carolyn l. ladd literature meeting april 9, 2014

Carolyn L. LaddLiterature Meeting

April 9, 2014

Do, H.-Q.; Bachman, S.; Bissember, A. C.; Peters, J. C.; Fu, G. C. J. Am. Chem. Soc. 2014, 136, 2162–2167.

Author ProfilesAuthor ProfilesAuthor ProfilesAuthor Profiles

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•B.S, MIT, 1985 (with Barry K. Sharpless)B.S, MIT, 1985 (with Barry K. Sharpless)•Ph.D, Harvard, 1991 (with David A. Evans)Ph.D, Harvard, 1991 (with David A. Evans)•PDF, Caltech, 1993 (with Robert H. Grubbs)PDF, Caltech, 1993 (with Robert H. Grubbs)

•Assistant Professor, MIT, 1993-1998Assistant Professor, MIT, 1993-1998•Associate Professor, MIT, 1998-1999Associate Professor, MIT, 1998-1999•Professor, MIT, 1999-2007Professor, MIT, 1999-2007•Fermenich Professor of Chemistry, MIT, 2007-Fermenich Professor of Chemistry, MIT, 2007-

20122012•Altair Professor of Chemistry, Caltech 2012-Altair Professor of Chemistry, Caltech 2012-

presentpresent

•B.S, University of Chicago, 1993 (with Gregory Hillhouse )B.S, University of Chicago, 1993 (with Gregory Hillhouse )•Marshall Scholar, University of Nottingham, (with James J. Marshall Scholar, University of Nottingham, (with James J.

Turner)Turner)•Ph.D, MIT , 1998 (with Christopher C. Cummins)Ph.D, MIT , 1998 (with Christopher C. Cummins)•PDF, Berkeley, 1993 (with T. Don Tilley)PDF, Berkeley, 1993 (with T. Don Tilley)

•Assistant Professor, Caltech,1999-2004Assistant Professor, Caltech,1999-2004•Associate Professor, Caltech, 2004-2006Associate Professor, Caltech, 2004-2006•Professor, Caltech, 2006-2007Professor, Caltech, 2006-2007•W.M. Keck Professor of Energy, MIT, 2007-2010W.M. Keck Professor of Energy, MIT, 2007-2010•Brenn Professor of Chemistry, Caltech 2010-Brenn Professor of Chemistry, Caltech 2010-

presentpresent

Research Interests and PublicationsResearch Interests and PublicationsResearch Interests and PublicationsResearch Interests and Publications

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•Development of new reagents and methods for Development of new reagents and methods for organic synthesis, with an emphasis on organic synthesis, with an emphasis on asymmetric catalysis; elucidation of reaction asymmetric catalysis; elucidation of reaction mechanismsmechanisms

•Multi-Electron Redox Reactions of Small Molecule Substrates Using Late First Row Transition Metals Multi-Electron Redox Reactions of Small Molecule Substrates Using Late First Row Transition Metals •Dicopper Cores as Multi-electron Redox Shuttles and Photochemical ReductantsDicopper Cores as Multi-electron Redox Shuttles and Photochemical Reductants•Electrocatalytic Hydrogen Evolution at Positive PotentialsElectrocatalytic Hydrogen Evolution at Positive Potentials•Zwitterionic Approach to Catalysis at Late Transition Metal CentersZwitterionic Approach to Catalysis at Late Transition Metal Centers

•203 publications; 95 JACS, 36 ACIE, 1 Science.203 publications; 95 JACS, 36 ACIE, 1 Science.

•224 publications; 52 JACS, 11 ACIE, 1 Nature, 1 Science224 publications; 52 JACS, 11 ACIE, 1 Nature, 1 Science

•Fu and Peters have collaborated on 5 other papers: 3 JACS, 1 ACIE, and 1 ScienceFu and Peters have collaborated on 5 other papers: 3 JACS, 1 ACIE, and 1 Science

C-N bond Formation: Who needs it? C-N bond Formation: Who needs it? C-N bond Formation: Who needs it? C-N bond Formation: Who needs it?

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(a) Roughley, S. D.; Jordan, A. M. J. Med. Chem. 2011, 54, 3451.(b) Carey, J. S.; Laffan, D.; Thomson, C.; Williams, M. T. Org. Biomol. Chem. 2006, 4, 2337.

