Mechanistic investigation of intramolecular aminoalkene and aminoalkyne hydroamination/cyclization catalyzed by highly electrophilic, tetravalent constrained geometry 4d and 5f complexes. Evidence for an M-N σ-bonded insertive pathway

Article abstract of DOI:10.1021/ja0675898

A mechanistic study of intramolecular hydroamination/cyclization catalyzed by tetravalent organoactinide and organozirconium complexes is presented. A series of selectively substituted constrained geometry complexes, (CGC)M(NR ₂)Cl (CGC = [Me

Full text of DOI:10.1021/ja0675898

Published on Web 04/19/2007
Mechanistic Investigation of Intramolecular Aminoalkene and
Aminoalkyne Hydroamination/Cyclization Catalyzed by Highly
Electrophilic, Tetravalent Constrained Geometry 4d and 5f
Complexes. Evidence for an M-N σ-Bonded Insertive Pathway
Bryan D. Stubbert and Tobin J. Marks*
Contribution from the Department of Chemistry, Northwestern UniVersity,
EVanston, Illinois 60208-3113
Received October 24, 2006; E-mail: t-marks@northwestern.edu
Abstract: A mechanistic study of intramolecular hydroamination/cyclization catalyzed by tetravalent
organoactinide and organozirconium complexes is presented. A series of selectively substituted constrained
geometry complexes, (CGC)M(NR2)Cl (CGC ) [Me2Si(η5-Me4C5)(tBuN)]2-; M ) Th, 1-Cl; U, 2-Cl; R )
SiMe3; M ) Zr, R ) Me, 3-Cl) and (CGC)An(NMe2)OAr (An ) Th, 1-OAr; An ) U, 2-OAr), has been
prepared via in situ protodeamination (complexes 1-2) or salt metathesis (3-Cl) in high purity and excellent
yield and is found to be active precatalysts for intramolecular primary and secondary aminoalkyne and
aminoalkene hydroamination/cyclization. Substrate reactivity trends, rate laws, and activation parameters
for cyclizations mediated by these complexes are virtually identical to those of more conventional (CGC)-
MR2 (M ) Th, R ) NMe2, 1; M ) U, R ) NMe2, 2; M ) Zr, R ) Me, 3), (Me2SiCp′′2)UBn2 (Cp′′ ) η5-Me4C5;
Bn ) CH2Ph, 4), Cp′2AnR2 (Cp′ ) η5-Me5C5; R ) CH2SiMe3; An ) Th, 5, U, 6), and analogous
organolanthanide complexes. Deuterium KIEs measured at 25 °C in C6D6 for aminoalkene D2NCH2C(CH3)2-
CH2CHCH2 (11-d2) with precatalysts 2 and 2-Cl indicate that kH/kD ) 3.3(5) and 2.6(4), respectively.
Together, the data provide strong evidence in these systems for turnover-limiting CsC insertion into an
MsN(H)R σ-bond in the transition state. Related complexes (Me2SiCp′′2)U(Bn)(Cl) (4-Cl) and Cp′2An(R)-
(Cl) (R ) CH2(SiMe3); An ) Th, 5-Cl; An ) U, 6-Cl) are also found to be effective precatalysts for this
transformation. Additional arguments supporting MsN(H)R intermediates vs MdNR intermediates are
presented.
diastereoselectivities (>95%)1d and with enantioselectivities as
Introduction
high as 95%.4b Mechanistic experiments with rigorously trivalent
Hydroamination (HA), the atom-economical addition of an
NsH bond across a CsC unsaturation,1 is an important
synthetic methodology for regiospecific CsN bond formation,
a topic of considerable academic and industrial interest.2
Research on this transformation pervades the Periodic Table,1
with extensively studied organolanthanide-catalyzed intramo-
lecular HA/cyclization playing a prominent role,3,4 typically
displaying near-quantitative yields in addition to high regio- and
lanthanide (Ln) catalysts on intramolecular aminoalkene,3v,w
(3) (a) Motta, A.; Lanza, G.; Fragala, I. L.; Marks, T. J. Organometallics 2004,
23, 4097-4104. (b) Seyam, A. M.; Stubbert, B. D.; Jensen, T. R.;
O’Donnell, J. J., III; Stern, C. L.; Marks, T. J. Inorg. Chim. Acta 2004,
357, 4029-4035. (c) Ryu, J.-S.; Marks, T. J.; McDonald, F. E. J. Org.
Chem. 2004, 69, 1038-1052. (d) Hong, S.; Kawaoka, A. M.; Marks, T. J.
J. Am. Chem. Soc. 2003, 125, 15878-15892. (e) Hong, S.; Tian, S.; Metz,
M. V.; Marks, T. J. J. Am. Chem. Soc. 2003, 125, 14768-14783. (f) Ryu,
J.-S.; Li, G. Y.; Marks, T. J. J. Am. Chem. Soc. 2003, 125, 12584-12605.
(g) Hong, S.; Marks, T. J. J. Am. Chem. Soc. 2002, 124, 7886-7887. (h)
Ryu, J.-S.; Marks, T. J.; McDonald, F. E. Org. Lett. 2001, 3, 3091-3094.
(i) Arredondo, V. M.; Tian, S.; McDonald, F. E.; Marks, T. J. J. Am. Chem.
Soc. 1999, 121, 3633-3639. (j) Arredondo, V. M.; McDonald, F. E.; Marks,
T. J. Organometallics 1999, 18, 1949-1960. (k) Tian, S.; Arredondo, V.
M.; Stern, C. L.; Marks, T. J. Organometallics 1999, 18, 2568-2570. (l)
Arredondo, V. M.; McDonald, F. E.; Marks, T. J. J. Am. Chem. Soc. 1998,
120, 4871-4872. (m) Li, Y.; Marks, T. J. J. Am. Chem. Soc. 1998, 120,
1757-1771. (n) Roesky, P. W.; Stern, C. L.; Marks, T. J. Organometallics
1997, 16, 4705-4711. (o) Li, Y.; Marks, T. J. J. Am. Chem. Soc. 1996,
118, 9295-9306. (p) Li, Y.; Marks, T. J. Organometallics 1996, 15, 3770-
3772. (q) Li, Y.; Marks, T. J. J. Am. Chem. Soc. 1996, 118, 707-708. (r)
Giardello, M. A.; Conticello, V. P.; Brard, L.; Gagne´, M. R.; Marks, T. J.
J. Am. Chem. Soc. 1994, 116, 10241-10254. (s) Giardello, M. A.;
Conticello, V. P.; Brard, L.; Sabat, M.; Rheingold, A. L.; Stern, C. L.;
Marks, T. J. J. Am. Chem. Soc. 1994, 116, 10212-10240. (t) Li, Y.; Fu,
P.-F.; Marks, T. J. Organometallics 1994, 13, 439-440. (u) Gagne´, M.
R.; Brard, L.; Conticello, V. P.; Giardello, M. A.; Stern, C. L.; Marks, T.
J. J. Am. Chem. Soc. 1992, 11, 2003-2005. (v) Gagne´, M. R.; Stern, C.
L.; Marks, T. J. J. Am. Chem. Soc. 1992, 114, 275-94. (w) Gagne´, M. R.;
Marks, T. J. J. Am. Chem. Soc. 1989, 111, 4108-9. (x) Motta, A.; Lanza,
G.; Fragala, I. L.; Marks, T. J. Organometallics 2006, 25, 5533-5539.
(1) For general hydroamination reviews, see: (a) Odom, A. L. Dalton Trans.
2005, 225-233. (b) Hultzsch, K. C. AdV. Synth. Catal. 2005, 347, 367-
391. (c) Hultzsch, K. C.; Gribkov, D. V.; Hampel, F. J. Organomet. Chem.
2005, 690, 4441-4452. (d) Hong, S.; Marks, T. J. Acc. Chem. Res. 2004,
37, 673-686. (e) Doye, S. Synlett 2004, 1653-1672. (f) Beller, M.; Tillack,
A.; Seayad, J. In Transition Metals for Organic Synthesis, 2nd ed.; Beller,
M., Bolm, C., Eds.; Wiley-VCH: Weinheim, 2004; pp 91-141. (g) Roesky,
P. W.; Mueller, T. E. Angew. Chem., Int. Ed. 2003, 42, 2708-2710. (h)
Pohlki, F.; Doye, S. Chem. Soc. ReV. 2003, 32, 104-114. (i) Bytschkov,
I.; Doye, S. Eur. J. Org. Chem. 2003, 2003, 935-946. (j) Seayad, J.; Tillack,
A.; Hartung, C. G.; Beller, M. AdV. Synth. Catal. 2002, 344, 795-813. (k)
Togni, A. In Catalytic Heterofunctionalization; Togni, A., Gruetzmacher,
H., Eds.; Wiley-VCH: New York, 2001; pp 91-141. (l) Nobis, M.;
Drieâen-Holscher, B. Angew. Chem., Int. Ed. 2001, 40, 3983-3985. (m)
Eisen, M. S.; Straub, T.; Haskel, A. J. Alloys Compd. 1998, 271-273,
116-122. (n) Mueller, T. E.; Beller, M. Chem. ReV. 1998, 98, 675-703.
(2) For general C-N bond-formation references, see: (a) Beller, M.; Seayad,
J.; Tillack, A.; Jiao, H. Angew. Chem., Int. Ed. 2004, 43, 3368-3398. (b)
Hartwig, J. F. Science 2002, 297, 1653-1654. (c) Beller, M.; Riermeier,
T. H. Transition Met. Org. Synth. 1998, 1, 184-194. (d) Hegedus, L. S.
Angew. Chem., Int. Ed. Engl. 1988, 27, 1113-1126.
9
10.1021/ja0675898 CCC: $37.00 © 2007 American Chemical Society
J. AM. CHEM. SOC. 2007, 129, 6149-6167
6149

