D A. Evans Introduction to carbenes Carbenoids-2 Chem 206 http:/www.courses.fasharvardedu/-chem206/ Useful References to the Carbene Literature Chemistry 206 Recent Review Article Chemistry of Diazocar McKervey et al. Chem Rev. 1994, 94, 1091 Advanced Organic Chemistry Books Modern Catalytic methods for Organic Synthesis with Diazo Compounds M. P. Doyle, Wiley, 1998 Lecture Number 35 Carbenes and Nitrenes in"Reactive molecules: The neutral reactive Intermediates in Organic Chemistry, Wentrup, C W. 1984, Wiley, p. 162 Introduction to Carbenes Carbenoids-2 Rearrangements of Carbenes and Nitrenes in Rearrangements in Ground Excited States, Academic Press, DeMayo ed, Jones, W. M. 1980, p. 95 a Thermally Induced Carbene Rearrangements Carbonyl Ylides and their reactions Carbene Chemistry, 2nd ed. Academic Press, Kirmse, W, 1971 R 0⑨ Oxonium Sulfonium Ylides and their reactions The Automerization of Naphthalene(The Cume Question from Helli) Rationaliz ○Q=0Q Reading Assignment for this Lecture: 13C-labeled C,ohg is isomerized into B-13C-labeled C1oh8 at 1035.C Carey Sundberg, Advanced Organic Chemistry, 4th Ed Part B Chapter 10, "Reactiona Involving Highly Reactive L.T.scot,JAcs1991,13,9692 Electron-Deficient Intermediates".263-350 Lecture 09A Simmons-Smith Reaction: Enantioselective variants Lecture 26B Synthetic Applications of a-Diazocarbonyl Compounds Provide a mechanism for this transformation Lecture 35A The Use of Fischer Carbenes in Organic Synthesis Lecture 35B The Synthetic Applications of Carbonyl Ylides 1000°c Corannulene 10% Matthew d shair Monday, December 16. 2002 Scott, L T, et aL., JACS 113 7082(1991)
D. A. Evans Chem 206 Matthew D. Shair Monday, December 16 , 2002 http://www.courses.fas.harvard.edu/~chem206/ Reading Assignment for this Lecture: Introduction to Carbenes & Carbenoids-2 Recent Review Article: Chemistry of Diazocarbonyls: McKervey et al. Chem Rev. 1994, 94, 1091. Carbenes and Nitrenes in "Reactive Molecules: The Neutral Reactive Intermediates in Organic Chemistry", Wentrup, C. W. 1984, Wiley, p. 162. Rearrangements of Carbenes and Nitrenes in Rearrangements in Ground & Excited States, Academic Press, DeMayo ed., Jones, W. M. 1980, p. 95. Carbene Chemistry, 2nd ed. Academic Press, Kirmse, W., 1971. Books: Modern Catalytic methods for Organic Synthesis with Diazo Compounds; M. P. Doyle, Wiley, 1998. Carey & Sundberg, Advanced Organic Chemistry, 4th Ed. Part B Chapter 10, "Reactiona Involving Highly Reactive Electron-Deficient Intermediates", 263-350 . Useful References to the Carbene Literature Lecture 09A Simmons-Smith Reaction: Enantioselective Variants Lecture 26B Synthetic Applications of a-Diazocarbonyl Compounds Lecture 35A The Use of Fischer Carbenes in Organic Synthesis Lecture 35B The Synthetic Applications of Carbonyl Ylides Chemistry 206 Advanced Organic Chemistry Lecture Number 35 Introduction to Carbenes & Carbenoids-2 ■ Thermally Induced Carbene Rearrangements ■ Carbonyl Ylides and their Reactions R C R R R O R O R R R R O R R R ■ Oxonium & Sulfonium Ylides and their Reactions R C R R X R R X R C R R •• •• The Automerization of Naphthalene (The Cume Question from Hell!) a– 13C-labeled C10H8 is isomerized into b– 13C-labeled C10H8 at 1035 °C D Rationalize Scott, L.T., et. al., JACS 113 7082 (1991) Corannulene 10% £ 10-4 Torr 1000° C Provide a Mechanism for this Transformation L. T. Scott, JACS 1991, 113, 9692