Process ChemProcess ChemProcess ChemProcess Chem

•A survey of reactions used in Process A survey of reactions used in Process Chem at GSK, Pfizer and Astra Zeneca.Chem at GSK, Pfizer and Astra Zeneca.

•Out of small molecule drugs (<550 Out of small molecule drugs (<550 MW), 90% contained nitrogen.MW), 90% contained nitrogen.

•Heteroatom alkylation/arylation Heteroatom alkylation/arylation represented the largest class of represented the largest class of reactions (19%)reactions (19%)


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Med ChemMed ChemMed ChemMed Chem•A survey of reactions used in A survey of reactions used in

Med Chem at GSK, Pfizer and Med Chem at GSK, Pfizer and Astra Zeneca from 2008 to 2011 Astra Zeneca from 2008 to 2011

•23.1% included heteroatom 23.1% included heteroatom alkylation/arylation (also largest alkylation/arylation (also largest class of reactions).class of reactions).


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1.1. SSNN2:2: Widely-used. Issues with overalkylation and poor reactivity for Widely-used. Issues with overalkylation and poor reactivity for secondary alkyl halides.secondary alkyl halides.

2.2. Reductive alkylations: Reductive alkylations: Can be one-pot or using preformed imine.Can be one-pot or using preformed imine.Need better methods for bulk amide reduction step.Need better methods for bulk amide reduction step.

3.3. Nucleophilic Aromatic Substition: Nucleophilic Aromatic Substition: SSNNAr/ANRORC/SAr/ANRORC/SNRNR1.1.For electron-deficient systems.For electron-deficient systems.

4.4. Buchwald-Hartwig CouplingsBuchwald-Hartwig Couplings

Transition-metal Mediated C-N bond formationTransition-metal Mediated C-N bond formationTransition-metal Mediated C-N bond formationTransition-metal Mediated C-N bond formation

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•Early work by Migita in Early work by Migita in 1983.1983.

•Limited scope, but Limited scope, but conditions are mild conditions are mild compared to other compared to other methods at the time.methods at the time.

•Sn toxicity problematic.Sn toxicity problematic.•Buchwald and Hartwig Buchwald and Hartwig

studied this reaction in studied this reaction in detail.detail.

(a)Kosugi, M.; Kameyama, M.; Migita, T. Chem. Lett. 1983, 927 (b) Paul, F.; Patt, J.; Hartwig, J. Am. Chem. Soc.1994,116, 5969(c) Guram, A.; Buchwald, S.J. Am. Chem. Soc.1994, 116, 7901

•Developed a tin-free Developed a tin-free methodology utilizing a methodology utilizing a bulky base.bulky base.

•Scope was limited to Scope was limited to secondary amines due to secondary amines due to competing β-hydride competing β-hydride elimination.elimination.

•Encouraged the Encouraged the development of novel development of novel phosphine ligands to phosphine ligands to improve the reaction improve the reaction generality.generality.

(a) Wolfe, J.; Wagaw, S.; Buchwald, S. J. Am. Chem. Soc.1996,118, 7215(b) Driver, M.; Hartwig, J.J. Am. Chem. Soc.1996,118, 7217.


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•Since 1994, vast amount of Since 1994, vast amount of research devoted to extending the research devoted to extending the reaction generality. reaction generality.

•Can now be applied to a vast array Can now be applied to a vast array of systems.of systems.

•Many variables to consider when Many variables to consider when designing a Pd-catalyzed amination designing a Pd-catalyzed amination reaction.reaction.

(a) Surry, D. S.; Buchwald, S. L. Chem. Sci. 2010, 2, 27.


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““Borrowing Hydrogen StrategyBorrowing Hydrogen Strategy””““Borrowing Hydrogen StrategyBorrowing Hydrogen Strategy””

(a) Hamid, M. H. S. A.; Allen, C. L.; Lamb, G. W.; Maxwell, A. C.; Maytum, H. C.; Watson, A. J. A.; Williams, J. M. J. J. Am. Chem. Soc. 2009, 131, 1766.(b) For a review on the borrowing hydrogen strategy, see: Hamid, M. H. S. A.; Slatford, P. A.; Williams, J. M. J. Adv. Synth. Catal. 2007, 349, 1555.


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•Most methods require activated, electron deficient alkenes.Most methods require activated, electron deficient alkenes.• Issue with high activation energy resulting electrostatic repulsions Issue with high activation energy resulting electrostatic repulsions

between the amine lone pair and incoming electron-rich -bond 𝜋between the amine lone pair and incoming electron-rich -bond 𝜋of the alkenes. of the alkenes.

