Generation of Masked TiIIIntermediates from TiIVAmides via β-H Abstraction or Alkyne Deprotonation: An Example of Ti-Catalyzed Nitrene-Coupled Transfer Hydrogenation

Article abstract of DOI:10.1021/acs.organomet.0c00577

Simple Ti amide complexes are shown to act as sources for masked TiII intermediates via several pathways, as demonstrated through the investigation of a unique Ti-catalyzed nitrene-coupled transfer hydrogenation of 3-hexyne. This reaction proceeds through reduction of azobenzene by a masked TiII catalyst, wherein both amines and 3-hexyne can serve as the hydrogen source/reductant for Ti by forming putative titanaziridines via β-H abstraction or putative titanacyclopentynes via protonolysis, respectively.

Full text of DOI:10.1021/acs.organomet.0c00577

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Generation of Masked TiII Intermediates from TiIV Amides via β‑H
Abstraction or Alkyne Deprotonation: An Example of Ti-Catalyzed
Nitrene-Coupled Transfer Hydrogenation
Adam J. Pearce,† Yukun Cheng,† Rachel J. Dunscomb, and Ian A. Tonks*
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ABSTRACT: Simple Ti amide complexes are shown to act as
sources for masked TiII intermediates via several pathways, as
demonstrated through the investigation of a unique Ti-catalyzed
nitrene-coupled transfer hydrogenation of 3-hexyne. This reaction
proceeds through reduction of azobenzene by a masked TiII catalyst,
wherein both amines and 3-hexyne can serve as the hydrogen
source/reductant for Ti by forming putative titanaziridines via β-H
abstraction or putative titanacyclopentynes via protonolysis,
respectively.
report the reactivity of masked TiII intermediates generated
from simple Ti amides via β-H abstraction or internal alkyne
deprotonation (Figure 1, bottom).
itanium(II) complexes and intermediates play important
1
Troles in various redox reactions, such as Kulinkovich
cyclopropanations,2 alkyne cyclotrimerization,3−5 and many
other annulations.6,7 Common methods for generating low-
valent metals involve reduction of metal halides or β-H
abstraction of alkyl ligands (Figure 1, top).8−10 In many cases,
these low-valent TiII intermediates are trapped or masked via
backbonding into π-acidic ligands. In the interest of expanding
the accessibility of TiII intermediates in catalysis, we herein
The η2-titanaziridine complexes can be easily generated
through β-H abstraction, and their insertion chemistry in the
context of alkene hydroaminoalkylation catalysis is well-
established.11−13 We hypothesized that η2-titanaziridine
complexes could alternately be considered as masked TiII
species for redox transformations, in direct analogy to
chemistry mediated by η2-olefin/titanacyclopropane complexes
(Figure 1, bottom). In fact, Rothwell demonstrated that an η2-
titanaziridine could furnish a Ti imido upon stoichiometric
reaction with azobenzene.14,15 The use of diazenes to capture
these reactive species could ultimately allow for catalytic
nitrene transfer reactions16−18 from simple and readily
available Ti amide compounds.
Following this hypothesis, TiCl2(NMe2)2 was examined as a
catalyst for 3-hexyne cyclotrimerization19 as well as [2 + 2 + 1]
pyrrole synthesis.16 3-Hexyne underwent successful cyclo-
trimerization with 5 mol % of TiCl2(NMe2)2 as the catalyst,
yielding 58% of C6Et6 after 22 h at 145 °C (eq 1)consistent
with the hypothesis that TiII species could be accessed from
Received: August 30, 2020
Figure 1. Masked TiII reagents generated via β-H abstraction by Ti
alkyls (top) or Ti amides (bottom).
https://dx.doi.org/10.1021/acs.organomet.0c00577
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the amide, as cyclotrimerization typically occurs through a
TiII/TiIV mechanism.20−23
Surprisingly, the attempted [2 + 2 + 1] nitrene transfer
reaction (eq 2) did not yield tetraethylpyrrole as the major
product, instead generating a mixture of (Z)- and (E)-N-
phenylhexan-3-imine in 62% yieldthe product of formal
nitrene-coupled hydrogenation of the alkyne. Although
metallacycle protonation by free HNMe2 resulting from β-H
abstraction could account for some imine formation, yields in
excess of the catalyst loading indicate that other mechanisms
and chemical species must at least partly be involved in Ti
redox and hydrogen transfer.