A R T I C L E S
Stubbert and Marks
Scheme 1. Proposed σ-Bond Insertive Mechanism for Intramolecular Aminoalkene and Aminoalkyne HA/Cyclization Mediated by Trivalent
Organolanthanide Complexesa
a The pathway proposed for L2Ln3+-catalyzed intermolecular HA is similar, also proceeding through an L2Ln-N(H)R σ-bonded species, leading to a
transition state analogous to A (see ref 1d).
aminoalkyne,3m,o-q,t aminoallene,3i,j,l internal olefin,3c,h and
aminodiene3d,g HA/cyclization generally argue for turnover-
limiting CdC/CtC insertion into an L2LnsN σ-bond (Scheme
1). The observed rate law (ν ∼ [Ln]1[substrate]0), moderate ∆H‡,
and large negative ∆S‡ are consistent with a highly ordered,
polar A-like transition state,1d as are DFT calculations implicat-
ing an L2Ln[N(H)R](H2NR) catalyst resting state and A-like
species.3a,x,5
While growing interest in intramolecular aminoalkene6 and
aminoalkyne7 HA/cyclization mediated by charge-neutral group
4 precatalysts has led to innovative catalyst design, many
mechanistic details are not entirely understood. The pathway
most often invoked is closely related to that originally proposed
in the pioneering work of Bergman and co-workers (Scheme
2) for intermolecular alkyne (and allene) HA with bulky,
primary ArNH2 substrates, mediated by Cp2ZrR2 (R ) Me,
N(H)Ar) or Cp2ZrdNAr(THF) complexes at elevated temper-
atures.8 This pathway involves a rapid pre-equilibrium (step (i),
Scheme 2) between Cp2Zr[N(H)Ar]2 and Cp2ZrdNAr (B) +
H2NAr species, followed by turnover-limiting [2 + 2]
RCtCR′ cycloaddition (step (ii), Scheme 2), in agreement with
the observed rate law (ν ∼ [Zr]1[alkyne]1[amine]-1). Similar
kinetic studies on Cp′2AnMe2-catalyzed intermolecular addition
of bulky and unhindered primary aliphatic amines to terminal
alkynes led Eisen and co-workers to propose a similar pathway
for Cp′2An< catalysts with rapid, irreversible [2 + 2]
RCtCR′ cycloaddition.9 Interestingly, neither Cp2Zr< nor
(4) For additional examples of group 3 and lanthanide catalyzed intramolecular
HA, see: (a) Bambirra, S.; Tsurugi, H.; van Leusen, D.; Hessen, B. Dalton
Trans. 2006, 1157-1161. (b) Gribkov, D. V.; Hultzsch, K. C.; Hampel, F.
J. Am. Chem. Soc. 2006, 128, 3748-3759. (c) Panda, T. K.; Zulys, A.;
Gamer, M. T.; Roesky, P. W. Organometallics 2005, 24, 2197-2202. (d)
Collin, J.; Daran, J.-C.; Jacquet, O.; Schulz, E.; Trifonov, A. Chem.sEur.
J. 2005, 11, 3455-3462. (e) Kim, J. Y.; Livinghouse, T. Org. Lett. 2005,
7, 4391-4393. (f) Kim, J. Y.; Livinghouse, T. Org. Lett. 2005, 7, 1737-
1739. (g) Molander, G. A.; Hasegawa, H. Heterocycles 2004, 64, 467-
474. (h) Lauterwasser, F.; Hayes, P. G.; Brase, S.; Piers, W. E.; Schafer,
L. L. Organometallics 2004, 23, 2234-2237. (i) Hultzsch, K. C.; Hampel,
F.; Wagner, T. Organometallics 2004, 23, 2601-2612. (j) O’Shaughnessy,
P. N.; Gillespie, K. M.; Knight, P. D.; Munslow, I. J.; Scott, P. Dalton
Trans. 2004, 2251-2256. (k) O’Shaughnessy, P. N.; Scott, P. Tetrahe-
dron: Asymmetry 2003, 14, 1979-1983. (l) O’Shaughnessy, P. N.; Knight,
P. D.; Morton, C.; Gillespie, K. M.; Scott, P. Chem. Commun. 2003, 1770-
1771. (m) Kim, Y. K.; Livinghouse, T.; Horino, Y. J. Am. Chem. Soc.
2003, 125, 9560-9561. (n) Molander, G. A.; Pack, S. K. Tetrahedron 2003,
59, 10581-10591. (o) Molander, G. A.; Pack, S. K. J. Org. Chem. 2003,
68, 9214-9220. (p) Kim, Y. K.; Livinghouse, T. Angew. Chem., Int. Ed.
2002, 41, 3645-3647. (q) Bu¨rgstein, M. R.; Berberich, H.; Roesky, P. W.
Chem.sEur. J. 2001, 7, 3078-3085. (r) Kim, Y. K.; Livinghouse, T.;
Bercaw, J. E. Tetrahedron Lett. 2001, 42, 2933-2935. (s) Molander, G.
A.; Dowdy, E. D. J. Org. Chem. 1999, 64, 6515-6517. (t) Molander, G.
A.; Dowdy, E. D. J. Org. Chem. 1998, 63, 8983-8988.
(5) A slightly modified pathway arguing in favor of turnover-limiting
heterocycle protonolysis in intramolecular aminoallene and aminodiene HA/
cyclization was proposed from DFT calculations. (a) Tobisch, S. Chem.s
Eur. J. 2006, 12, 2520-2531. (b) Tobisch, S. J. Am. Chem. Soc. 2005,
127, 11979-11988.
(6) (a) Wood, M. C.; Leitch, D. C.; Yeung, C. S.; Kozak, J. A.; Schafer, L. L.
Angew. Chem., Int. Ed. 2007, 46, 354-358. (b) Thomson, R. K.; Bexrud,
J. A.; Schafer, L. L. Organometallics 2006, 25, 4069-4071. (c) Mueller,
C.; Loos, C.; Schulenberg, N.; Doye, S. Eur. J. Org. Chem. 2006, 2499-
2503. (d) Kim, H.; Lee, P. H.; Livinghouse, T. Chem. Commun. 2005,
5205-5207. (e) Bexrud, J. A.; Beard, J. D.; Leitch, D. C.; Schafer, L. L.
Org. Lett. 2005, 7, 1959-1962.
(7) (a) Heutling, A.; Pohlki, F.; Bytschkov, I.; Doye, S. Angew. Chem., Int.
Ed. 2005, 44, 2951-2954. (b) Ackermann, L.; Bergman, R. G.; Loy, R.
N. J. Am. Chem. Soc. 2003, 125, 11956-11963. (c) Li, C.; Thompson, R.
K.; Gillon, B.; Patrick, B. O.; Schafer, L. L. Chem. Commun. 2003, 2462-
2463. (d) Ackermann, L.; Bergman, R. G. Org. Lett. 2002, 4, 1475-1478.
(e) Bytschkov, I.; Doye, S. Tetrahedron Lett. 2002, 43, 3715-3718. (f)
McGrane, P. L.; Livinghouse, T. J. Org. Chem. 1992, 57, 1323-1324. (g)
McGrane, P. L.; Jensen, M.; Livinghouse, T. J. Am. Chem. Soc. 1992, 114,
5459-5460.
(8) (a) Baranger, A. M.; Walsh, P. J.; Bergman, R. G. J. Am. Chem. Soc. 1993,
115, 2753-2763. (b) Walsh, P. J.; Baranger, A. M.; Bergman, R. G. J.
Am. Chem. Soc. 1992, 114, 1708-1719.
9
6150 J. AM. CHEM. SOC. VOL. 129, NO. 19, 2007