(a) Zhu, S.; Niljianskul, N.; Buchwald, S. L. J. Am. Chem. Soc. 2013,135, 15746.(b) For a related methodology, see: Miki, Y.; Hirano, K.; Satoh, T.; Miura, M. Angew. Chem. 2013, 52, 10830.(c) For more on hydroamination, see: Reznichenko, A. L.; Nawara-Hultzsch, A. J.; Hultzsch, K. C. Topics in Current Chemistry (Springer), 2013, 343, 191–260.

Anti-MarkovnikovAnti-Markovnikov

Development of the Ullmann ReactionDevelopment of the Ullmann ReactionDevelopment of the Ullmann ReactionDevelopment of the Ullmann Reaction

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•1901: Synthesis of 1901: Synthesis of biaryls using biaryls using stoichiometric Cu.stoichiometric Cu.

•1903: Formation of C-N 1903: Formation of C-N bond using stoichiometric bond using stoichiometric Cu.Cu.

Another Successful Collaboration!Another Successful Collaboration!Another Successful Collaboration!Another Successful Collaboration!

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•1905: Use of catalytic Cu to 1905: Use of catalytic Cu to form aryl ethers.form aryl ethers.

•1906: Use of catalytic 1906: Use of catalytic Cu for aryl amine Cu for aryl amine synthesissynthesis

•Harsh conditions gave room for much improvement Harsh conditions gave room for much improvement and knowledge to be gained.and knowledge to be gained.

Modern Improvements to Ullmann ReactionsModern Improvements to Ullmann ReactionsModern Improvements to Ullmann ReactionsModern Improvements to Ullmann Reactions

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Goodbrand. H; Hu, N. J. Org. Chem. 1999,64, 670.

Shafir. A; Buchwald, S. J. Am. Chem. Soc. 2006, 128, 8742.

For more examples of modernized Ullman reactions/Cu-chemistry, see: (a) Lin, H.; Sun, D. Org. Prep. Proc. Int. 2013, 45, 341.(b) Beletskaya, I. P.; Cheprakov, A. V. Organometallics 2012, 31, 7753. (c) Evano, G.; Blanchard, N.; Toumi, M. Chem. Rev. 2008, 108, 3054.(d) Monnier, F.; Taillefer, M. Angew. Chem. 2009, 48, 6954.

Proposed MechanismProposed MechanismProposed MechanismProposed Mechanism

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For more mechanistic details, see: (a) J. W. Tye, Z. Weng, A. M. Johns, C. D. Incarvito, J. F. Hartwig, J. Am. Chem. Soc. 2008, 130, 9971. (b) R. Giri, J. F. Hartwig, J. Am. Chem. Soc. 2010, 132, 15860. (c) G. O. Jones, P. Liu, K. N. Houk, S. L. Buchwald, J. Am. Chem. Soc. 2010, 132, 6205. (d) H.-Z. Yu, Y.-Y. Jiang, Y. Fu, L. Liu, J. Am. Chem. Soc. 2010,132, 18078. (e) Casitas, A.; Ribas, X. Chem. Sci. 2013, 4, 2301.

1.1. Formation of Cu(I)-amide species.Formation of Cu(I)-amide species.2.2. Oxidative addition to generate Cu(III) Oxidative addition to generate Cu(III)

intermediateintermediate3.3. Reductive elimination to generate C-N Reductive elimination to generate C-N

product and regenerate Cu(I)-Xproduct and regenerate Cu(I)-X

Yoshikai, N.; Nakamura, E. Chem. Rev. 2012, 112, 233.

CuCuII-Cu-CuIIIIII CuCuII-Cu-CuIIIIII CuCuII-Cu-CuIIII CuCuII-Cu-CuIIII

1.1. Formation of Cu(I)-amide species.Formation of Cu(I)-amide species.2.2. Single electron transfer generates the aryl Single electron transfer generates the aryl

radical and Cu(II) species.radical and Cu(II) species.3.3. Aryl radical undergoes bond formation with Aryl radical undergoes bond formation with

the nucleophile, and in the process, Cu(II) is the nucleophile, and in the process, Cu(II) is reduced to Cu(I).reduced to Cu(I).