To investigate the source of hydrogen, the reaction was
carried out with perdeuterated 3-hexyne-d10 (eq 3). This
reaction yielded a mixture of 3-d10, 3-d11, and 3-d12 in a ratio of
0.16:0.73:1.0 (eq 3). The predominance of 3-d12 suggests that
3-hexyne is the major hydrogen source (vide infra). Mean-
while, the formation of 3-d10 and mixed product 3-d11 indicates
that HNMe2 (from β-H abstraction of dimethylamide ligand)
also contributes a non-negligible amount of hydrogen. Notably,
based on the catalyst loading, the dimethylamide ligands can
account for the majority of hydrogen for 3-d10 and 3-d11.
However, as H/D scrambling of 3 with 3-hexyne can occur
(see Supporting Information for a scrambling experiment), the
approximate ratio of β-H abstraction versus alkyne deproto-
nation may be underestimated. This reaction is a rare example
of Ti-catalyzed transfer hydrogenation24,25 and a unique
example of nitrene-coupled transfer hydrogenation.
Based on the information above, we propose the mechanism
for nitrene-coupled transfer hydrogenation in Figure 2. Starting
from TiCl2(NMe2)2 (A), two pathways are possible: first,
coordination of 3-hexyne to Ti and subsequent deprotonation
of the propargylic C−H affords titanacyclopentyne complex B
(pathway I). Coordination of another oxidizing π-acid such as
azobenzene could then liberate 2,3,4-hexatriene to furnish a Ti
η2-hydrazido(2−) complex C. Although 2,3,4-hexatriene is not
observed in reaction mixtures, metallacyclopentyne complexes
of group 4 metals have been studied previously,26−29 and this
mechanism best accounts for the poor mass balance in 3-
hexyne (despite 85% conversion of 3-hexyne, less than 50% 3-
hexyne is converted to 3), although we cannot rule out other
dehydrogenation products of 3-hexyne being involved.
Alternately, TiCl2(NMe2)2 can undergo β-H abstraction to
generate an η2-titanaziridine D (pathway II), which could
similarly undergo exchange with azobenzene to liberate N-
methylformimine and generate the Ti η2-hydrazido(2−) C. We
have observed similar π-acid/azobenzene exchange with low-
valent Ti halides during Ti-catalyzed isocyanide amination
reactions.30
Figure 2. Plausible mechanism of hydroamination of 3-hexyne with
azobenzene catalyzed by TiCl2(NMe2)2. Teal and black hydrogens
indicate their origin from −NMe2 or 3-hexyne, respectively.
Ti η2-hydrazido(2−) complexes like C are well-established
to undergo bimetallic scission to Ti imido complexes (E).16,31
From E, [2 + 2] cycloaddition of 3-hexyne yields
azatitanacyclobutadiene F, which can undergo protonolysis
by HNMe2 to liberate the hydroaminated product32−34 and
regenerate TiCl2(NMe2)2. HNMe2 ultimately serves the role of
a proton shuttle in the reaction, moving protons from either 3-
hexyne or another equivalent of −NMe2 to the imine product.
Prompted by these dual pathways, we hypothesized that
secondary amines bearing more acidic α-hydrogens would be a
more efficient source of hydrogen than 3-hexyne. In fact,
reaction of 3-hexyne with N-benzylaniline (4) and azobenzene
resulted in near quantitative (91% based on PhNNPh)
formation of 3 (eq 4), along with significant formation of N-
phenylaldimine dehydrogenated byproduct 5 (45%)indicat-
ing that β-H abstraction from more reactive Ti-amides can
occur at rates competitive with those of 3-hexyne deprotona-
tion.
Following the success of N-benzylaniline in the nitrene-
coupled transfer hydrogenation reaction, we also investigated
simple azobenzene hydrogenation35,36 using 4 as a direct probe
of the efficiency of transfer hydrogenation via solely β-H
abstraction (eq 5; see Supporting Information for the full
proposed mechanism). In this case, good yield (36%) of
PhNH2 6 could be achieved with prolonged heating, although
the reaction was not as fast or efficient as those with 3-hexyne
as a hydrogen source. Satisfyingly, the reactions in eqs 4 and 5
allowed observation of the dehydrogenated byproduct 5:
previously, N-methylformimine and 2,3,4-hexatriene were not
detected, presumably due to their decomposition at elevated
temperature.
