Houk Research Group
 
Individual Research Projects
Potential Energy Surfaces for Diradical-Mediated Rearrangements and the Role of Dynamics
Christopher P. Suhrada and K. N. Houk

Bicyclo[3.1.0]hex-2-ene.
Labeled bicyclo[3.1.0]hex-2-ene rearranges to degenerate products in unequal proportions, despite the intermediacy of a single, symmetrical diradical structure. We have mapped the PES and concluded that the central diradical, because it has essentially no energy minimum, behaves more as a transition state than as an intermediate. Accordingly, the three products are formed by equi-energetic but geometrically non-equivalent paths. Based on our data, Charles Doubleday (Columbia University) performed molecular dynamics simulations, illustrated below, which show how the PES shape influences reaction trajectories to produce the experimentally observed distribution.
6-Methylenebicyclo[3.2.0]hept-2-ene.
Experiments by Dieter Hasselmann’s group (Ruhr-Universität Bochum) demonstrated that labeled 6-methylenebicyclo[3.2.0] hept-2-ene rearranges to 5-methylenenorbornene with partial regio- and steroselectivity. Our theoretical findings attribute much of the observed selectivity to a stepwise mechanism with multiple, non-degenerate paths from reactant to intermediates and from intermediates to products, as well as incomplete conformational equilibration of diradicals. A fit to the experimental data implicates a dynamical bifurcation of some bond-breaking trajectories toward either to the intermediate, on one hand, or directly to the product, on the other (illustrated below).
Molybdenum-Catalyzed Asymmetric Allylations
J. A. R. Luft and K. N. Houk

Molybdenum-catalyzed asymmetric allylations have become a powerful method to afford a branched substrate in high yield and enantiomeric excess from either the linear or branched reagent. Shane Krska and his co-workers at Merck Research Laboratories have been working to understand the mechanism of this unusual reaction. The reaction is known to proceed via a π -allyl complex. The reaction requires an external source of CO. Previous studies have shown that both oxidative addition and nucleophilic attack occur with retention of configuration. Computational studies using Hartree-Fock and Density Functional Theory have begun on the known and anticipated intermediates. Preliminary calculations led to the potential reaction mechanism of calculated intermediates are shown.
Krska, S. W.; Hughes, D. L.; Reamer, R. A.; Mathre, D. J.; Sun, Y. “The Unusual Role of CO Transfer in Molybdenum-Catalyzed Asymmetric Alklyations” J. Am. Chem. Soc. 2002, 124, 12656-12657.
Intramolecular Halocyclizations
J. A. R. Luft and K. N. Houk

Intramolecular halocyclizations have been previously studied both experimentally and theoretically. We are currently investigating a highly diastereoselective bromolactolization. Kazunori Koide at the University of Pittsburgh reasoned that reacting 1 with NBS in water would afford a diastereomeric mixture of bromolactol. He planned to separate the desired stereoisomer and proceed with his synthesis of FR901464.1 Unexpectedly, the cis isomer was formed in high yield (75%). A substrate with opposite stereochemistry at the siloxy substituent, 3, afforded 4 with even higher selectivity (95%). Computational studies show that the strong conformational preference of the siloxy group determines the lowest energy conformers. The conformational preferences of the remaining substituents affect the relative stabilities of the cis and trans isomers. These stabilities explain the observed stereoselectivities.
1. Albert, B. J.; Koide, K. “Synthesis of a C4-epi-C1-C6 Fragment of FR901464 Using a Novel Bromolactolization,” Org. Lett. 2004, 6, 3655-3658.
An Unexpected Radical Rearrangement En Route to Avermectin B1
J. A. R. Luft and K. N. Houk

During the synthesis of an Avermectin B1 analogue, chemists observed an unexpected radical rearrangement under Nishiyama conditions for radical ring formation. The expected product, containing a cyclohexyl ring, was observed in less than 5%. The major product was a five-five-five fused ring system from an apparent radical ring rearrangement. Computational methods have been used to explain the cause of the rearrangement. Computational efforts indicate that the macrocycle is not necessary to afford the rearrangement. Experimental investigations are currently focused on radical reactions that might afford the rearranged products. One proposed reaction would yield a substituted cyclopentyl ring in two to three steps starting from a Diels-Alder reaction of substrates of interest.
Nickel Coupling Mechanism
Patrick R. McCarren and K. N. Houk