Project Origins: Exploiting Inorganic Chemistry…Project Origins: Exploiting Inorganic Chemistry…Project Origins: Exploiting Inorganic Chemistry…Project Origins: Exploiting Inorganic Chemistry…

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[Cu(PNP)][Cu(PNP)]22

•Original purpose was to develop luminescent materials for use in OLED devices.Original purpose was to develop luminescent materials for use in OLED devices.•Designed an amido-bridged bimetallic copper system, which was an excellent luminophore, Designed an amido-bridged bimetallic copper system, which was an excellent luminophore, •Quantum yield: φ = 0.68 in cyclohexane, Lifetime: τ > 10 μs (unprecedented in Cu(I) complexes)Quantum yield: φ = 0.68 in cyclohexane, Lifetime: τ > 10 μs (unprecedented in Cu(I) complexes)

(a) Harkins, S. B.; Peters, J. C. J. Am. Chem. Soc. 2005, 127, 2030–2031.

Project Origins: Exploiting Inorganic Chemistry…Project Origins: Exploiting Inorganic Chemistry…Project Origins: Exploiting Inorganic Chemistry…Project Origins: Exploiting Inorganic Chemistry…

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•Extended to designing easy to synthesize derivatives, Extended to designing easy to synthesize derivatives, including a novel example of a carbazolate Cu including a novel example of a carbazolate Cu complex.complex.

• (Ph(Ph33P)P)22Cu(cbz) exhibited cyan emission at 461 nm and Cu(cbz) exhibited cyan emission at 461 nm and reported the highest quantum yield (0.24) and reported the highest quantum yield (0.24) and lifetimes (11.7) out of the other Cu complexes.lifetimes (11.7) out of the other Cu complexes.

a.) Lotito, K. J.; Peters, J. C. Chem. Commun. 2010, 46, 3690.

Starting with a Bang!Starting with a Bang!Starting with a Bang!Starting with a Bang!

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•Goal:Goal: Provide direct experimental evidence for a Provide direct experimental evidence for a SET/radical process for Ullman C-N couplings.SET/radical process for Ullman C-N couplings.

•Develop milder conditions for C-N bond formation Develop milder conditions for C-N bond formation using a photointiated process. using a photointiated process.

Creutz, S. E.; Lotito, K. J.; Fu, G. C.; Peters, J. C. Science 2012, 338, 647.

Preliminary ResultsPreliminary ResultsPreliminary ResultsPreliminary Results

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•Reactivity parallels radical Reactivity parallels radical conditions;conditions;

• I>Br>Cl.I>Br>Cl.


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•Conducted cyclized experiment Conducted cyclized experiment using a well-known radical probe.using a well-known radical probe.

•Cyclization product obtained.Cyclization product obtained.•The lack of reactivity has been The lack of reactivity has been

used previously to disprove a used previously to disprove a radical-based mechanism.radical-based mechanism.

•However could form via concerted However could form via concerted oxidative addition, migratory oxidative addition, migratory insertion, and reductive insertion, and reductive eliminationelimination

•Deuterium-labelling experiment Deuterium-labelling experiment supports radical mechanism.supports radical mechanism.

• If syn-insertion was in play, only If syn-insertion was in play, only 6d should form.6d should form.

•Checked to confirm SM does not Checked to confirm SM does not isomerize. isomerize.


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•Competition experiment reveals Competition experiment reveals preference for chlorobenzonitrile.preference for chlorobenzonitrile.

• Indicative of SET-based Indicative of SET-based mechanism as chlorobenzonitrile mechanism as chlorobenzonitrile has a more favourable reduction has a more favourable reduction potential compared to 1-potential compared to 1-bromonapthalene.bromonapthalene.

• (-2.07 V vs. -2.17 V vs. SCE)(-2.07 V vs. -2.17 V vs. SCE)

““Ullmann C-N Coupling Is Possible with Photoinitiation!Ullmann C-N Coupling Is Possible with Photoinitiation!””““Ullmann C-N Coupling Is Possible with Photoinitiation!Ullmann C-N Coupling Is Possible with Photoinitiation!””

Improving Reaction GeneralityImproving Reaction GeneralityImproving Reaction GeneralityImproving Reaction Generality

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•Can generate Cu-carbazolide complex in situ using CuI.Can generate Cu-carbazolide complex in situ using CuI.•Scope extended to alkyl iodides, alkyl bromides.Scope extended to alkyl iodides, alkyl bromides.•Lithium plays an important role. Lithium plays an important role.