Evidence for an M
−N
σ
-Bonded Insertive Pathway
A R T I C L E S
Scheme 2. Proposed [2 + 2] Cycloaddition Mechanistic Pathway Proceeding through a Cp2ZrdNAr Intermediate B in Intermolecular Alkyne
HA with Bulky (Aromatic) Aminesa
a A closely related pathway is proposed for Cp′2An<-catalyzed alkyne HA (see refs 8, 9 and eq 10).
of substrate structure-reactivity patterns, kinetic data paralleling
organo-4f-element catalysis, and the empirical rate law
ν ∼ [(CGC)An<]1[amine]0, a “Ln-like” mechanistic scenario
proceeding via a tetravalent AnsN(H)R σ-bonded species (C)
was tentatively suggested (Scheme 3). However, while this
pathway is plausible for secondary aminoalkenes, cyclizations
proceeding through AndNR species cannot a priori be excluded
for primary aminoalkenes. These observations along with the
paucity of mechanistic information on intramolecular HA/
cyclization processes mediated by tetravalent group 4 metal
centers and known group 4 vs An4+ MsN bond polarity
differences prompted a mechanistic investigation. Herein we
report evidence for turnover-limiting CdC/CtC insertion at
AnsN(H)R species, supported by results with a series of
monosubstituted (CGC)An(NR2)X complexes (X ) nonlabile
ligand) that rapidly and regioselectively mediate intramolecular
primary and secondary aminoalkene and aminoalkyne HA/
cyclization. Selective substitution of a protonolytically nonlabile
X ligand for a protonolytically labile amide generates catalysts
with only a single nondative σ-bonded substrate moiety, unlikely
to support AndNR formation for a comparable energetic cost.
Extension to analogous (CGC)Zr<-catalyzed HA/cyclization
Cp′2An< appear to be active catalysts for primary amine
additions in less exothermic1 intermolecular alkene HA.
In contrast to the above findings, more active cationic
U(NEt2)3+BPh4- displays kinetic behavior similar to Cp′2An<-
and Cp2Zr<-catalyzed intermolecular terminal alkyne HA but
effects secondary HNEt2 addition to Me3SiCtCH,9a arguing
against an AndNR intermediate (vide infra). Moreover, cationic
organozirconium and organotitanium complexes effect related
intramolecular aminoalkene HA/cyclizations, with the reported
scope limited exclusiVely to secondary aminoalkenes, offering
no obvious routes to L2MdNR species.10
In a companion contribution, we report the rapid and
regioselective intramolecular HA/cyclization of primary and
secondary amines having diverse tethered CsC unsaturations,
mediated by a new series of constrained geometry organoac-
tinide complexes (CGC)An(NMe2)2 (An ) Th, 1; An ) U, 2).11
The scope of CsC unsaturations was explored in depth for
terminal and disubstituted alkene, alkyne, allene, and diene
substrates, revealing aminoalkene and aminoalkyne turnover
frequencies comparable to those of organolanthanide catalysts
and exceeding those of organo-group 4 catalysts.11b On the basis
(9) (a) Wang, J.; Dash, A. K.; Kapon, M.; Berthet, J.-C.; Ephritikhine, M.;
Eisen, M. S. Chem.sEur. J. 2002, 8, 5384-5396. (b) Straub, T.; Haskel,
A.; Neyroud, T. G.; Kapon, M.; Botoshansky, M.; Eisen, M. S. Organo-
metallics 2001, 20, 5017-5035. (c) Haskel, A.; Straub, T.; Eisen, M. S.
Organometallics 1996, 15, 3773-3775.
(10) (a) Gribkov, D. V.; Hultzsch, K. C. Angew. Chem., Int. Ed. 2004, 43, 5542-
5546. (b) Knight, P. D.; Munslow, I.; O’Shaughnessy, P. N.; Scott, P. Chem.
Commun. 2004, 894-895.
(11) (a) Stubbert, B. D.; Stern, C. L.; Marks, T. J. Organometallics 2003, 22,
4836-4838. (b) Stubbert, B. D.; Marks, T. J. J. Am. Chem. Soc. 2007,
129(14), 4253-4271.
9
J. AM. CHEM. SOC. VOL. 129, NO. 19, 2007 6151

A R T I C L E S
Stubbert and Marks
Scheme 3. Proposed σ-Bond Insertive Mechanism for (CGC)M<-Catalyzed Intramolecular HA/Cyclization (M ) Zr, Th, U) of Terminal and
Disubstituted Aminoalkenes, Aminoalkynes, Aminoallenes, and Aminodienesa
a When X ) NR2, two substrate molecules enter the catalytic cycle and two HNR2 are evolved during precatalyst activation (see ref 11 for additional
details regarding the empirical rate law determination).
Chart 1
reactions yields similar results. In most cases, the (CGC)M-
(NR2)X complexes effect HA reactions more rapidly than the
corresponding (CGC)MR2 complexes, further supporting the
Scheme 3 pathway.
Results
In this section we discuss the synthesis and structural
characterization of a series of selectively substituted, electro-
philic, tetravalent actinide and group 4 (CGC)M(NR2)X com-
plexes and mechanistic studies of representative primary and
secondary aminoalkene and aminoalkyne intramolecular HA/
cyclizations mediated by these complexes. Effects of catalyst
substitution, metal ion, and ancillary ligation are presented along
with relevant kinetic parameters and deuterium KIE data. It will
be seen that these chloride- and aryloxide-substituted complexes
are highly active HA/cyclization catalysts that display kinetic
and mechanistic signatures inconsistent with MdNR species
in the catalytic cycle. A mechanistic pathway proceeding through
an MsN σ-bonded species is proposed based on results
presented herein.
Synthesis and Characterization of Chloride- and Arylox-
ide-Substituted (CGC)M(NR2)X Complexes. (CGC)An-
[N(SiMe3)2]Cl complexes 1-Cl and 2-Cl are accessible in
excellent yield and high purity from the corresponding AnCl4
reagents via in situ generation of the tris(hexamethyldisilazido)-
actinide chlorides, An[N(SiMe3)2]3Cl,12 followed by protodeam-
ination with diprotic H2CGC,13 evolving hexamethyldisilazane
over 16 h at 70 °C (Scheme 4; Chart 1). Owing to unfavorable
steric interactions that preclude An[N(SiMe3)2]4 formation, the
desired complexes are obtained without (CGC)An[N(SiMe3)2]2
contamination. The analogous group 4 complex (CGC)Zr-
(12) (a) Simpson, S. J.; Turner, H. W.; Andersen, R. A. Inorg. Chem. 1981, 20,
2991-2995. (b) Turner, H. W.; Simpson, S. J.; Andersen, R. A. J. Am.
Chem. Soc. 1979, 101, 2782. (c) Turner, H. W.; Andersen, R. A.; Zalkin,
A.; Templeton, D. H. Inorg. Chem. 1979, 18, 1221-1224. (d) Bradley, D.
C.; Ghotra, J. S.; Hart, F. A. Inorg. Nucl. Chem. 1974, 10, 209-211.
(13) Shapiro, P. J.; Schaefer, W. P.; Labinger, J. A.; Bercaw, J. E.; Cotter, W.
D. J. Am. Chem. Soc. 1994, 116, 4623-40.
9
6152 J. AM. CHEM. SOC. VOL. 129, NO. 19, 2007

Evidence for an M
−N
σ
-Bonded Insertive Pathway
A R T I C L E S
Scheme 4. Syntheses of Constrained Geometry Organoactinide and Organozirconium Complexes 1-Cl, 2-Cl, 3-Cl, 1-OAr, and 2-OAr
(NMe2)(Cl) 3-Cl was obtained by traditional salt metathesis from
(CGC)ZrCl2 and LiNMe2 (Scheme 4; Chart 1). No evidence
for amide-halide disproportion is observed by 1H NMR
spectroscopy at 25 °C over a period of days for any of the
chloride-substituted complexes prepared in this study. Solid-
state structures were defined by single-crystal X-ray diffraction,
indicating that 1-Cl is a bis(µ-chloro) dimer in the solid state,
while 2-Cl and 3-Cl are monomeric (Tables 1 and 2, Figure
1a-c; vide infra).
Aryloxide complexes (CGC)An(NMe2)OAr, 1-OAr and
2-OAr, are cleanly obtained by protodeamination of (CGC)-
An(NMe2)2 complex 1 or 2 with an excess of sterically hindered
2,6-di-tert-butylphenol, ArOH (Scheme 4; Chart 1). In the case
of An ) U, treatment of 2 with 1.8 equiv of ArOH leads to
exclusive formation of 2-OAr, leaving 0.8 equiv of unreacted
ArOH. Initial 1H NMR screening experiments indicate complete
consumption of 2 within 30 min of dissolution in benzene-d6
and negligible interaction between the paramagnetic U4+ ion
and unreacted ArOH (as judged by negligible isotropic shifts
of the resonances) up to temperatures of 90 °C. Similar
experiments carried out with Th complex 1 and 1.2 equiv of
ArOH to generate 1-OAr indicate further reaction and complete
consumption of excess ArOH within 60 min at 25 °C. In
preparative scale syntheses, the (CGC)Th(OAr)2 byproduct is
easily removed by filtration from concentrated pentane solu-
tions of the otherwise pure monoaryloxide complex. When in
situ generated 1-OAr containing 5-10% (CGC)Th(OAr)2 is
employed in catalytic HA experiments, results are identical
to those obtained with isolated 1-OAr. Complex 1-OAr
was also analyzed via single-crystal X-ray diffraction and shown
to be monomeric in the solid state (Tables 1 and 2, Figure 1d).
Table 1. Selected Bond Distances (Å) and Angles (deg) for
[(CGC)Th[N(SiMe3)2](µ-Cl)]2 (1-Cl), (CGC)U[N(SiMe3)2]Cl (2-Cl),
(CGC)Zr(NMe2)Cl (3-Cl), and (CGC)Th(NMe2)OAr (1-OAr)a
1-Cl
2-Cl
3-Cl
1-OAr
Catalytic Intramolecular Hydroamination/Cyclization Ex-
periments. In this section, results of catalytic intramolecular
HA/cyclization of representative aminoalkyne and aminoalkene
substrates, mediated by precatalysts (CGC)An(NMe2)2 (An )
Th, 1; An ) U, 2),11 [(CGC)Th(NR2)(µ-Cl)]2 (R ) SiMe3,
1-Cl),14 (CGC)M(NR2)Cl (M ) U, R ) SiMe3, 2-Cl; M ) Zr,
R ) Me, 3-Cl),14 (CGC)ZrMe2 (3),15 (CGC)An(NMe2)OAr
(OAr ) 2,6-di-tert-Bu-phenoxide; An ) Th, 1-OAr; An ) U,
Cp(cent)-M-N1 91.7
Cp(cent)-M-X 94.8/157.8
Cp(cent)-M-N2 108.8
93.1
108.1
122.1
101.1
131.9
104.4
90.4
136.6
106.9
N1-M-X
N1-M-N2
N2-M-X
107.7(1)
100.52(7) 115.10(7) 115.9(2)
123.8(1) 104.7(1) 102.0(2)
106.67(8) 104.06(8) 100.9(2)
110.8(2)
133.6(1)
Cp(cent)-M
M-N1
2.53
2.335(5)
2.334(5)
2.41
2.223(3)
2.257(3)
2.30
2.077(2)
2.078(3)
2.55
2.293(6)
2.252(6)
2.258(5)
M-N2
M-X
2.883(2)/2.964(2) 2.6124(9) 2.437(1)
(14) See Supporting Information for full details.
(15) Carpenetti, D. W.; Kloppenburg, L.; Kupec, J. T.; Petersen, J. L.
Organometallics 1996, 15, 1572-1581.
a See Supporting Information for complete listings (Cp(cent) ) Me4C5
ring centroid; X ) Cl or OAr).
9
J. AM. CHEM. SOC. VOL. 129, NO. 19, 2007 6153