The intermolecular, stereoselective reaction below may have great utility.
How does it work? Computational chemistry is testing proposed mechanisms such as the stereocenter-forming step shown below. Our goal is to gain mechanistic insight and a predictive model for future experiments.
Jamison et al. J. Am. Chem. Soc. 2003, 125, 3442-3443.
Understanding the Proficiency of OMP Decarboxyzlase: An Ab Initio Study
Courtney L. Stanton and K. N. Houk

Orotidine 5'-Monophosphate Decarboxylase.
In 1995 the enzyme orotidine 5'-monophosphate decarboxylase (OMP decarboxylase) was declared the most proficient* enzyme known (Radzicka, A.; Wolfenden, R. Science 1995, 267, 90-92). Despite a decade of attention and the proposal of many different hypotheses, the mechanism of ODCase catalysis remains unsolved (for review see Houk, K. N.; Tantillo, D.J.; Stanton, C.; Hu, Y. Topics in Current Chemistry 2004, 238, 1-22).

We have undertaken a theoretical exploration of all relevant reaction mechanisms that have been suggested for OMP decarboxylase by applying density functional methods to small model systems. Our intention is to gain a systematic knowledge of the inherit advantage that one type of catalysis may have over another.
Density Functional Calculations

Table 1. Reaction energetics (kcal/mol) for the decarboxylation of various N-methyl orotic acid derivatives. All calculations done at the B3LYP/6-31+G(d,p) level, using CPCM implicit solvent model with UAKS radii where applicable. ΔGFORM refers to formation of the pictured intermediates from N-methyl orotic acid. pKa values refer to the carbon acidity at C6 for each decarboxylated intermediate and are calculated at the same level of theory and implicit solvent model.
Characterization of Synthetic Linear Motor Molecule Actuation
via Atomic Force Spectroscopy and Computational Modeling
Brian H. Northrop, K. N. Houk, J. Fraser Stoddart, B. Brough, J. J. Schmidt, H.-R. Tseng, and C.-H. Ho

Molecular motors have recently garnered great interest for their potential to convert energy into mechanical work at the micro and nanoscale. Being able to quantitatively measure the amount of energy available to for a molecular scale motor do work is necessary for the characterization, development, and optimization of molecular motors. To this aim, an interdisciplinary combination of synthesis, surface chemistry, single molecule atomic force microscopy (AFM), and theoretical molecular dynamics simulations have been used to characterize the actuation of a synthetic [2]rotaxane-based motor molecule. The specifically designed [2]rotaxane has been synthesized with a dual recognition motif to allow for attachment to both a silicon surface and a gold AFM tip. Molecular dynamics and mechanics calculations were used to map the potential energy surface of the [2]rotaxane and, in conjunction with atomic force measurements, have been used to provide a quantitative description of molecular actuation. These results were further supported by density functional calculations.
Brough, B.; Northrop, B. H.; Schmidt, J. J.; Tseng, H.-R., Houk, K. N.; Stoddart, J. F.; Ho, C.-H. submitted.
Pentacene Physical Properties and Photostability, a Theoretical and Experimental Mechanistic Study
Brian H. Northrop, K. N. Houk, J. Fraser Stoddart, and Elsa Reichmanis

Polycyclic aromatic compounds have shown great promise for use in organic electronic materials. In particular, thin film transistors of pentacene have been shown to exhibit charge carrier mobilities comparable to silicon. However, marketable devices based on pentacene have not been realized due to the ease with which pentacene is photooxidized. The mechanism of photooxidation is believed to proceed via photostimuated electron transfer to oxygen, leading to other products and the loss of any desirable electronic properties, although photooxidation via energy transfer to form singlet oxygen is also reasonable. A greater understanding of the mechanism may lead to the development of substituted pentacenes that overcome the stability problem.