D A Evans. D. Guterman Thermal Generation of carbene Intermediates Chem 206 Carbenes are Accessible via Sigmatropic Rearrangement The Automerization of Naphthalene(The Cume Question from Hell!) [1, 2] Shifts: Alpha-Alkynone Cyclizations H72 1 C-labeled Canh, at1035°c Conditions: 620C. 12-16 Torr, Quartz filled quartz Tube i Mechanism-1: L. T Scott, JACS 1977. 99, 4506 2s+2a S M 3 18 +2a 12s+r2a 1378% a For the azulene-naphthalene Isomerization: AG=-30.7 kcal/mol(298K The Activation energy for the isomerization: AG =+86 kcal/mol 89% I Mechanism-2, 3: L. T. Scot, JACS 1991, 113, 969 90% rpf, M tion -3 Karpf, M, Dreiding, A s, He/v. Chim. Acta. 67 1963(1984) A(HB-HA)=-34 kcal/mol (MNDO)
D. A. Evans, D. Guterman Chem 206 Carbenes are Accessible via Sigmatropic Rearrangement O H O H H H O O O O O O O O O O O O O O Karpf, M., Dreiding, A.S., Helv. Chim. Acta. 67 1963 (1984) Clovene 80% (+ 19% isomers) 14 Torr N2 , 1 Hr 620° C Me Me O H H Me Me Me ■ [1,2] Shifts: Alpha-Alkynone Cyclizations Karpf, M., Dreiding, A., Helv. Chim. Acta. 65 13 (1982) Conditions: 620° C, 12-16 Torr, Quartz filled Quartz Tube [1,2] • • 90% 8 92 _ Recovery 54 46 _ 89% 78% 13 _ 87 80% 60 22 18 _ S.M. 3° 2° 1° The Automerization of Naphthalene (The Cume Question from Hell!) a– 13C-labeled C10H8 is isomerized into b– 13C-labeled C10H8 at 1035 °C D s 2s + s 2a p 2s + p 2a p 2s + p 2a s 2s + s 2a ■ For the azulene–naphthalene Isomerization: DG° = –30.7 kcal/mol (298K) ■ The Activation energy for the isomerization: DG ± = +86 kcal/mol H H ■ Mechanism-1: L. T. Scott, JACS 1977, 99, 4506; ■ Mechanism-2,3: L. T. Scott, JACS 1991, 113, 9692. H H •• H H H •• H H H •• H H H H X X B D(HB–HA) = –3.4 kcal/mol (MNDO) A BF BF B + A 900 °C 21%+ 79% Rationalize Thermal Generation of Carbene Intermediates Option–2 Option–3 O C-H insertion H D
D A Evans. D Guterman Thermal Generation of carbene intermediates Chem 206 Provide a mechanism for this transformation Carbenes: Reaction with Heteroatoms 1000°c ggested Readi Houk and Wu J. Org. Chem. 1991, 56, 5657 Padwa and Hombuckle Chem Rev. 1991. 91.263 Scott, L T, et aL., JACS 113 7082 (1991) Review articl Padwa and Krumpe Tetrahedron 1992, 48, 5385 Hoffman, R W. Angew. Chem. Int. Ed. Engl. 1979, 18, 563 cKervey et al. chem. Rev. 1994, 94, 1091 Ylide Formation by the Interaction of Carbenoids 仓 R⊙O、④ Internals External Ring: 14e Generally, the carbene precursor of choice is a diazoalkane or, more frequently. an a-diazocarbonyl reagent. These can be decomposed via thermolysis or 1000°c photolysis. However, the most common method involves catalytic amounts of transition metals, such as copper or rhodium Dipolar Cyclo -H insertio ROOR X-Y R
Thermal Generation of Carbene Intermediates Chem 206 Scott, L.T., et. al., JACS 113 7082 (1991) Corannulene 10% £ 10-4 Torr 1000° C Provide a Mechanism for this Transformation Internal Ring: 6 e – External Ring: 14 e – C C £ 10-4 Torr 1000° C H H H H •• •• C–H Insertion Carbenes: Reaction with Heteroatoms Suggested Reading Houk and Wu J. Org. Chem. 1991, 56, 5657. Review Articles Padwa and Hornbuckle Chem. Rev. 1991, 91, 263. Padwa and Krumpe Tetrahedron 1992, 48, 5385. Hoffman, R. W. Angew. Chem. Int. Ed. Engl. 1979, 18, 563. McKervey et al. Chem. Rev. 1994, 94, 1091. R R R R O R O R R R Generally, the carbene precursor of choice is a diazoalkane or, more frequently, an a-diazocarbonyl reagent. These can be decomposed via thermolysis or photolysis. However, the most common method involves catalytic amounts of transition metals, such as copper or rhodium. Ylide Formation by the Interaction of Carbeneoids with Carbonyl Lone Pairs •• R O R R R R O R R R X Y R O R R R X Y Dipolar Cycloaddition D. A. Evans, D. Guterman H H
