New
techniques for the generation of C-N bonds are of tremendous current interest,
especially reactions involving direct amination of common feedstocks such as
olefins and alkynes. A reaction used commercially for the generation of some
amines (e.g. tert-butylamine) is
the hydroamination of an olefin. The reaction merges perfect atom economy with
thermodynamic feasibility. However, the kinetic barrier to the reaction is
quite large and catalysis is a necessity. Hydroamination of unactivated olefins
would provide a valuable tool for both the commodity and fine chemical
industries.
Currently,
catalysts effective for the hydroamination of activated olefins and alkynes are
being developed. Metals of certain designs from across the periodic table may
catalyze the reaction. However, titanium complexes have several advantages.
First, titanium is the 2nd most abundant transition element in the
earthÕs crust (after iron) and is quite inexpensive relative to many of the
later metals, e.g. palladium. Consequently, catalyst loadings are much less a
concern. Second, titanium is readily removed from products by flushing through
an alumina or silica plug. Third, on hydrolysis the metal containing product is
TiO2, a nontoxic compound found in many of the foods you buy from the
store and toothpastes. Fourth, titanium complexes have provided the greatest
substrate scope and activity for intermolecular alkyne hydroamination of
complexes reported.
We
investigate new catalyst designs for titanium hydroamination in order to expand
the scope, activity, and utility of titanium catalysis in general and
hydroamination in particular.
Titanium
hydroamination has been in the literature since early reports of intermolecular
hydroamination by Rothwell and coworkers and intramolecular reactions by the
group of Livinghouse. The most thoroughly investigated catalysts from outside
our group contain cyclopentadienyl ancillary ligands. Intermolecular
hydroamination with Cp-based catalysts have been reported by the groups of
Bergman, Doye, Beller, and others. Our group has focused exclusively on non-Cp
based ancillary ligands for this transformation. Pyrrolyl ligands provide a
near optimal mix of electronics, sterics, and ease of synthesis for
hydroamination and potentially many other reactions.
A
simplified mechanistic scheme adapted from the seminal work of Bergman and
coworkers on zirconium hydroamination is shown below.
Electronically,
the pyrrolyl group provides a Lewis acidic metal center. The mechanism for
hydroamination above bears many things in common with the Chauvin mechanism for
olefin metathesis (e.g. d0 metal centers and [2 + 2] cyclizations
with metal-ligand multiple bonds). Because Schrock and coworkers have shown
definitively that reactivity increases with increasing metal Lewis acidity, we
sought more Lewis acidic complexes for the catalysis. Early transition metal
amides have the requisite stability desired for an ancillary ligand, but are
excellent pi-donors often quenching the Lewis acidity. Pyrrole is
an aromatic compound that must use the nitrogen lone pair to reach the
requisite 6 pi-electrons. As a result, pyrrolyl can be used while
retaining the Lewis acidity of the metal center.
Synthetically,
we can take advantage of the Mannich reaction and other standard organic
techniques to prepare multidentate pyrrolyl ligands in a single step.
Two
examples of the catalyst designs are shown below. Both complexes are readily
prepared by addition of the protio ligands to Ti(NMe2)4
in high yields and may be generated in situ if isolation of the air-sensitive
complexes is undesirable.
These reactions have been
applied to alpha,beta-unsaturated imine synthesis and pyrrole synthesis.
Using similar catalysts we have
explored the related reaction of alkyne hydrohydrazination to generate
hydrazones and indoles.
ÒTitanium
Pyrrolyl Complexes: Unusual Electronic and Structural Characteristics Imposed
by the N, N-di(pyrrolyl-a-methyl)-N-methylamine (dpma) LigandÓ, Harris, S. A.; Ciszewski,
J. T.; Odom, A. L. Inorg. Chem. 2001, 40,
1987-1988.
ÒTi(NMe2)4 as a Precatalyst for
Hydroamination of Alkynes with Primary AminesÓ, Shi, Y.; Ciszewski, J. T.;
Odom, A. L. Organometallics 2001, 20,
3967-3969 and Organometallics 2002, 21,
5148.
ÒHydroamination of alkynes catalyzed by a titanium
pyrrolyl complexÓ, Cao, C.; Ciszewski, J. T.; Odom, A. L. Organometallics 2001, 20, 5011-5013 and Organometallics 2002, 21, 5148.
ÒTitanium Catalyzed Intermolecular Alkyne
Hydroamination by 1,1-Disubstituted HydrazinesÓ, Cao, C.; Shi, Y.; Odom, A. L. Org.
Lett. 2002, 4,
2853-2856.
ÒInsertion of an Electron-Rich
Alkyne into a Molybdenum Amido BondÓ, Katayev, E.; Li, Y.; Odom, A. L. Chem.
Commun. 2002, 838-839.
ÒGroup-4 h1-pyrrolyl
complexes incorporating N,N-di(pyrrolyl-a-methyl)-N-methylamineÓ,
Li, Y.; Turnas, A.; Ciszewski, J. T.; Odom, A. L. Inorg. Chem. 2002, 41, 6298.
ÒTitanium Dipyrrolylmethane Derivatives: Rapid
Intermolecular Alkyne HydroaminationÓ, Shi, Y.; Hall, C.; Ciszewski, J. T.; Cao, C.;
Odom, A. L. Chem. Commun. 2003, 586-587.
ÒTitanium Hydrazido Complexes: Synthesis, Structure,
Reactivity, and Relevance to Alkyne HydroaminationÓ, Li, Y.; Odom, A. L. J.
Am. Chem. Soc. 2004, 126, 1794-1803.
ÒSynthesis and Group-4 Complexes of tri(pyrrolyl-a-methyl)amine (tpa)Ó, Shi, Y.; Cao, C.; Odom, A. L. Inorg. Chem. 2003, 42, 275-281.
ÒPyrrole Syntheses Based on Diyne HydroaminationÓ,
Ramanathan, B.; Keith, A.; Armstrong, D.; Odom, A. L., Org. Lett. 2004, 6, 2957-2960.
Òa,b-Unsaturated Imines from Titanium
Hydroamination and Functionalization by C–H ActivationÓ, Cao, C.; Li, Y.;
Shi, Y.; Odom, A. L. Chem. Commun.
2004, 2002-2003.
For a brief review see:
ÒNew C–N and C–C Bond
Forming Reactions Catalyzed by Titanium ComplexesÓ, Odom, A. L. Dalton Transactions (Perspective Article and Cover) 2005, 225-233.