A R T I C L E S
Stubbert and Marks
Table 2. Catalytic Data for the Intramolecular HA/Cyclization of Representative Aminoalkyne Substrates 7 and 9 Mediated by the Indicated
Actinide and Group 4 Complexes (See Supporting Information for Detailed Reaction Conditions)
1
1
a Identified by H NMR spectroscopy and GC/MS. b R ) SiMe3. c Determined in situ by H NMR spectroscopy. All yields g 95%. d Reference 11b.
e Isolated product from thermally induced 1,3-sigmatropic shift, N-(trimethylsilyl)-2-exo-methylene-pyrrolidine (see ref 19). f Typical reaction conditions:
2-11 mM [catalyst], 200 mM [aminoalkyne], 5-12 mM Si(p-tolyl)4 internal standard. Nt determined by least-squares analysis of linear plots of normalized
[substrate]/[catalyst] vs time over g3t1/2. See Supporting Information for details.
2-OAr),14 Me2SiCp′′2U(CH2Ph)2 (4),16 Me2SiCp′′2U(CH2Ph)-
Cl (4-Cl),16 Cp′2An(CH2SiMe3)2 (An ) Th, 5; An ) U, 6),17
and Cp′2An(CH2SiMe3)Cl (An ) Th, 5-Cl; An ) U, 6-Cl),17
are presented. Primary, N-unprotected substrates bearing
CtC11b and CdC11b,18 unsaturations are presented first, followed
by results with N-methyl substituted secondary amine substrates.
bulkier aryloxide-substituted 1-OAr (Nt ) 37 h-1; Table 2, entry
3). Smaller ionic radius (CGC)U< derivatives display a similar
trend, with 2-Cl mediating 7 f 8 more rapidly than 2-OAr (Nt
) 280 h-1 (2-Cl) and 52 h-1 (2-OAr) at 25 °C; Table 2, entries
5, 6). This conversion becomes less rapid as ancillary ligation
becomes less open, requiring mild heating to achieve moderate
Nt values. Note that no difference in reactivity is observed
between unaltered 4 and “substituted” 4-Cl (Nt ) 10 h-1 at 60
°C; Table 2, entries 7, 8). More sterically congested Cp′2An-
(R)Cl complexes 5-Cl and 6-Cl also mediate this transformation,
although catalytic activities are considerably lower than those
of their Cp′2AnR2 congeners (Nt ) 190 h-1 (5) and 1.2 h-1 at
60 °C (5-Cl); Nt ) 16 h-1 (6) and 0.4 h-1 (6-Cl) at 60 °C;
Table 2, entries 9-12).19 Isolation of volatiles following
complete 7 f 8 conversion with 5-Cl or 6-Cl and subsequent
Primary Aminoalkyne Hydroamination. Intramolecular
aminoalkyne HA/cyclization is effectively mediated by bisamido
as well as “substituted” chloroamido and aryloxoamido com-
plexes 1-6. In some cases, the substituted complexes promote
7 f 8 and 9 f 10 cyclizations with far greater catalytic
efficiency than the unsubstituted congeners. For example, 7 f
8 conversion mediated by 1-Cl proceeds at a rate more than
double that mediated by 1 at 25 °C (Nt ) 200 h-1 (1-Cl) vs 82
h-1 (1); Table 2, entries 1, 2) and with a 5× greater rate vs
(19) Isolated as the exo-methylene product from thermally-induced 1,3-
sigmatropic shift (-SiMe3 migration to N; see also ref 3p).
(16) Schnabel, R. C.; Scott, B. L.; Smith, W. H.; Burns, C. J. J. Organomet.
Chem. 1999, 591, 14-23.
(17) Fagan, P. J.; Manriquez, J. M.; Maatta, E. A.; Seyam, A. M.; Marks, T. J.
J. Am. Chem. Soc. 1981, 103, 6650-6667.
(18) (a) Tamaru, Y.; Hojo, M.; Higashimura, H.; Yoshida, Z. J. Am. Chem.
Soc. 1988, 110, 3994-4002. (b) Smith, J. K.; Bergbreiter, D. E.; Newcomb,
M. J. Org. Chem. 1985, 50, 4549-4553.
9
6154 J. AM. CHEM. SOC. VOL. 129, NO. 19, 2007

Evidence for an M
−N
σ
-Bonded Insertive Pathway
A R T I C L E S
Figure 1. ORTEP depictions of solid-state structures of the following precatalysts at -120 °C (a) dimeric [(CGC)Th[N(SiMe3)2](µ-Cl)]2 (1-Cl), (b)
(CGC)U[N(SiMe3)2]Cl (2-Cl), (c) (CGC)Zr(NMe2)Cl (3-Cl), and (d) (CGC)Th(NMe2)OAr (1-OAr; OAr ) 2,6-tBu2C6H3). Thermal ellipsoids are drawn at
the 50% probability level. See Table 1, Charts 1-4, and Supporting Information for complete structural data.
GC/MS and 1H NMR spectroscopic analyses provide no
evidence for formation of free HCp′ (or its derivatives) during
catalytic turnover.
for HA/cyclization 9 f 10 at 25 °C (M ) Th, U) or 60 °C (M
) Zr) in C6D6.
Intramolecular aminoalkyne HA/cyclizations 7 f 8 and 9
f 10 are efficient when catalyzed by (CGC)Zr< complexes 3
and 3-Cl, although moderate heating is required to obtain
activities comparable to the larger (CGC)An< complexes (Table
2). More reactive Me3Si-substituted 7 is converted to exocyclic
imine 8 with a markedly enhanced rate (ca. 100 ×) when
mediated by 3-Cl vs 3 (Nt ) 2.2 h-1 at 25 °C (3-Cl) vs 0.2 h-1
at 60 °C (3); Table 2, entries 13, 14). Catalytic conversion of
Me-substituted aminoalkyne 9 proceeds with a similar although
less pronounced 3-Cl vs 3 rate effect; i.e., a ca. 3× increase in
activity is observed for 3-Cl (Nt ) 0.7 h-1 (3-Cl) vs 0.2 h-1
(3) at 60 °C; Table 2, entries 21, 22). These systems also obey
the rate law ν ∼ [L2M<]1[amine]0 with competitive binding/
product inhibition of catalytic turnover sometimes observed at
high [product]. Eyring and Arrhenius analyses20 for 7 f 8
mediated by 3-Cl provide direct comparison to L2An< and L2-
Aminoalkyne transformation 9 f 10 is also mediated by the
present complexes (Table 2). Again, complex 1-Cl exhibits
enhanced activity vs 1 and 1-OAr (Nt ) 7.2 h-1 (1-Cl) vs 2.2
h-1 (1) and 0.5 h-1 (1-OAr) at 25 °C; Table 1, entries 15-17).
The (CGC)U<-catalyzed intramolecular HA/cyclization of 9 is
also efficient at 25 °C, with efficiencies 2 > 2-OAr > 2-Cl (Nt
) 170 h-1 (2), 7.2 h-1 (2-OAr), 2.9 h-1 (2-Cl); Table 2, entries
18-20). These systems obey the rate law ν ∼ [L2M<]1[amine]0
with competitive binding/product inhibition of catalytic turnover
sometimes observed at high product concentrations. Eyring and
Arrhenius analyses20 for 9 f 10 yield ∆H‡ ) 16(3) kcal/mol,
∆S‡ ) -18(9) eu, and Ea ) 17(3) kcal/mol when mediated by
2-Cl from 24.9 °C to 64.8 °C with well-behaved kinetics (Figure
2). Furthermore, in situ determination of the solution magnetic
moment of 2-Cl by the Evans’ method21 in bezene-d6 confirms
that µeff for (CGC)U< complex 2-Cl prior to activation with
substrate 9 is identical to that of the major paramagnetic species
present immediately following addition of 9, as well as during
and after complete conversion to 10 under typical HA conditions
at 25 °C. Note that (CGC)MCl2 complexes 1-Cl2 (M ) Th),11
2-Cl2 (M ) U),11 and 3-Cl2 (M ) Zr)15 are not active catalysts
Ln- catalysts, affording ∆H‡ ) 11(2) kcal/mol, ∆S‡
)
-35(7) eu, and Ea ) 12(2) kcal/mol from 24.8 °C to 67.3 °C
displaying well-behaved kinetics (Figure 3).
Primary Aminoalkene Hydroamination. Intramolecular
aminoalkene HA/cyclization of representative substrate 11 is
effectively mediated by both “substituted” and unsubstituted
bisamido complexes 1-3. Comparison between Th complexes
shows decreased activity for 1-Cl vs 1 at 25 °C (Nt ) 3.3 h-1
(1-Cl) vs 15 h-1 (1); Table 3, entries 1, 2), although dimeric
(20) Espenson, J. H. Chemical Kinetics and Reaction Mechanisms, 2nd ed.;
McGraw-Hill, Inc.: New York, 1995.
(21) (a) Schubert, E. M. J. Chem. Educ. 1992, 69, 62. (b) Evans, D. F. J. Chem.
Soc. 1959, 2003-2005.
9
J. AM. CHEM. SOC. VOL. 129, NO. 19, 2007 6155

