Course overview Instructor. Professor m-Christina White: whiteachemistrv. harvard. edu Mallinckrodt 314: office hrs. by appointment Teaching Fellows Qinghao Chen: chen @fas. harvard. edu Matthew Kanan: kanan @fas. harvard. edu Mark Taylor: mstavlor @fas. harvard. edu Course meeting Lectures: Tuesday and Thursday, 8: 30-10 AM Pfizer Lecture hall Sections: Alternate Wednesdays Mallinckrodt Rm. 318 Section 1: 1-2 30 PM Section 2: 2: 30-4 PM Section 3: 4-5 30 PM Introduction to transition metal-mediated organic chemistry. Organometallic mechanisms will be discussed in the context of homogeneous catalytic systems currently being used in organic synthesis(e.g. cross coupling, olefin metathesis, asymmetric hydrogenation, etc. ) Emphasis will be placed on developing an understanding of the properties of transition metal complexes and their interactions with organic substrates that promote chemical Course requirements: Exams: 20 pts(each) In class exams(three)will be given every 7-8 lectures. Although these exams will focus primarily on recent lecture topics, they will be cumu Exam I: October 10 Exam ll: November 12 Exam Ill: December Literature Discussions& Summaries: 20 pts Three papers from the recent literature will be distributed in class on alternating weeks and will be posted on the web. A one-page summary of one paper is due in section (JACS communication format recommended). All papers will be discussed in section and a familiarity with each is expected and may be tested for on exams. Literature summaries should clearly and succinctly convey the principal objective, results, and conclusions of the paper. A detailed, step-wise mechanism of the transition metal mediated reaction must be p roposed (preferably through figures)that describes the chemistry going on at the metal(d-electron count, complex electron count, oxidation state, ligand association/dissociation, etc)and at the organic substrate. Summaries submitted that exceed the l page limit will not be graded-no exceptions. No late summaries will be graded. Final Project: 20 pts well-characterized transition metal complex from the inorganic literature, propose its development into a viable catalytic system plication towards a 时1 process. NIH doctoral fellowship style recommended may not exceed all figures and ferences). Papers submitted that exceed the 4 page limit will not be graded-no exceptions. No late papers will be graded. Due January 15, 2003
Course Overview Instructor: Professor M.-Christina White: white@chemistry.harvard.edu Mallinckrodt 314: office hrs. by appointment Teaching Fellows: Qinghao Chen: qchen@fas.harvard.edu Matthew Kanan: kanan@fas.harvard.edu Mark Taylor: mstaylor@fas.harvard.edu Course Meeting: Lectures :Tuesday and Thursday, 8:30-10 AM Pfizer Lecture Hall Sections: Alternate Wednesdays Mallinckrodt Rm. 318 Begin September 25 Section 1: 1-2:30 PM Section 2: 2:30-4 PM Section 3: 4-5:30 PM Course Objective: Introduction to transition metal-mediated organic chemistry. Organometallic mechanisms will be discussed in the context of homogeneous catalytic systems currently being used in organic synthesis (e.g. cross coupling, olefin metathesis, asymmetric hydrogenation, etc.). Emphasis will be placed on developing an understanding of the properties of transition metal complexes and their interactions with organic substrates that promote chemical transformations. Course Requirements: Exams: 20 pts (each) In class exams (three) will be given every 7-8 lectures. Although these exams will focus primarily on recent lecture topics, they will be cumulative. Exam I: October 10 Exam II: November 12 Exam III: December 12 Literature Discussions & Summaries: 20 pts Three papers from the recent literature will be distributed in class on alternating weeks and will be posted on the web. A one-page summary of one paper is due in section (JACS communication