A combination of synthesis, photostability measurements, and theoretical calculations is being used to determine whether pentacene photooxidation occurs via electron or energy transfer. Building upon the work of Anthony, a series of 6,13-disubstituted pentacene derivatives have been synthesized. Photostability measurements are currently being performed in tetrahydrofuran and toluene. Additionally, density functional calculations are being used to predict rates of electron transfer using Marcus theory:



The results should establish the mechanism of photooxidaion and lead to more stable pentacenes.
Maliakal, A.; Raghavachari, K.; Katz, H.; Chandross, E.; Siegrist, T. Chem Mater. 2004, 16, 4980-4986. Anthony, J. E.; Brooks,J. S.; Eaton, D. L.; Parkin, S. R. J. Am. Chem. Soc. 2001, 123, 9482-9483.
Theorectical Studies of Quantum Amplification of Isomerization for Imaging Systems

Joseph E. Norton, Leif P. Olson, and K. N. Houk

Quantum Amplified Isomerization (QAI) is the conversion of a strained-ring reactant into a more stable product via a photoinduced electron-transfer chain reaction where a single photon causes isomerization of many molecules.1

The ring-opening reactions of the radical cations of hexamethyl Dewar benzene (1) and Dewar benzene have been studied using density functional theory and complete active space self-consistent field (CASSCF) calculations. The high quantum yield for ring opening of 1 by a chain mechanism is termed "quantum amplified isomerization" (QAI). Why QAI is efficient for 1 but not other reactions is being studied computationally. Two stable radical cations of 1 have been identified, along with transition states located near avoided crossings. Conical intersections corresponding to observed state crossings have also been located. Ring opening in Dewar benzene and 1 occurs by formation of the radical cation followed by a decrease in the flap dihedral. A rate-limiting Cs transition state leads to a second stable radical cation with an elongated transannular C-C bond and an increased flap dihedral. A thermally-allowed conrotatory-like pathway of Cs symmetry leads to the benzene radical cation. The ease of oxidation of various systems has been evaluated using adiabatic ionization energies and electron affinities. Electron-transfer theory has been applied to 1 to investigate the limiting effects of back-electron transfer as related to the unusual stability of two radical cations. Frequency-dependent indices of refraction are computed from isotropic polarizabilities to evaluate expected changes in optical properties between reactants and products. Compound 1 shows greater contrast in index of refraction than the parent system Dewar benzene. Other systems known to undergo QAI and prospective systems for amplification are under investigation.

1. Evans, T. R.; Wake, R. W.; Sifain, M. M. Tetrahedron Lett. 1973, 701-704.
H/Vinyl Conical Intersections of Hexatrienes as Related to the Hula-Twist Photoisomerization

Joseph E. Norton and K. N. Houk

H/Vinyl Conical Intersections of Hexatrienes. H/vinyl conical intersections are proposed to have a potential role in the photochemical hula-twist isomerization of hexatriene.1 The hula twist is a novel volume-conserving isomerization mechanism for polyenes in rigid media.2,3 Conical intersections involving partial migration of a hydrogen and inversion of a carbon are explored as potential pathways for hula-twist isomerization. Complete active space self-consistent field (CASSCF) and CASPT2 calculations with the 6-31G(d) basis set are used to explore structures that would potentially lead to hula-twist isomerization. These structures are found to be geometrically ideal for a volume-conserving process, but are energetically unfavorable.

Conical Intersections. Conical intersections are efficient radiationless decay channels that play a key mechanistic role in the photochemistry, chemical kinetics, and spectroscopy of polyatomic molecules. Conical intersections, though once thought to be rare, have been found by Robb, Olivucci, Bernardi and their coworkers, as well as other groups, to be essential in the photochemistry of polyenes, azoalkanes, enones, cyclohexadiene, cycloalkene electrocyclic ring-openings, and retinal chromophores.4 Photochemical reactions can involve multiple conical intersections that lack symmetry observed in reactants and products. Consequently, decay to the ground state can occur through structurally and energetically different conical intersections.

1. Wilsey, S.; Houk, K. N. Photochem. Photobiol. 2002,76, 616-621.
2. Liu, R. S. H.; Hammond, G. S. Chem.--Eur. J. 2001, 7, 4536-4544.
3. Liu, R. S. H. Acc. Chem. Res. 2001, 34, 555-562.
4. Robb, M. A.; Garavelli, M.; Olivucci, M.; Bernardi, F. Rev. Comput. Chem. 2000, 15, 87-146.
Electronic Structures and Properties of Twisted Polyacenes
Joseph E. Norton and K. N. Houk

Polyacenes are linear polycyclic aromatic hydrocarbons with properties exploitable for organic electronics. Highly twisted polyacenes with phenyl substituents strategically placed to induce end-to-end twisting of the acene backbone, as illustrated by 1, have been synthesized. Pascal et al.'s recent successful synthesis of a pentacene exhibiting a twist of 144°, 2,1 has prompted us to investigate the effects of twisting on the electronic structures and properties of polyacenes. Such highly twisted molecules are expected to have unique chiroptical properties, and have already been incorporated into organic light-emitting diodes. The use of substituents to overcome chemical instability while maintaining the electronic properties necessary to serve as functional materials in semiconducting devices is currently being explored. In recent years, our group and others have reported on the electronic structures of polyacenes.2,3 The electronic structures of substituted polyacenes are currently being investigated.

