Using Natural Abundance of Isotopes to Investigate Chemical Reaction Mechanisms - PowerPoint Presentation

Slide1

Using Natural Abundance of Isotopes to Investigate Chemical Reaction Mechanisms

John Gipson & Victoria RussellUniversity of Utah

Determination of Kinetic Isotope Effects at Natural Abundance

Overview:

The natural abundance of isotopes of a chemical element can provide detailed information about the mechanism of a large range of chemical reactions. Small heavy-atom and secondary hydrogen kinetic isotope effects (KIEs) can be measured with high-precision, simultaneously determining multiple small KIEs at natural abundance using NMR techniques.

Early Examples

Wiki Pages:

http://en.wikipedia.org/wiki/Natural_abundance; http://en.wikipedia.org/wiki/Abundance_of_the_chemical_elements Other References: Martin, G. J.; Martin, M. L. Tetrahedron Lett. 1981, 22, 3525-3528; Pascal, R. A., Jr.; Baum, M. W.; Wagner, C. K.; Rodgers, L. R.; Huang, D.-S. J. Am. Chem. Soc. 1986, 108, 6477-6482; Singleton, D. A.; Thomas, A. A. J. Am. Chem. Soc. 1995, 117, 9357-9358.

Primary Deuterium KIE – Insertion Reaction

Natural Abundance – Diels-Alder Reaction

KIE = 1.05 – 25% enrichment of slower reacting isotopic component at 99%

converstion

(F = fractional conv.).

Probing Mechanism With Singleton Experiment

Gonzalez-James, O. M.; Kwan, E. E.; Singleton, D. A. J. Am. Chem. Soc. 2012, 134, 1914-1917.

Unexpected secondary KIEs give insight into multiple transition states on a bifurcated potential energy surface:

Probing Mechanism With Singleton Experiment

A qualitative depiction of the energy surface (M06, MPW1K, or MP2) for the [2 + 2] cycloaddition of alkene 1 with ketene 2 (see previous slide for reaction):

Gonzalez-James

, O. M.;

Kwan

, E. E.; Singleton, D. A.

J. Am.

Chem

. Soc.

2012

,

134

, 1914-1917

.

Problem 1

References: Corey, E. J.; Noe, M. C.; Grogan, M. J. Tetrahedron Lett. 1996, 37, 4899-4902; Delmonte, A. J.; Haller, J.; Houk, K. N.; Sharpless, K. B.; Singleton, D. A.; Strassner, T.; Thomas, A. A. J. Am. Chem. Soc. 1997, 119, 9907-9908

The OsO4 catalyzed dihydroxylation of olefins was thought to occur by one of the two distinct mechanisms: The 3+2 Corey-Criegee mechanism is concerted, while the 2+2 Sharpless mechanism has a rate determining ring expansion.How would you expect secondary 13C KIEs to be different for each mechanism?

b) Singleton’s method yields the following results: Which pathway is more likely?

Problem 2

References: Lou, Y.;

Horikawa, M.; Kloster, R. A.; Hawryluk, N. A.; Corey, E. J. J. Am. Chem. Soc. 2004, 126, 8916-8918.

In 2004, Corey proposed that dirhodium(II) catalysts 1, which are generally thought to be tetrabridged, may react through a tribridged intermediate 2 based on ligand studies.What is the proposed reaction mechanism for this cycloaddition process?Based on your understanding of KIEs, what would you predict to observe in KIE studies of the alkyne if this proposed mechanism were correct?

1

2

Problem 2 Continued

References: Lou, Y.; Horikawa, M.; Kloster, R. A.; Hawryluk, N. A.; Corey, E. J. J. Am. Chem. Soc. 2004, 126, 8916-8918; Nowlan, D. T., III; Singleton, D. A. J. Am. Chem. Soc. 2005, 127, 6190-6191.

2c. Using natural abundance to determine KIEs, Singleton reported the following results, where an early asynchronous transition state 3 and 4 is proposed. Are these KIE results consistent with Corey’s mechanism above? Do tetrabridged or tribridged rhodium carbenoids account for the observed isotope effects and selectivity?

3

4

Solution 1

References: Corey, E. J.; Noe, M. C.; Grogan, M. J. Tetrahedron Lett. 1996, 37, 4899-4902; Delmonte, A. J.; Haller, J.; Houk, K. N.; Sharpless, K. B.; Singleton, D. A.; Strassner, T.; Thomas, A. A. J. Am. Chem. Soc. 1997, 119, 9907-9908

1. a) For

a concerted mechanism, we would expect the secondary KIEs on each carbon to be normal, large, and nearly equivalent. For a rate determining ring expansion, only one carbon on the olefin should show a significant secondary KIE, not both carbons.

b) The

Singleton method yields large, normal secondary

13

C KIEs on both carbons- this is consistent with the concerted 3+2 Corey-

Criegee

Mechanism.

Solution 2

References: Lou, Y.; Horikawa, M.; Kloster, R. A.; Hawryluk, N. A.; Corey, E. J. J. Am. Chem. Soc. 2004, 126, 8916-8918; Nowlan, D. T., III; Singleton, D. A. J. Am. Chem. Soc. 2005, 127, 6190-6191.

2a. The mechanism proposed to account for the proposed

tribridged

intermediate

2

proceeds through a [2+2] cycloaddition followed by reductive elimination.

2b. If the proposed [2+2] cycloaddition was the prevailing mechanism for this transformation, one would expect to observe a large and comparable KIE for both carbons of the alkyne.

2c. Based on Singletons KIE results, the proposed mechanism in Corey’s report is not consistent with the observed data. The results support a conventional

tetrabridged

carbenoid

mechanism which also suggest an explanation for the selectivity observed, and it does not support a [2+2] cycloaddition of

intermidiate

2

proposed by Corey. It was further shown that

2

is 21.5 kcal/

mol

uphill in energy from the

tetrabridged

alternative

1

. In additional simulations, the

tribridged

intermediates appeared to be resistant to effecting

cyclopropenation

.

Although Singleton was able to identify a viable mechanism for

cyclopropenation

via the

tribridged

structures, only the

tetrabridged

rhodium

carbenoids

can account for the isotope effects and

eneantioselectivity

of the Rh

2

(O

2

CR)

n

(DPTI)

4-

n

reactions. The

tetrabridged

mechanism is the more optimal starting point for ligand design.

Contributed by:

John Gipson and Victoria Russell (Undergraduate students)

University of Utah

2014