A R T I C L E S
Stubbert and Marks
Figure 2. (a) Eyring plot for conversion 9 f 10 catalyzed by (CGC)U[N(SiMe3)2]Cl (2-Cl) from 24.9 to 64.8 °C in C6D6 (∆H‡ ) 16(3) kcal/mol, ∆S‡ )
-18(9) eu). (b) Arrhenius plot for conversion 9 f 10 catalyzed by 2-Cl over a 40 °C range in C6D6 (Ea ) 17(3) kcal/mol). (c) Representative kinetic plot
for conversion 9 f 10 catalyzed by 2-Cl in C6D6 at 40 °C. (d) Representative kinetic plot for conversion 9 f 10 catalyzed by (CGC)U(NMe2)OAr (2-OAr)
at 25 °C in C6D6. Nt (and rate constants) determined by least-squares analysis of linear plots of normalized [substrate]/[catalyst] vs time over g3t1/2. Standard
reaction conditions were employed in all catalytic reactions. Deviation from linearity at high conversion is attributed to product inhibition. See the Supporting
Information and ref 11b for details.
1-Cl may remain intact and, therefore, sterically encumbered
during catalysis. Precatalyst 1-Cl′, generated by treatment of
1-Cl with (noncyclizable) neopentylamine at 25 °C in C6D6 for
24 h followed by removal of byproduct HN(SiMe3)2, exhibits
an identical Nt (vs 1-Cl) for cyclization 11 f 12 at 25 °C,
suggesting that the structure of 1-Cl in solution (monomer vs
dimer) does not change with a large amine excess. Aryloxide-
substituted 1-OAr and 2-OAr exhibit diminished reactivity with
moderate Nt at 60 °C (0.6 h-1 and 1.5 h-1, respectively; Table
3, entries 3, 6). Interestingly, complex 2-Cl promotes 11 f 12
cyclization with >2× the catalytic efficiency of 2 at 25 °C (Nt
) 6.2 h-1 vs 2.5 h-1; Table 3, entries 4, 5). This 2/2-Cl trend
maintains for 11-d2 f 12-d2, where deuterium KIEs are
significant at 25 °C, with kH/kD ) 3.3(5) and 2.6(4), respectively
(Nt ) 0.8 h-1 (2) and 2.4 h-1 (2-Cl) at 25 °C). Likewise,
organozirconium complex 3-Cl exhibits greater catalytic activity
than 3, although rates are considerably more sluggish than that
for the Th analogue (Nt ) 0.14 h-1 (3-Cl) vs 0.07 h-1 (3); Table
3, entries 7, 8). Although the (CGC)Zr< complexes exhibit
sluggish cyclization rates and require elevated reaction temper-
atures, no reactions other than precatalyst protonolysis and CH4/
HNMe2 evolution are observed by 1H NMR spectroscopy below
100 °C. Furthermore, neither (CGC)Zr<-mediated reaction
evidences an induction period consistent with a disproportion-
ation or equilibration process preceding catalytic turnover (vide
infra). These systems obey the rate law ν ∼ [L2M<]1[amine]0
with competitive binding/product inhibition of catalytic turnover
sometimes observed at high [product]. Eyring and Arrhenius
analyses20 for 11 f 12 yield ∆H‡ ) 10(3) kcal/mol, ∆S‡ )
-43(9) eu, and Ea ) 11(3) kcal/mol when mediated by 2-OAr
from 63 °C to 100 °C (Figure 4) with well-behaved kinetics.
Secondary Aminoalkene and Aminoalkyne Hydroamina-
tion. Intramolecular aminoalkene and aminoalkyne HA/cycliza-
tion of representative secondary amines 13 and 15 is effectively
mediated by unsubstituted and “substituted” complexes 1-3 and
1-3, 5-6, respectively. Chloride-substituted 3-Cl mediates
N-methylaminoalkene cyclization 13 f 14 significantly more
rapidly than 3, although considerably more sluggishly than the
more reactive chloride-substituted organoactinide complexes (Nt
) 0.1 h-1 (1-Cl) and 0.2 h-1 (2-Cl) at 60 °C vs 0.4 h-1 (3-Cl)
at 90 °C and 0.2 h-1 (3) at 120 °C; Table 4, entries 2, 5, 7-8).
Cyclization 13 f 14 catalyzed by 1-OAr or 2-OAr proceeds
more sluggishly, with comparable efficiencies observed at 120
°C (0.5 h-1; Table 4, entries 3, 6). Mediated by 1 or 2 in the
more polar 1:1 ortho-C6H4F2/C6D6 solvent mixture, this trans-
formation proceeds with considerably diminished catalytic
efficiency (>10× for 2), although catalyst decomposition via
F- abstraction may occur for 1 (An ) Th).22 Note that Nt values
for 13 f 14 differ little between the 1- and 2-catalyzed processes
and those catalyzed by the corresponding monochloro deriva-
tives (Table 4, entries 1-2, 4-5). As noted above, these systems
(22) Heating (CGC)Th(NMe2) 2 in a 1:1 ortho-C6H4F2/C6D6 solvent mixture to
60 °C in the absence of substrate leads to rapid decomposition of 1 and
formation of an uncharacterized product.
9
6156 J. AM. CHEM. SOC. VOL. 129, NO. 19, 2007

Evidence for an M
−N
σ
-Bonded Insertive Pathway
A R T I C L E S
Figure 3. (a) Eyring plot for conversion 7 f 8 catalyzed by (CGC)Zr(NMe2)Cl (3-Cl) from 24.8 °C to 67.3 °C in C6D6 (∆H‡ ) 11(2) kcal/mol, ∆S‡ )
-35(7) eu). (b) Arrhenius plot for 7 f 8 conversion catalyzed by 3-Cl over 42 °C in C6D6 (Ea ) 12(2) kcal/mol). (c) Representative kinetic plot for
conversion 7 f 8 catalyzed by 3-Cl in C6D6 at 25 °C. Nt (and rate constants) determined by least-squares analysis of linear plots of normalized [substrate]/
[catalyst] vs time over g3t1/2. Standard reaction conditions were employed in all catalytic reactions. Deviation from linearity at high conversion is attributed
to product inhibition. See the Supporting Information for details.
also obey the rate law ν ∼ [L2M<]1[amine]0 with competitive
binding/product inhibition of catalytic turnover sometimes
observed at high [product]. Eyring and Arrhenius analyses20 for
13 f 14 yield ∆H‡ ) 9(3) kcal/mol, ∆S‡ ) -48(6) eu, and Ea
) 10(3) kcal/mol when mediated by 1 from 60 °C to 110 °C
(Figure 4) with well-behaved kinetics.
N-methylaminoalkyne 15 is also converted to exocyclic
pyrrolidine 16 by (CGC)An<, (CGC)Zr<, and Cp′2An<
complexes, although with considerably less efficiency when
promoted by 3 (Nt ) 80 h-1 (1) and 120 h-1 (2) at 25 °C, vs Nt
) 0.3 h-1 (3) at 90 °C; Table 4, entries 9, 11, 13). Metallocenes
5 and 6 are also effective precatalysts for this cyclization, with
intermediate efficiencies far less than those for 1 and 2 but
considerably greater than that for 3 (Nt ) 7.4 h-1 (5) and 15
h-1 (6) at 90 °C; Table 4, entries 15, 16). Monoamidochloride
complexes 1-3 also mediate 15 f 16 conversion effectively,
although with marked reduction in efficiency (Nt ) 24 h-1 (1-
Cl) and 33 h-1 (2-Cl) at 60 °C, and 0.02 h-1 at 90 °C (3-Cl);
Table 4, entries 10, 12, 14).
Synthesis and Characterization of Monosubstituted
(CGC)M(NR2)X Complexes. Monosubstituted chloride and
aryloxide complexes 1-3 are obtained in excellent yield and
purity in a single step from known reagents (Scheme 4). Neutral,
monomeric tris(amido)actinide chlorides, An[N(SiMe3)2]3Cl,12
are obtained quantitatively in toluene without competing forma-
tion of tris(amido)actinide hydrides12a,b or of potentially inhibi-
tory, charged/solvated byproducts. Treatment in situ with
H2CGC13 cleanly affords chloroamido complexes 1-Cl and 2-Cl
in up to 85% isolated yield. Note that the enhanced Lewis acidity
of An[N(SiMe3)2]3Cl vs homoleptic Ln[N(SiMe3)2]3 complexes
(used in the synthesis of closely related (CGC)Ln-N(SiMe3)2
complexes; eq 1)3k leads to significant rate enhancements in
1-Cl and 2-Cl generation, requiring markedly lower reaction
temperatures and proceeding without periodic removal of
evolved HN(SiMe3)2 (Scheme 4). 1H NMR spectra of 1-Cl and
2-Cl recorded in noncoordinating solvents at 20-80 °C are
consistent with C1 symmetry in solution and evidence no
detectable ligand redistribution or dynamic equilibria on the
NMR time scale.
Discussion
In this section, the synthesis, structural characterization, and
hydroamination/cyclization catalytic characteristics of bisamido
and substituted, monoamido complexes 1-6 are first discussed.
Implications of these findings are then presented in the context
of plausible mechanistic pathways for actinide vs group 4
mediated intramolecular aminoalkene and aminoalkyne HA/
cyclizations.
9
J. AM. CHEM. SOC. VOL. 129, NO. 19, 2007 6157