The effects of twisting on the electronic structures and properties of polyacenes have been investigated computationally using DFT methods.4 Singlet-triplet (S0-T1) and HOMO-LUMO gaps, and vertical S0-S1 transition energies are marginally affected as a function of end-to-end twist angle. Heptacene remains a disjoint radical. The large twist induced by bulky substituents such as in 2 is predicted to have little influence on electronic structure.
1. Lu, J.; Ho, D. M.; Vogelaar, N. J.; Kraml, C. M.; Pascal, R. A., Jr. J. Am. Chem. Soc. 2004, 126, 11168-11169.
2. Houk, K. N.; Lee, P. S.; Nendel, M. J. Org. Chem. 2001, 66, 5517-5521.
3. Bendikov, M.; Duong, H. M.; Starkey, K.; Houk, K. N.; Carter, E. A.; Wudl, F. J. Am. Chem. Soc. 2004, 126, 7416-7417.
4. Norton, J. E.; Houk, K. N. J. Am. Chem. Soc. 2005, 127, 4162-4163.
Deuterium Tunneling in Triplet o-Methylanthrones: Secondary Alpha Isotope Effects
Luis M. Campos, K. N. Houk, and M. A. Garcia-Garibay

Reactions that proceed at extremely low temperatures represent an interesting example of chemical reactivity due to quantum mechanical tunneling (QMT) contributions from zero-point energy levels. o-Methylanthrones have been demonstrated to react at cryogenic temperatures, along the triplet manifold following photoexcitation, via QMT. In our efforts to understand the factors that affect the sensitivity of QMT towards variable isotopic substitution of the ortho-methyl group, we have studied the photochemistry of 1,4-dimethyl-10H-anthracen-9-one 1, and its isotopologues 1b-1d. The rates of deuterium transfer in the triplet state have been determined by phosphorescence emission, and the tunneling rate constants were obtained. The parent protio compound and 1a reacted faster than our detection timescale, but we have observed a relatively large secondary tunneling isotope effect (TIE) of 2.3 from 1d and 1c. Density Functional Theory calculations were carried out in order to obtain structural information as well as the energies of activation for the H(D)-transfer from zero-point energy levels.
L. M. Campos, M. V. Warrier, K. Peterfy, K. N. Houk, M. A. Garcia-Garibay, submitted.
Theoretical Study of Hydrogen Bonding Promoted Diels-Alder Cycloadditions. Reaction Mechanism and Origins of Enantioselectivity
Ruth Gordillo and Kendall N. Houk

Uncatalyzed and one MeOH molecule promoted Diels-Alder reactions of Rawal's diene with acrolein were found to be asynchronous but concerted processes in the gas phase. Introduction of a second MeOH molecule produces a change in the reaction mechanism. In this case, a stepwise mechanism pathway, involving a zwitterionic intermediate (δ = 0.63 e) was found.

TS1

TS2
Figure 1. Potential-energy profile for Diels-Alder cycloaddition of Rawal's diene with alcrolein (s-trans-endo approach of two MeOH molecules catalyzed reaction in a bifurcated complexation mode). ΔH energies are in kcal/mol. Most relevant distances are shown.1,2
Figure 2. 1,4-butanediol conformers A and B optimized structures. Most stable acrolein-MeOH complexes. In all the cases acrolein displays an s-trans conformation. Enthalpy values are in kcal/mol. Most relevant distances are also shown.1,2
Figure 3 shows one of the calculated transition structures including the TADDOL tetranaphthyl derivative as catalyst. The transition structure search is being performed using a methodology that includes initial molecular mechanic conformational search, and Morokuma's IMOMO calculations with a combination of B3LYP-6-31G(d) and AM1 levels of theory.3 This study will give an explanation for the experimentally observed enantioselectivities.4 In addition, these results will provide valuable information for improving the efficiency of structurally similar catalysts, and for designing new organocatalysts.
1. Calculations performed at the B3LYP/6-31G(d) level of theory.
2. Ruth Gordillo, Travis Dudding, and K. N. Houk. Manuscript in preparation.
3. Maseras, F; Morokuma, K. J. Comput. Chem. 1995, 16, 1170-1179.
4. Huang, Y.; Unni, A. K.; Thadani, A. N.; Rawal, V. H. Nature 2003, 424, 126.
Origins of the High Affinity Binding of the Biotin-(Strept)Avidin Complex
Jason DeChancie and K. N. Houk