B
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(2) Kulinkovich, O. G.; Sviridov, S. V.; Vasilevski, D. A. Reaction of
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Ti II Alkyne Trimerization Catalysts in the Absence of Strong Metal
Reductants. Organometallics 2017, 36 (7), 1383−1390.
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Similar reactions catalyzed by other simple early transition
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Ta(NMe2)5 (Tables S1 and S2), were not as effective as
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the coordination environment and Lewis acidity of the metal.
In conclusion, we have discovered that TiII can be accessed
from a simple Ti diamide via β-H abstraction or alkyne
deprotonation, and these elementary steps can be incorporated
into a unique Ti-catalyzed nitrene-coupled transfer hydro-
genation reaction. An isotope labeling study indicates that
alkyne deprotonation appears more facile than β-H abstraction.
Although these catalytic reactions are likely not of practical
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chemistry of Ti,37,38 and chemical vapor deposition of
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.organomet.0c00577.
■
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Full experimental details (PDF)
AUTHOR INFORMATION
Corresponding Author
Ian A. Tonks − Department of Chemistry, University of
MinnesotaTwin Cities, Minneapolis, Minnesota 55455,
United States; orcid.org/0000-0001-8451-8875;
Email: itonks@umn.edu
■
(11) Kubiak, R.; Prochnow, I.; Doye, S. Titanium-Catalyzed
Hydroaminoalkylation of Alkenes by C-H Bond Activation at sp3
Centers in the α-Position to a Nitrogen Atom. Angew. Chem., Int. Ed.
2009, 48 (6), 1153−1156.
Authors
Adam J. Pearce − Department of Chemistry, University of
MinnesotaTwin Cities, Minneapolis, Minnesota 55455,
United States
Yukun Cheng − Department of Chemistry, University of
MinnesotaTwin Cities, Minneapolis, Minnesota 55455,
United States; orcid.org/0000-0002-2379-9404
Rachel J. Dunscomb − Department of Chemistry, University of
MinnesotaTwin Cities, Minneapolis, Minnesota 55455,
United States
(12) Eisenberger, P.; Ayinla, R. O.; Lauzon, J. M. P.; Schafer, L. L.
Tantalum-Amidate Complexes for the Hydroaminoalkylation of
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by C-H Activation of N-Methylanilines at Ambient Temperature.
Angew. Chem., Int. Ed. 2015, 54 (14), 4383−4387.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.organomet.0c00577
(14) Hill, J. E.; Profilet, R. D.; Fanwick, P. E.; Rothwell, I. P.
Synthesis, Structure, and Reactivity of Aryloxo(Imido)Titanium
Complexes. Angew. Chem., Int. Ed. Engl. 1990, 29 (6), 664−665.
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Author Contributions
†A.J.P. and Y.C. contributed equally.
Notes
The authors declare no competing financial interest.
(16) Gilbert, Z. W.; Hue, R. J.; Tonks, I. A. Catalytic Formal [2 +
2+1] Synthesis of Pyrroles from Alkynes and Diazenes via TiII/TiIV
redox Catalysis. Nat. Chem. 2016, 8 (1), 63−68.
ACKNOWLEDGMENTS
■
(17) Beaumier, E. P.; Ott, A. A.; Wen, X.; Davis-Gilbert, Z. W.;
Wheeler, T. A.; Topczewski, J. J.; Goodpaster, J. D.; Tonks, I. Ti-
Catalyzed Ring-Opening Oxidative Amination of Methylenecyclopro-
panes with Diazenes. Chem. Sci. 2020, 11 (27), 7204−7209.
(18) Heins, S. P.; Wolczanski, P. T.; Cundari, T. R.; MacMillan, S.
N. Redox Non-Innocence Permits Catalytic Nitrene Carbonylation by
(Dadi)Ti = NAd (Ad = Adamantyl). Chem. Sci. 2017, 8 (5), 3410−
3418.
Financial support was provided by the National Institutes of
Health (R35GM119457) and the Alfred P. Sloan Foundation
(I.A.T. is a 2017 Sloan Fellow). Instrumentation for the
University of Minnesota Chemistry NMR facility was
supported from a grant through the National Institutes of
Health (S10OD011952).
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