A R T I C L E S
Stubbert and Marks
Figure 4. (a) Eyring plot for conversion 11 f 12 catalyzed by (CGC)U(NMe2)OAr (2-OAr) from 63 to 100 °C in C6D6 (∆H‡ ) 10(3) kcal/mol, ∆S‡ )
-43(9) eu). (b) Arrhenius plot for conversion 11 f 12 catalyzed by 2-OAr over a 40 °C range in C6D6 (Ea ) 11(3) kcal/mol). (c) Eyring plot for conversion
13 f 14 catalyzed by (CGC)Th(NMe2)2 (1) from 60 to 110 °C in C6D6 (∆H‡ ) 9(3) kcal/mol, ∆S‡ ) -48(6) eu). (d) Arrhenius plot for conversion 13 f
14 catalyzed by 1 over a 50 °C range in C6D6 (Ea ) 10(3) kcal/mol). Nt and rate constants determined by least-squares analysis of linear plots of normalized
[substrate]/[catalyst] vs time over g3t1/2. Standard reaction conditions were employed in all catalytic reactions. See the Supporting Information and ref 11b
for details.
Table 3. Catalytic Data for the Intramolecular HA/Cyclization 11 f 12 Mediated by the Indicated Actinide and Group 4 Complexes (See
Supporting Information for Reaction Conditions)
1
1
a Identified by H NMR spectroscopy and GC/MS. b R ) SiMe3. c Determined in situ by H NMR spectroscopy. All yields > 95%. d Reference 11b.
e Typical reaction conditions: 2-11 mM [catalyst], 200 mM [aminoalkene], 5-12 mM Si(p-tolyl)4 internal standard. Nt determined by least-squares analysis
of linear plots of normalized [substrate]/[catalyst] vs time over g3t1/2. See Supporting Information for details.
Furthermore, the known insolubility of (CGC)AnCl2 com-
plexes in low-polarity solvents11 and absence of 1-Cl/2-Cl-
derived precipitates over several days in C6D6 suggest that the
bulky -N(SiMe3)2 moiety affords sufficient kinetic stabilization
to prevent halide/amide redistribution.
Interestingly, subtle An4+ ionic radius differences (nine-
coordinate: Th4+ 1.09 Å vs U4+ 1.05 Å)23 apparently result in
Th complex 1-Cl crystallizing as a C2-symmetric bis(µ-chloro)
dimer (Figure 1a). Single crystals of 1-Cl (Table S1) contain
planar, diamond-shaped Th2(µ-Cl)2 cores with Th-Cl-Th′ and
Cl-Th-Cl′ angles of 113.66(5)° and 66.34(5)°, respectively,
and a large Th‚‚‚‚Th distance of 4.89(1) Å. The Cp(centroid)-
(23) Shannon, R. D. Acta Crystallogr. 1976, A32, 751-67.
9
6158 J. AM. CHEM. SOC. VOL. 129, NO. 19, 2007

Evidence for an M
−N
σ
-Bonded Insertive Pathway
A R T I C L E S
Table 4. Catalytic Data for the Intramolecular HA/Cyclization of Representative Secondary Aminoalkene 13 and Secondary Aminoalkyne 15
Mediated by the Indicated Actinide and Group 4 Complexes (See Supporting Information for Reaction Conditions)
1
1
a Identified by H NMR spectroscopy and GC/MS. b R ) SiMe3. c Determined in situ by H NMR spectroscopy. All yields g 95%. d Reference 11b.
e Typical reaction conditions: 2-11 mM [catalyst], 200 mM [substrate], 5-12 mM Si(p-tolyl)4 internal standard. Nt determined by least-squares analysis of
linear plots of normalized [substrate]/[catalyst] vs time over g3t1/2. See Supporting Information for details.
Th-N(tBu) angle of 91.7° compares well with that in 1 (91.3°)11
and 1-OAr (90.4°; vide infra), indicating significant steric
openness (Chart 2).11,24 The 2.334(5) Å Th-N(SiMe3)2 bond
distance in 1-Cl is considerably longer than the 2.27(1) Å and
2.252(6) Å Th-NMe2 distances in 1 (average) and 1-OAr,
respectively, but statistically comparable (<3σ) to Th-N(tBu)
distances in 1-Cl (2.335(5) Å), 1 (2.315(4) Å), and 1-OAr
(2.293(6) Å), reflecting the electron-withdrawing capa-
city of the -SiMe3 groups.25 Bridging Th-Cl distances of
2.883(2) Å and 2.964(2) Å in 1-Cl are quite similar to
those of 2.874(2) Å and 2.933(2) Å in [(CGC)Th(µ-Cl)2-
(Cl)Li(OEt2)2]2.24a The similar U4+ dimer [(N[CH2CH2N-
(SiMe3)]3)U(µ-Cl)]2 also displays a planar U2(µ-Cl)2 diamond
core with U-Cl-U′ and Cl-U-Cl′ angles of 104.51(9)° and
75.49(8)°, respectively (Chart 2).24c Monomeric (N[CH2CH2N-
(SiMe3)]3)UCl possesses a terminal U-Cl distance of 2.641(5)
Å, roughly 10% shorter than that in the corresponding
dimer.24b The solid-state structures (Table S1) of monomeric
2-Cl (Figure 1b) and 3-Cl (Figure 1c) also display steric
openness nearly identical to that in unsubstituted analogues 2
and 3. Cp(centroid)-M-N(tBu) angles of 91.7° (1-Cl), 93.1°
(2-Cl), and 101.1° (3-Cl) correlate with the metal ionic
radius,23 evidencing greater coordinative unsaturation with
increasing ion size. Also, note the comparatively short Th‚‚‚‚
C(20) distance of 3.18(1) Å in 1-Cl vs U‚‚‚‚C(20) of 3.53(1) Å
in 2-Cl, suggesting agostic Si-C(R) bond stabilization in the
larger Th complex.3k,26,27
Redistribution processes analogous to eq 2 are known to
occur, especially in complexes with larger actinide ions in open
ligation environments and in the absence of coordinating
Lewis bases.26,28 To probe the importance of complicating
(CGC)M(NR2)Cl redistribution processes during catalytic reac-
tions, aryloxide-substituted precatalysts 1-OAr and 2-OAr were
generated via protodeamination of 1 and 2 with ArOH (2,6-di-
tBu-phenol; Scheme 4). The disparity in An4+ ionic radii/
covalency is evident where organouranium complex 2-OAr does
not undergo reaction with excess phenol up to 90 °C, whereas
organothorium complex 1-OAr rapidly forms (CGC)Th(OAr)2
at 25 °C. In situ generated precatalysts 1-OAr and 2-OAr
(24) (a) Golden, J. T.; Kazul’kin, D. N.; Scott, B. L.; Voskoboynikov, A. Z.;
Burns, C. J. Organometallics 2003, 22, 3971-3973. (b) Roussel, P.; Alcock,
N. W.; Boaretto, R.; Kingsley, A. J.; Munslow, I. J.; Sanders, C. J.; Scott,
P. Inorg. Chem. 1999, 38, 3651-3656. (c) Scott, P.; Hitchcock, P. B. Dalton
Trans. 1995, 603-609.
(25) (a) Brinkman, E. A.; Berger, S.; Brauman, J. I. J. Am. Chem. Soc. 1994,
116, 8304-8310. (b) Hopkinson, A. C.; Lien, M. H. J. Org. Chem. 1981,
46, 998-1003.
9
J. AM. CHEM. SOC. VOL. 129, NO. 19, 2007 6159