DFT and MP2 calculations employing model systems for the (strept)avidin binding site involving the hydrogen bonding and hydrophobic residues to the ureido moiety of biotin have been carried out. Biotin is predicted to be significantly polarized in the binding site. Cooperative hydrogen bonding enhances binding compared to individual interactions. Aspartic acid is the key residue stabilizing the hydrogen bonding network. Aspartic acid is directly hydrogen bonded with biotin in streptavidin and is one residue removed in avidin, and the latter is surprisingly more favorable. This work is an advancement towards the answer to a long lasting question: Why are the majority of protein-ligand interactions so poor in comparison to the biotin-(strept)avidin complex?
Origins of Stereoselectivity in Allylations by Leighton's Silane Reagents
Xiyun Zhang, K. N. Houk, and J. L. Leighton

A diamine-based silane reagent (R,R)-1 has been developed for the asymmetric allylation of aldehydes.1 The mechanism and stereoselectivity of such a reaction has been studied with MP2/6-311++G**//HF/6-31G*. The reaction occurs in a single concerted step. Strain in the 5-membered diazasilane ring is released upon the allylation and hence the reaction is low-barrier and exothermic. The most favorable transition state TS1 suggests the components important for the stereoselectivity: 1) attack of aldehyde O on an apical position of the Si center (anti to an N); 2) an antiperiplanar arrangement of an O lone-pair and the Si-Cl bond in the chair transition state; 3) location of the Cl with the lone-pair anti to the lone-pair of apical N.2 Two less favored transition states, TS2 and TS3, are also shown. TS2 has an synperiplanar arrangement of an O lone-pair and the Si-Cl bond in the chair transition state; in TS3, Cl has its lone-pair syn to the lone-pair of apical N.

Pseudoephedrine-based silane reagent (S,S)-2 has also been developed as a versatile reagent for the enantioselective allylation of aldehyde-derived acetylhydrazones and ketone-derived benzoylhydrazones.3,4 Computational studies on such reactions are in progress.
1. Kubota, K.; Leighton, J. L. Angew. Chem. Int. Ed. 2003, 42, 946.
2. Zhang, X.; Houk, K. N.; Leighton, J. L. Angew. Chem. Int. Ed. 2005, 43, 938.
3. Berger, R.; Rabbat, P. M. A.; Leighton, J. L. J. Am. Chem. Soc. 2003, 125, 9596.
4. Berger, R.; Duff, K.; Leighton, J. L. J. Am. Chem. Soc. 2004, 126, 5686.
Mechanisms of HOONO and MeOONO Rearrangements: A Conformation-Dependent Homolytic Dissociation
Yi-Lei Zhao, K. N. Houk, and Leif P. Olson

Peroxynitrite and related compounds play important roles in biochemistry and atmospheric science. Peroxynitrite may be formed in vivo from superoxide and nitric oxide. The anion is fairly stable, but the protonated form decays to nitrate in seconds at room temperature. Whether NO2 radical exists as an intermediate in the rearrangement has been debated for decades in both experimental and theoretical sides, since active NO2 radical is harmful in physiology but is helpful in tropospheric ozone formation.

Using CCSD, CCSD(T), and CBS-QB3 methods, the O-O bond breaking process is investigated, concluding that the OONO dihedral angle has a remarkably large influence on barriers for the cleavage. A barrier of 18-19 kcal/mol is predicted for RO-ONO dissociation involving a 2A1-like NO2 fragment in TSs from a cis-conformation (green line), while a barrier of 33-34 kcal/mol relative to a 2B2-like TS with trans-conformation (red line).

Notably, the favored cis-pathway is "electronically correct" but "geometrically incorrect" for subsequent N-O bond formation. The imperfect orientation rationalizes some escape of free radicals, in competition with low-barrier RO/NO2 collapse towards RONO2.