format recommended). All papers will be discussed in section and a familiarity with each is expected and may be tested for on exams. Literature summaries should clearly and succinctly convey the principal objective, results, and conclusions of the paper. A detailed, step-wise mechanism of the transition metal mediated reaction must be p roposed (preferably through figures) that describes the chemistry going on at the metal (d-electron count, complex electron count, oxidation state, ligand association/dissociation, etc) and at the organic substrate. Summaries submitted that exceed the 1 page limit will not be graded- no exceptions. No late summaries will be graded. Final Project: 20 pts Starting with a well-characterized transition metal complex from the inorganic literature, propose its development into a viable catalytic system for application towards a synthetically useful process. NIH postdoctoral fellowship style recommended. Length may not exceed 4 pages (including all figures and references). Papers submitted that exceed the 4 page limit will not be graded- no exceptions. No late papers will be graded. Due January 15th, 2003
References of material in this are provided on the appropriate slides The following texts have been used as general reference guides in the preparation of these Crabtree, R.H. The Organometallic Chemistry of the Transition Metals; 3rd Edition Wiley: New York; 2001. (Available at the Harvard Coop) Huheey, J.E.; Keiter, E.A.; Keiter, R.L. Inorganic Chemistry: Principles of Structure and Reactivity; 4" Edition, Harper Collins: New York; 1993 Chemistry: 6 Edition, Wiley: New York: 1999 Collman, J. P; Hegedus, L S. Norton, J.R.; Finke, R.G. Principles and Applications of Organotransition Metal Chemistry, University Science: Mill Valley, CA; 1987 Hegedus, L.S. Transition Metals in the Synthesis of Complex Organic Molecules, Spessard, G.O.; Miessler, G L Organometallic Chemistry. Prentice Hall: Upper Saddle River. NJ Fleming, I. Frontier Orbitals and Organ ic Chemical Reactions. W iley: New York Corey, E.J. Cheng, X.-M. The Logic of Chemical Synthesis. Wiley: New York; 1989 Nicolaou, K.C.: Sorensen, EJ in Total Synthesis. VCH: Weinheim, Germany 1996 Non-Standard Journal abbreviations ACIEE Angewandte Chemie International Edition(English) HCa Helvetica Chimica Acta JACS Journal of the American Chemical Society Joc Journal of Organic Chemistry JOMC Journal of Organometallic Chemistry OL Organic Letters TL Tetrahedron letters
References The majority of material in this course is drawn from the primary literature. References are provided on the appropriate slides. The following texts have been used as general reference guides in the preparation of these lectures: · C rabtree, R.H. The Organometallic Chemistry of the Transition Metals; 3rd Edition; Wiley: New York; 2001. (Available at the Harvard Coop). · Huheey, J.E.; Keiter, E.A.; Keiter, R.L. Inorganic Chemistry: Principles of Structure and Reactivity; 4th Edition; HarperCollins: New York; 1993. · Co tton, F.A.; Wilkinson, G.; Murillo, C.A.; Bochmann, M. A dvanced Inorganic Chemistry; 6th Edition; Wiley: New York; 1999. · Collman, J.P.; Hegedus, L.S.; Norton, J.R.; Finke, R.G. Principles and Applications of Organotransition Metal Chemistry; University Science: Mill Valley, CA; 1987. · Hegedu s, L.S. Transition Metals in the Synthesis of Complex Organic Molecules; University Science: Mill Valley, CA; 1994. · Spessard, G.O.; Miessler, G.L. Organometallic Chemistry. Prentice Hall: Upper Saddle River, NJ; 1996. · Fleming, I. Frontier Orbitals and Organ ic Chemical Reactions. W iley: New York; 1976. · Corey, E.J.; Cheng, X.-M. The Logic of Chemical Synthesis. Wiley: New York; 1989. · Nicolaou, K.C.; Sorensen, E.J. Classics in Total Synthesis. VCH: Weinheim, Germany; 1996. Non-Standard Journal Abbreviations ACIEE Angewandte Chemie International Edition (English) HCA Helvetica Chimica Acta JACS Journal of the American Chemical Society JOC Journal of Organic Chemistry JOMC Journal of Organometallic Chemistry OL Organic Letters OM Organometallics TL Tetrahedron Letters