Bissember, A. C.; Lundgren, R. J.; Creutz, S. E.; Peters, J. C.; Fu, G. C. Angew. Chem. 2013, 52, 5129.


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•Neopentyl iodide gives good conversion; a notorious Neopentyl iodide gives good conversion; a notorious poor electrophile in Spoor electrophile in SNN2 alkylation reactions. 2 alkylation reactions.

•Reaction is stereospecific; Reaction is stereospecific; transtrans-product obtained in -product obtained in good dr.good dr.

•Also a complementary method to SAlso a complementary method to SNN2 (expect 2 (expect inversion).inversion).


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•Hypothesized that Li[Cu(carbazolide)Hypothesized that Li[Cu(carbazolide)22] ] is a reactive intermediate.is a reactive intermediate.

•Synthesized Li complex and subjected Synthesized Li complex and subjected to reaction conditions.to reaction conditions.

• In the presence of light, the same yield In the presence of light, the same yield is obtained, suggesting this Li-Cu-is obtained, suggesting this Li-Cu-complex could be an intermediate.complex could be an intermediate.


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•Reaction extended to formation of C-S bond formation.Reaction extended to formation of C-S bond formation.•Demonstrated that other nucleophiles (i.e: thiols) could be Demonstrated that other nucleophiles (i.e: thiols) could be

utilized.utilized.•Reaction thought to proceed via a Cu(I)-thiolate complex.Reaction thought to proceed via a Cu(I)-thiolate complex.

Uyeda, C.; Tan, Y.; Fu, G. C.; Peters, J. C. J. Am. Chem. Soc. 2013, 135, 9548–9552.


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•Reaction extended other nitrogen nucleophiles/ common Reaction extended other nitrogen nucleophiles/ common pharmacophorespharmacophores

•Wavelength of light important (254 nm vs. 350 nm for carbazoles).Wavelength of light important (254 nm vs. 350 nm for carbazoles).•Propensity for arylation parallels pKa of N-nucleophiles.Propensity for arylation parallels pKa of N-nucleophiles.

Ziegler, D. T.; Choi, J.; Muñoz-Molina, J. M.; Bissember, A. C.; Peters, J. C.; Fu, G. C. J. Am. Chem. Soc. 2013, 135, 13107.

Photoinduced Amination!Photoinduced Amination!Photoinduced Amination!Photoinduced Amination!

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•Goal:Goal: Extend the methodology to non-aromatic nucleophiles (i.e: amides). Extend the methodology to non-aromatic nucleophiles (i.e: amides).

Do, H.-Q.; Bachman, S.; Bissember, A. C.; Peters, J. C.; Fu, G. C. J. Am. Chem. Soc. 2014, 136, 2162–2167.

OptimizationOptimizationOptimizationOptimization

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• In parallel with previous papers, Li played In parallel with previous papers, Li played an important role.an important role.

•Higher wavelengths and 100 W Hg lamp Higher wavelengths and 100 W Hg lamp gave trace yields.gave trace yields.

•Can use 36 W UVC air treatment lamp, Can use 36 W UVC air treatment lamp, instead of Luzchem Photoreactor.instead of Luzchem Photoreactor.

•Air and moisture tolerant.Air and moisture tolerant.

Honeywell 36 W UVCHoneywell 36 W UVCair treatment lampair treatment lamp

Honeywell 36 W UVCHoneywell 36 W UVCair treatment lampair treatment lamp Luzchem PhotoreactorLuzchem PhotoreactorLuzchem PhotoreactorLuzchem Photoreactor

ScopeScopeScopeScope

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•Good yields for a wide range of functional Good yields for a wide range of functional groups.groups.

•Alkyl bromides, alkyl iodides and one Alkyl bromides, alkyl iodides and one example of an alkyl chloride works. example of an alkyl chloride works.


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•Aliphatic and aromatic amides both gave Aliphatic and aromatic amides both gave excellent conversions with good functional excellent conversions with good functional group tolerance. group tolerance.

•Sterically-demanding amides worked well.Sterically-demanding amides worked well.•No overalkylation observed.No overalkylation observed.•Alkyl iodides used due to poor solubility.Alkyl iodides used due to poor solubility.