For HOONO, the pathway includes a hydrogen-bonded intermediate, OH---ONO, earlier proposed as a source of one-electron oxidant. MeOONO has a similar rearrangement mechanism, but without any hydrogen-bonded intermediate.
Thionitroxide, Formed Reversibly by Cysteine (Protein) plus Nitric Oxide, can Serve as a NO Reservoir or a Precursor Towards S-Nitrosothiol and HNO
Yi-Lei Zhao and K. N. Houk

Nitric oxide (NO) plays important roles in biology. It has been proposed that nitrosothiol (RSNOs) are key derivatives of proteins such as hemoglobin (Hb) in erythrocyte and formed by the reaction of specific cysteines (e.g., Hb-Cys93) and NO by some oxidative process. Through computational studies with DFT, CBS, and G2 methods, we propose that thionitroxides, RSNHO•, can be formed either from thiols and NO or by reduction of SNO-Hb. The purported hemoglobin-SNO in crystal structures is now thought to be a hemoglobin-SNHO species. Formation of this polar species benefits from hydrogen bonds; thereby conformational processes (R/T-Hb) coupled to SNO-Hb formation may now be explained by SNHO-Hb formation.
Crystal structures:
Chan et al. Biochemistry, 1998, 37(47), 16459-16464.
Chan et al. Biochemistry, 2004, 43(1), 118-132.

Y.-L. Zhao, K. N. Houk, submitted.
Theoretical Modeling of the Solvent Dependence of Kinetic Resolution of Phenylethylamine with a Chiral Amide
Arash Jabbari and K. N. Houk

Substantial progress has been made in the development of nonenzymatic acylation catalysts for the kinetic resolution of alcohols. Less attention has been given to nonenzymatic kinetic resolution of chiral amines. Recently Wagner and Mioskowski reported a new and highly enantioselective acylating reagent 1 for the resolution of phenylethylamine and other chiral primary amines with a unique solvent-induced reversal of stereoselectivity.

A quantum mechanical study of the origin of stereoselectivity and the solvent polarity dependence of this reaction is in progress. The mechanism involves a tetrahedral intermediate. The most stable stereoisomers of this intermediate have been computed with B3LYP/6-31G(d) in different solvents. In the gas phase and in solvents with low polarity, the intermediate, 1-R, with the R configuration at the indicated carbon is the most stable form. By increasing the polarity of the solvent, the isomer 1-S with the S configuration becomes the most stable isomer.

The stereoselectivity correlates rather well with solvato-chromic polarity parameters, and ENT.
S. Arseniyadis, A. Valleix, A. Wagner and C. Mioskowski, Angew. Chem. Int. Ed. 2004, 43, 3314. C. Reichardt, Solvents and Solvent Effects in Organic Chemistry, 3rd ed, Wiely-VCH, Weinheim, Germany, 2002.
Quantum Mechanical Studies of Diels-Alder Reactions Involving Furan
Susan N. Pieniazek and K. N. Houk

Jung and researchers utilize Diels-Alder reactions involving furan as a diene (A, Figure 1). These reactions yield versatile oxanorbornenes that have been used in the syntheses of numerous complex targets.1 Substrate inertness2 and the tendency for products to undergo retrocycloaddition3 can cause reaction failure. Exploring these reactions with computational methods provide useful insight into the factors controlling activation and reaction energies. In particular, these reactions are found to be sensitive to the nature and length of tether (B, Figure 1), as well as substituents on the diene, dienophile, and tether (C, Figure 1). This provides structural guidelines to design successful reactions and to prevent cycloaddition failure.
Figure 1. A) Intramolecular Diels-Alder reactions involving furan as a diene. Factors that control the stability of transition states and products include B) length of the tether and C) substituents on the diene, dienophile, and tether.
1. (a) Vogel, P.; Cossy, J.; Plumet, J.; Arjona, O. Tetrahedron, 1999, 55, 13521-13642. (b) Kappe, C. O.; Murphree, S. S.; Padwa, A. Tetrahedron, 1999, 53, 14179-14233. (c) Lipshutz, B. H. Chem. Rev. 1986, 86, 795-819.
2. Wenkert, E.; Moeller, P. D. R.; Piettre, S. R. J. Am. Chem. Soc. 1988, 110, 7188-7194.
3. (a) Bilovic, D.; Stojanac, Z.; Hahn, V. Tetrahedron Lett. 1964, 5, 2071-2074. (b) Kwart, H.; King, K. Chem. Rev. 1968, 68, 415-447.
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Department of Chemistry and Biochemistry
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Kendall N. Houk

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May 5, 2008