. J. Am. Chem. Soc. 1986, 108, 800. C-9 drMe Eti-Pr 13:117:1>20:1 O MeMe Me COOMeCOOEt H 9 + COOMe COOMeMe Me 3 steps44% Varying the size of the indicated alkyl group influenced the stereoselectivity major (93%) minor (7%) R=H, R'=Me, Pentalenene, nine steps, 27% R=OH, R'=COOH, Pentalenic acid, eight steps, 42% R=H, R'=COOH, Deoxypentalenic acid, eleven steps, 22% R MeMe Me H R' H StepsMe Me OH COOMe COOEt Me Li, NH3, THF90% Crimmins, M.T. et al. J. Am. Chem. Soc. 1999, 121, 10249.Crimmins, M.T. et al. Tetrahedron Lett. 1989, 30, 5997. (±)-Ginkgolide B 8 steps OO COOEt TESO OO TESO COOEthν, uranium glasshexane, rt, 18 h 100%t-Bu O EtOOC t-Bu OO t-Bu O O 4 steps49% OO t-Bu O O OH OMe OMe O O O O OO O t-Bu H OHHOH MeHO dimethyldioxirane 2) MeOH, TsOH, 89% 1) H2O, TsOH CH(OMe)3 12 steps11% Ginkgolide B One isomer 71% R