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•Lactam, 2-oxazalindinone, and α,β-unsaturated amide substrates also were Lactam, 2-oxazalindinone, and α,β-unsaturated amide substrates also were suitablesuitable

Med ChemMed ChemMed ChemMed Chem

•Synthesized opiod receptor agonist in 4 steps, Synthesized opiod receptor agonist in 4 steps, compared to 6 reported by an Eli Lilly patent.compared to 6 reported by an Eli Lilly patent.

Other ApplicationsOther ApplicationsOther ApplicationsOther Applications

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Flow ChemistryFlow ChemistryFlow ChemistryFlow Chemistry

•Developed flow conditions to produce 10.1 g of Developed flow conditions to produce 10.1 g of productproduct

Synthesis of Cu-Nu complexSynthesis of Cu-Nu complexSynthesis of Cu-Nu complexSynthesis of Cu-Nu complex

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•Synthesized Cu(I)-oxazolindinyl tetramer and characterized by X-ray crystallography.Synthesized Cu(I)-oxazolindinyl tetramer and characterized by X-ray crystallography.•Utilized this Cu(I)-complex in the photo reaction, which gave comparable conversions to CuI.Utilized this Cu(I)-complex in the photo reaction, which gave comparable conversions to CuI.•Suggests Cu(I)-amidate might be a potential intermediate.Suggests Cu(I)-amidate might be a potential intermediate.

Competition ExperimentsCompetition ExperimentsCompetition ExperimentsCompetition Experiments

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•Competition experiments between alkyl Competition experiments between alkyl halides gave reactivity trends indicative halides gave reactivity trends indicative of a radical pathway. of a radical pathway.

• I>Br>ClI>Br>Cl

•Cyclization experiments generate Cyclization experiments generate endo:exo ratios in parallel with radical endo:exo ratios in parallel with radical pathways.pathways.

• Indicative of common radical Indicative of common radical intermediate.intermediate.

(a) For more details on radical cyclization, see: Hackmann, C.; Schäfer, H. J. Tetrahedron 1993, 49, 4559.

Proposed Catalytic CycleProposed Catalytic CycleProposed Catalytic CycleProposed Catalytic Cycle

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•Cu(I)-amidate complex undergoes photo excitation.Cu(I)-amidate complex undergoes photo excitation.•SET generates the alkyl radical which undergoes a C-N bond forming event.SET generates the alkyl radical which undergoes a C-N bond forming event.•Formation of product regenerates the Cu halide.Formation of product regenerates the Cu halide.•Admittedly intermediates are simplified, as anionic Cu species have been Admittedly intermediates are simplified, as anionic Cu species have been

isolated and used as intermediates in these reactions.isolated and used as intermediates in these reactions.

Concluding RemarksConcluding RemarksConcluding RemarksConcluding Remarks

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•Developed a photo induced process for alkylation of amides with Developed a photo induced process for alkylation of amides with unactivated secondary halides. unactivated secondary halides.

•Applicable to a wide-range of substrates in varying sterics and electronics.Applicable to a wide-range of substrates in varying sterics and electronics.•Mechanistic studies suggestive of radical pathway involving a Cu(I)-Mechanistic studies suggestive of radical pathway involving a Cu(I)-

amidate complex.amidate complex.•More studies needed to fully elucidate this mechanistic pathway.More studies needed to fully elucidate this mechanistic pathway.•Goals include further expansion of the scope.Goals include further expansion of the scope.

Pros: Pros: •A nice application of photochemistry.A nice application of photochemistry.•Use of Cu over Pd (cost, toxicity)Use of Cu over Pd (cost, toxicity)•Can be applied to flow chem.Can be applied to flow chem.•Complementary method towards accessing alkylated amides.Complementary method towards accessing alkylated amides.•No overalkylation.No overalkylation.•Mild reaction conditions (rt)Mild reaction conditions (rt)Cons:Cons:•Use of alkylating agents (not ideal for late-stage functionalization)Use of alkylating agents (not ideal for late-stage functionalization)•Long reaction times (24 h)Long reaction times (24 h)•Need for specialty glassware (i.e: quartz flasks) and equipment.Need for specialty glassware (i.e: quartz flasks) and equipment.

MORAL: “It’s not what you look at that matters, it's what you see.” ― Henry David Thoreau

http://www.goodreads.com/author/show/10264.Henry_David_Thoreau

carolyn l. ladd literature meeting april 9, 2014

Documents

associate professor

grubbsassistant professor

altair professor of

brenn professor of chemistry

don tilleyassistant

keck professor of energy

sciencecn bond formation

b carey