A R T I C L E S
Chart 2
Stubbert and Marks
exhibit near-identical catalytic properties vs isolated precatalysts,
and neither byproduct (CGC)Th(OAr)2 nor unreacted ArOH
significantly affects measured HA/cyclization Nt values, allow-
ing convenient precatalyst generation. In the solid state, 1-OAr
is monomeric and crystallizes in space group P21/c, displaying
a pseudotetrahedral coordination geometry (Figure 1d). The
near-linear 166.5(2)° Th-O-Cipso angle and Th-O distance
of 2.258(5) Å in 1-OAr are characteristic of the large -O-
2,6-tBu2C6H3 moiety (Chart 3).29 Cp′An(OAr)nR3-n com-
plexes display An-O-Cipso angles in the range 153.5-
(10)°-171.4(5)°, along with An-O distances ranging 2.14(1)-
flects the steric and electronic factors that promote unique
catalytic properties in (CGC)M3+/4+ complexes (Charts 3
and 4).3k,11,13,15,30
Related complexes 5-Cl and 6-Cl can be generated via
traditional salt metathesis or an alternative redistributive syn-
thesis (eq 3).17 The equilibrium lies g95% to the right for R )
CH3,9b,17 although the present bulkier R ) CH2SiMe3 substit-
uents undergo such conproportionations more sluggishly. The
2.189(6) Å (Th4+ 29a,b and 2.135(4)-2.29(1) Å (U4+).29c
)
Again, the coordinative unsaturation imparted by the CGC
ancillary ligation (Cp(centroid)-Th-N(tBu) ) 90.4°) re-
(26) For recent reviews on the chemistry of 4f and 5f elements, see: (a) Burns,
C. J.; Neu, M. P.; Boukhalfa, H.; Gutowski, K. E.; Bridges, N. J.; Rogers,
R. D. In ComprehensiVe Coordination Chemistry II; Abel, E. W., Stone,
F. G. A., Wilkinson, G., Eds.; Pergamon: New York, 1995; Vol. 4, pp
189-345. (b) Edelmann, F. T.; Freckmann, D. M. M.; Schumann, H. Chem.
ReV. 2002, 102, 1851-1896. (c) Molander, G. A.; Dowdy, E. D. Top.
Organomet. Chem. 1999, 2, 119-154. (d) Edelmann, F. T. Angew. Chem.,
Int. Ed. 1995, 34, 2466-88. (e) Edelmann, F. T. In ComprehensiVe
Organometallic Chemistry II; Abel, E. W.; Stone, F. G. A.; Wilkinson,
G., Eds.; Pergamon: New York, 1995; Vol. 4, pp 11-213. (f) Schaverien,
C. J. AdV. Organomet. Chem. 1994, 36, 283-362.
reverse disproportionation is therefore expected to be of minor
significance and is not detected by H NMR spectroscopy of
1
either 5-Cl or 6-Cl over several days at 25 °C or while heating
at 90 °C for >36 h. Moreover, addition of ca. 10-100 equiv of
Lewis basic amine substrate likely forms a species such as D
(eq 4; as in Cp′2Lns catalysts),1d,3a,v suggesting further steric
impediment to Cp′2An[N(H)R]Cl redistribution. Monomeric
imidoactinide complexes are typically stabilized by sterically
screening ancillary ligation, e.g., Cp′2An< as opposed to ansa
scaffolds Me2SiCp′′2An< and (CGC)An<, with more open
(27) Klooster, W. T.; Brammer, L.; Schaverien, C. J.; Budzelaar, P. M. H. J.
Am. Chem. Soc. 1999, 121, 1381-1382.
(28) For example, see: (a) Turner, L. E.; Thorn, M. G.; Fanwick, P. E.; Rothwell,
I. P. Organometallics 2004, 23, 1576-1593. (b) Rothwell, I. P. Chem.
Commun. 1997, 1331-1338. (c) Zambrano, C. H.; Profilet, R. D.; Hill, J.
E.; Fanwick, P. E.; Rothwell, I. P. Polyhedron 1993, 12, 689-708. (d)
Rothwell, I. P. Acc. Chem. Res. 1988, 21, 153-159. (e) Lateskey, S.;
Keddington, J.; McMullen, A. K.; Rothwell, I. P.; Huffman, J. C. Inorg.
Chem. 1985, 24, 995-1001 and references therein.
(29) (a) Clark, D. L.; Grumbine, S. K.; Scott, B. L.; Watkin, J. G. Organome-
tallics 1996, 15, 949-57. (b) Butcher, R. J.; Clark, D. L.; Grumbine, S.
K.; Scott, B. L.; Watkin, J. G. Organometallics 1996, 15, 1488-96. (c)
Berg, J. M.; Clark, D. L.; Huffman, J. C.; Morris, D. E.; Sattelberger, A.
P.; Streib, W. E.; Van der Sluys, W. G.; Watkin, J. G. J. Am. Chem. Soc.
1992, 114, 10811-21.
(30) For reviews of constrained geometry catalysts, see: (a) Gromada,
J.; Carpentier, J.-F.; Mortreux, A. Coord. Chem. ReV. 2004, 248,
397-410. (b) Okuda, J. Dalton Trans. 2003, 2367-2378. (c) Arndt, S.;
Okuda, J. Chem. ReV. 2002, 102, 1953-1976. (d) Britovsek, G. J. P.;
Gibson, V. C.; Wass, D. F. Angew. Chem., Int. Ed. 1999, 38, 428-
447.
9
6160 J. AM. CHEM. SOC. VOL. 129, NO. 19, 2007

Evidence for an M
−N
σ
-Bonded Insertive Pathway
A R T I C L E S
Chart 3
ence of excess protic amines (e.g., (tBu3Cp)2An< in eq 7).31a
Note that these synthetic routes appear generally inconsistent
with the present catalytic reaction rates (25 °C, C6D6) and
observed rate laws for aminoalkene and aminoalkyne HA/
cyclizations (vide infra).
Chart 4
Catalytic Intramolecular Hydroamination/Cyclization and
Mechanistic Considerations. In this section, the key features
of the two most plausible mechanistic scenarios, i.e.,
CdC/CtC insertion into an MsN(H)R linkage (Scheme 1) vs
formation of a reactive MdNR intermediate (Scheme 2),
followed by CdC/CtC cycloaddition, are considered, followed
by discussion of the data concerning intramolecular aminoalkyne
and aminoalkene HA/cyclization pathways for representative
primary and secondary amines mediated by (CGC)An< and
(CGC)Zr< complexes. Effects of the metal ionic radius as well
as σ and π ancillary ligation are discussed along with kinetic
parameters for CdC and CtC unsaturations. L2An< catalysts
are discussed first, followed by extension to (CGC)Zr<
catalysts. We begin with a summary of relevant mechanistic
observations.
structures leading to dimeric/oligomeric species.26,31 Imidoac-
tinide complexes are generally formed under forcing conditions
conducive to R-elimination (e.g., eq 5) or under milder condi-
tions employing reagents inducing oxidation to U6+, stabilizing
more open coordination environments (e.g., eq 6). Computa-
tional studies implicate 6d and 5f orbital involvement in
AndNR π-bonding with considerable positive charge at An (and
negative charge buildup at dNR).32 Moreover, L2AndNR
complexes revert to bis(amido)actinide complexes in the pres-
(31) For examples of L2AndNR complexes and their reactivity, see: (a) Zi,
G.; Blosch, L. L.; Jia, L.; Andersen, R. A. Organometallics 2005, 24, 4602-
4612. (b) Arney, D. S. J.; Burns, C. J. J. Am. Chem. Soc. 1995, 117, 9448-
60. (c) Brennan, J. G.; Andersen, R. A.; Zalkin, A. J. Am. Chem. Soc.
1988, 110, 4554-4558. (d) Morris, D. E.; DaRe, R. E.; Jantunen, K. C.;
Castro-Rodriguez, I.; Kiplinger, J. L. Organometallics 2004, 23, 5142-
5153. (e) Jantunen, K. C.; Burns, C. J.; Castro-Rodriguez, I.; Da Re, R.
E.; Golden, J. T.; Morris, D. E.; Scott, B. L.; Taw, F. L.; Kiplinger, J. L.
Organometallics 2004, 23, 4682-4692.
(32) (a) Bursten, B. E.; Strittmatter, R. J. Angew. Chem., Int. Ed. 1991, 30,
1069-1085. (b) Pepper, M.; Bursten, B. E. Chem. ReV. 1991, 91, 719-
741. (c) Burns, C. J.; Bursten, B. E. Comments Inorg. Chem. 1989, 9, 61-
93.
Summary of Mechanistically Relevant Results. Below is
a summary of the prominent features observed in HA/cyclization
kinetic and catalytic activity studies with L2M(NR2)X catalysts
1-6.
9
J. AM. CHEM. SOC. VOL. 129, NO. 19, 2007 6161