D. A. Evans. D. Barnes Carbonyl Ylids: Dipolar Cycloaddition Chem 206 Tandem Intramolecular Cyclization-Intermolecular Cycloaddition Reactions of Diazoimides: [3+2] addition R 2(oac)4 e NEC-COEt 00o RCHO DMAD O2CH3 Et SiH/BF3 Et2O Dipolar-Dipolarophile Cycloadditions: HOMO-LUMO Energies Carbonyl Ylides have very small HOMO-LUMO Maier, M. E: Evertz, K. Tetrahedron Lett. 1988. 29, 1677-1680 ylide dipolarophile Therefore, either raising the dipolarophile HOMo (electron-donating substituents )or lowering the LUMo (electron-withdrawing)will accelerat 000 the reaction LUMO HOMO Padwa et. al. Tetrahedron lett. 1992, 33, 4731-4734
D. A. Evans, D. Barnes Carbonyl Ylids: Dipolar Cycloaddition Chem 206 O CHN2 O O O R R O NPh R O O O H H O CO2CH3 CO2CH3 R O O N CO2Et R O O O R N C CO2Et R O NPh H O O Tandem Intramolecular Cyclization–Intermolecular Cycloaddition O O HOMO LUMO Dipolar-Dipolarophile Cycloadditions: HOMO–LUMO Energies Carbonyl Ylides have very small HOMO-LUMO gaps Energy ylide dipolarophile Therefore, either raising the dipolarophile HOMO (electron-donating substituents) or lowering the LUMO (electron-withdrawing) will accelerate the reaction. Reactions of Diazoimides: [3+2] addition 74% Et3SiH / BF3 •Et2O CH2Cl2 68% Maier, M. E.; Evertz, K. Tetrahedron Lett. 1988, 29, 1677-1680. O N Bn O H CH3 N Me H Me OH H O Bn O N Me O O O Bn N2 O N Bn O COMe H Me Me PhCH3 , 110 °C O N Bn O COMe Padwa et. al. Tetrahedron Lett. 1992, 33, 4731-4734. "high yield" Rh2 (OAc)4 PhH, reflux N Me O O O N2 N O Me H H O O N O N Me O O N2 N N Me O O O H H H 88% Me Me O RCHO DMAD Rh2 (OAc)4 Rh2 (OAc)4 –N2
D. A. Evans. K. Beaver Carbonyl Ylids: Dipolar Cycloaddition-2 Chem 206 Dipolar Cycloadditions: Carbonyl Ylides Reactions of Diazoimides: [3+2] addition-[4+2]retroaddit AcoMe N2Rh2(OAc). hCH3110°C CO2Et OCO,Et Me-N=C=o Dauben, JOC 1993 7635 Tigilane Skeleton 一 R=H OBI MeO2C Meo.c Me R2=H M Z= COMe, COmE N2 OMe Maier, M. E, Schoffling, B. Chem. Ber. 1989, 122, 1081-1087. Padwa. JOC 1995 2704 Lysergic Acid Skeleton Meoh H,80°c 85% CO2 Me 8-9 Me MeO.c Me MoC MeOH N-CO,Me Padwa. JOC 1995 6258 IPadwa,A; Hertzog, D L;Chinn, RL.Tetrahedron Lett.1989,30,4077-4080
D. A. Evans, K. Beaver Chem 206 H H Dipolar Cycloadditions: Carbonyl Ylides O CO2Et N2 O H H H OAcMe Me H H O O CO2Et H AcO Me Me H H O CO2Et O Me Me AcO H Dauben, JOC 1993 7635 Tigilane Skeleton (86%) N N O OMe Me O N2 O Bz N Bz O N MeO2C OM Me N Bz N O MeO2C O Me H H Rh2 (pfb)4 N N O Et Me CO2Me O N N O Et Me CO2Me O O N O O CO2Me N2 Et N Me (95%) Padwa, JOC 1995 6258 Padwa, JOC 1995 2704 Lysergic Acid Skeleton Vindoline Skeleton (93%) N Z N2 O O R 2 R 2 R 1 Me N O O R 1 R 2 R 2 Me Z O N Me O Z R 1 R 2 R 2 O Z R 1 R 2 R 2 N Me O O O N2 N O CO2Me COCH3 MeO2C O MeO Padwa, A.; Hertzog, D. L.; Chinn, R. L. Tetrahedron Lett. 1989, 30, 4077-4080. 85% Rh2 (OAc)4 , PhH, 80 °C Maier, M. E.; Schöffling, B. Chem. Ber. 1989, 122, 1081-1087. Yields = 44-63% R 1 = H, OBn R 2 = H, Me Z = COMe, CO2Me Rh2 (OAc)4 PhCH3 , 110 °C – Me–N=C=O + – Reactions of Diazoimides: [3+2] addition – [4+2] retroaddition MeO2C CO2Me N O O Me O N O O Me O CO2Me MeO2C O CO2Me MeO2C OH Me N CO2Me Carbonyl Ylids: Dipolar Cycloaddition–2 O O Rh2 (OAc)4 Rh2 (OAc)4 MeOH H MeOH