M C. White. Chem 153 Structure bonding-I Week of september 17. 2002 Organotransition Metal chemistry Organotransition Metal Chemistry(MCw definition): Transition metal mediated reactions that solve (or have potential to solve) challenging problems in the synthesis of organic molecules Coordination Chemistry Organometallic Chemistry The chemistry of transition metal complexes that have The chemistry of transition metal complexes that have noncarbon ligands(Werner complexes). Classification M-C bonds(organometallic complexes). Classification applies to the catalyst and all reaction intermediates applies to the catalyst and/or reaction intermediates R(O HCN NCCH3 HICCN Sharpless titanium-tartrate Trost enyne cycloisomerization catalyst epoxidation catalyst OTf NOH+-BuOOH 4A CH2Cl2,-20C CO,Me CO,Me 0 C(O) proposed intermediate oposed intermediate OH 70-90% yield CO,Me 94>98%ee Sharpless JACS 1987(109)5765 Trost JACS2002(124)5025 de lera synthesis 1995 285
M.C. White, Chem 153 Structure & Bonding -1- Week of September 17, 2002 Organotransition Metal Chemistry Organotransition Metal Chemistry (MCW definition): Transition metal mediated reactions that solve (or have potential to solve) challenging problems in the synthesis of organic molecules. Coordination Chemistry: The chemistry of transition metal complexes that have noncarbon ligands (Werner complexes). Classification applies to the catalyst and all reaction intermediates. Organometallic Chemistry: The chemistry of transition metal complexes that have M-C bonds (organometallic complexes). Classification applies to the catalyst and/or reaction intermediates. Ru H3CCN NCCH3 H3CCN (PF6-) R R Ru NCCH3 (PF6-) R Trost enyne cycloisomerization catalyst Trost JACS 2002 (124) 5025. + + proposed intermediate PPh3 Pd Ph3P PPh3 Ph3P Suzuki cross-coupling catalyst B(OH)2 N OTf CO2Me Ph3P Pd Ph3P N CO2Me proposed intermediate N CO2Me de Lera Synthesis 1995 285. O TiIV RO RO O TiIV O O O R'(O)C R' OR R' O OR OH t-BuOOH, 4Å MS O TiIV RO OR O TiIV O O R'(O)C CO2R O O R' O O t-Bu R R R OH O Sharpless JACS 1987 (109) 5765. Sharpless titanium-tartrate epoxidation catalyst CH2Cl2, -20oC 70-90% yield 94->98% ee proposed intermediate C(O)R' C(O)R
MC.White,Chem 153 Structure bonding-2 Week of September 17, 200 Complexity generating Reactions Wender's 5+2] Cycloadditions co C4H4CI2, 80 C, 3.5h OHH OH 90% Wender OL 2001(3)2105 Tandem heck Php Aco Ag,CO3, THF, reflux TBSO 82% OTBS Overman JOC 1993(58)5304
M.C. White, Chem 153 Structure & Bonding -2- Week of September 17, 2002 Complexity Generating Reactions OH O 1 3 10 12 O OH H OC Rh OC Cl Cl Rh CO CO 0.5 mol% C4H4Cl2, 80oC, 3.5h 90% 1 3 6 6 10 12 Wender's [5+2] Cycloadditions Wender OL 2001 (3) 2105. Tandem Heck O I O H TBSO O O H OTBS AcO Pd Ph3P OAc PPh3 10mol% Ag2CO3, THF, reflux 82% Overman JOC 1993 (58) 5304
MC.White,Chem 153 Structure bonding -3- Week of September 17, 200 Reactive Site Selectivity in Multifunctional Molecules No protecting groups used! The majority of the mass recovered after reaction termination was unreacted starting material OMe OMe PPh3 OMe Ru DH H O H PPh3 10 mol% CH] Ch, rt, 22h Meo 49% Meo E:z:1:1 HO HO Meo OMe OMe Schreiber JAcs1997(119)5106
M.C. White, Chem 153 Structure & Bonding -3- Week of September 17, 2002 Reactive Site Selectivity in Multifunctional Molecules HO MeO O OH N O H O O O OH OMe OMe O H HO MeO O OH N O H O O O OH OMe OMe O HO MeO O OH N O H O O O OH OMe OMe O H H H FK 506 Ru PPh3 PPh3 Cl Cl Ph H 10 mol% CH2Cl2, rt, 22h 49% E:Z ; 1:1 Schreiber JACS 1997 (119) 5106. No protecting groups used! The majority of the mass recovered after reaction termination was unreacted starting material