A R T I C L E S
Stubbert and Marks
reactions yields the rate law ν ∼ [L2Lns]1[base]-1 for large
[base]/[substrate], consistent with competitive inhibition of
CdC/CtC insertion.1d,3,4 From similar arguments, an analogous
pathway was proposed for L2Ln3+-mediated intermolecular HA
of alkenes, alkynes, and dienes, with the observed rate law ν ∼
[catalyst]1[alkyne]1[amine]0, consistent with turnover-limiting
CsC insertion into an LnsN bond, independent of amine
exchange.1d,3f Note that zero-order [amine] dependence is
expected for L2Lns catalysts incapable of forming charge-
neutral L2LndNR species and is consistent with immediate
catalyst activation/initiation of turnover by substrate and second-
ary amine reactivity. Also, the marked Nt dependence on ring
size, substrate tether (R-alkyl and gem-dialkyl substitutions;
Thorpe-Ingold effect),33 and CsC substituent electronic effects
(vs steric bulk) for alkene, alkyne, allene, and diene unsatura-
tions argue strongly against turnover-limiting heterocycle pro-
Table 5. Reported Mechanistic Characteristics of Various
Hydroamination Pathways
M
s
N(R
′
)R
MdNR
(Schemes 1,3)
(Scheme 2)
intramolecular HA
intermolecular HA
rate law
ν ∼ [M]1[N-H]0 a ν ∼ [M]1[N-H]-1[alkyne]1 b
induction period?
high [substrate]
low [substrate]
high [product]
∆H‡
no
yes
no effect
no effect
rate decreasec
∼10 kcal/mol
∼ -30 eu
yes
rate decrease
rate increase
∼no effectc
∼12 kcal/mold
∼ -45 eud
yes (M ) Zr)
no (M ) An)
no
∆S‡
C-C substitution
dependence?
2° amine substrates? yes
a For intramolecular hydroamination/cyclization. b The rate law ν ∼
[M]1[N-H]0[alkyne]0 is predicted for the scenario depicted in eq 8b.
Cp′2An<-catalyzed intermolecular HA: ν ∼ [M]1[N-H]-1[alkyne]0.
c Bulky products unable to induce competitive binding/inhibition. d Mea-
sured for Cp′2AnMe2-catalyzed intermolecular alkyne HA.
tonolysis after CsC insertion into MsN (i.e., kprotonolysis
>
kinsertion appears operative here).3a,x,5
The intermolecular HA pathway of Scheme 2 proceeds via
L2MdNR intermediate B that undergoes [2 + 2] cycloaddition
with disubstituted (reversible)8 or terminal (irreversible)9 alkynes.
This process typically displays a brief induction period and rate
law consistent with rapid pre-equilibrium loss of RNH2.
Cp2Zr<-catalyzed reactions require bulky amines able to
stabilize the Cp2ZrdNR intermediate, although excessive alkyne
steric bulk is unnecessary (eq 8a). Cp′2An<-mediated intermo-
lecular alkyne HA,9 complicated by concomitant alkyne oligo-
merization processes, behaves somewhat differently, exhibiting
the rate law ν ∼ [Cp′2An<]1[amine]-1[alkyne]0. In each case,
the nature of the amine substituents dictates rate and regiose-
lectivity. Note that, although Cp′2An< catalysts are active with
less bulky aliphatic amines, secondary amine HA apparently
does not proceed with either Cp2Zr< or Cp′2An< catalysts.
(i) Substituted (CGC)M(NR2)X-derived catalysts are fre-
quently more active than their traditional (CGC)MR2 counter-
parts (Tables 3-5).
(ii) Complete precatalyst activation by primary amine sub-
strates occurs within seconds at -78 °C in toluene-d8 solutions,
and bulkier secondary amine substrates are rapidly activated
under HA/cyclization catalysis conditions. Induction periods are
not observed with L2MR2 or L2M(R)X precatalysts (M ) Zr,
Th, U).
(iii) The observed rate law ν ∼ [L2M<]1[amine]0 is the same
for organo-4f-, (CGC)An<-,and (CGC)Zr<-catalyzed HA/
cyclizations (vide infra). Competitive binding/product inhibition
of catalytic turnover is sometimes observed at high product
concentrations (Figures 2c-d, 3c).
(iv) Ionic radius/metal accessibility trends for aminoalkyne
and aminoalkene HA/cyclization are conserved relative to
known L2Ln- and L2An<-catalyzed reactions (Tables 3-5).
(v) Both primary and secondary amine substrates are ef-
ficiently cyclized under mild reaction conditions (Tables 3-5).
Secondary aminoalkene HA/cyclization rates are not accelerated
in more polar solvent media.
Interestingly, however, cationic (Et2N)3U+BPh4 mediates the
-
catalytic addition of secondary Et2NH to alkynes.9a Although
inconsistent with synthetic L2AndNR chemistry for sterically
open ligands,26,31 an alternative scenario where an MdNR
species forms irreVersibly, followed by rapid CtC addition, is
conceivable (eq 8b).34 Key features and mechanistic implications
(33) (a) Jung, M. E.; Piizzi, G. Chem. ReV. 2005, 105, 1735-1766. (b) Sammes,
P. G.; Weller, D. J. Synthesis 1995, 1205-22.
(34) For the following pathway, where [A] ) [MdNR]:
(vi) Solution-phase magnetic moments of major (diamagnetic
or paramagnetic) catalyst species do not change upon precatalyst
activation or during/after catalytic runs.
(vii) Activation parameters measured for (CGC)M<-catalyzed
aminoalkyne and aminoalkene HA/cyclization are very similar
for both (CGC)MR2 and (CGC)M(NR2)X catalysts (M ) Th,
U, Zr). Moderate ∆H‡ and large negative ∆S‡ values are
characteristic of all L2Ln- and (CGC)An<-catalyzed HA/
cyclizations (vide infra; Table 6, Figures 2, 3).
Mechanistic Considerations. As noted above, the two most
plausible scenarios for intramolecular aminoalkene and ami-
noalkyne HA/cyclization are presented in Schemes 1 and 2
(Table 5). In the former, trivalent organolanthanides proceed
through highly polar, highly organized insertive four-center
transition states (Scheme 1, A). These reactions are characterized
by moderate ∆H‡ (ca. 12 kcal/mol) and large negative ∆S‡ (ca.
-30 eu) values, with their scope including primary and
secondary amine substrates.1d,3o,v Although [amine] and
[CsC] cannot be independently varied in intramolecular HA/
cyclization kinetic studies, addition of noncyclizable competing
Lewis bases (e.g., THF or n-propylamine) to intramolecular
9
6162 J. AM. CHEM. SOC. VOL. 129, NO. 19, 2007

Evidence for an M
−N
σ
-Bonded Insertive Pathway
A R T I C L E S
arises as to what effects are expected from the X ligand. Alkyl
hydrogenolysis and An-H olefin insertion processes have been
investigated for Cp′2An(R)X complexes as a function of R and
X (X ) OR′, Cl; eqs 9, 10).35 Here, electron-donating alkoxide
that would distinguish σ-bonded MsN(H)R vs π-bonded
MdNR L2M<-catalyzed HA pathways based on mechanistic
observations on L2Lns and Cp2Zr< and L2An< catalysts are
summarized in Table 5. Beyond observed rate laws, the most
strikingly different mechanistic characteristics concern the
presence of an induction period, during which catalyst generation
occurs (eq 8a), and an intrinsic inability to turn over secondary
amines (vide infra) via an MdNR pathway. This scenario also
exhibits a rate increase at low [amine] and rate decrease at high
[amine], owing to inhibition of MdNR formation during the
rapid pre-equilibrium (eq 8a). While an MsN(H)R pathway
mediates secondary NsH bond addition to CsC unsaturations,
competitive binding/product inhibition can sometimes lead to
moderate rate depression at high [product]. Note that although
inconsistent with observed reactivity trends and facile cyclization
of secondary amine substrates,11b the seemingly less likely case
of turnover-limiting heterocycle protonolysis following rapid
CsC insertion/extrusion (i.e., kinsertion > kprotonolysis) simplifies
the predicted rate law in eq 8a to ν ∼ [M]1[alkyne].1
coligands result in marked depression of reactivity, likely
reflecting -OR′ π-donation effects on An electrophilicity (cf.,
resonance forms F and G) as well as steric impediments. Parallel
Ligand and Metal Effects. Intramolecular aminoalkyne HA/
cyclization mediated by unsubstituted organoactinide complexes
1, 2, and 4-6 is broad in scope, with activity and selectivity
dependent on the An4+ ionic radius and ancillary ligation.11 For
less open Me2SiCp′′2An< and Cp′2An< complexes, primary
N-H bond addition to terminal and disubstituted aminoalkyne
substrates is generally more rapid for Th than for U complexes.
The rate disparity is greatest for hindered metallocene
Cp′2An< frameworks and least for more coordinatively unsatur-
ated Me2SiCp′′2An< frameworks. Similar rate dependences on
ancillary ligation are observed for Ln3+ catalysts, where smaller
Ln3+ ions and less accessible metal centers yield more active
catalysts. In contrast to organo-4f catalysts, trends for
(CGC)An< complexes 1 and 2 typify the enhanced aminoalkyne
catalytic activity imparted by CGC ancillary ligation,30 with far
greater catalytic efficiency for (CGC)An< vs less open L2An<
complexes. Here the smaller U4+ ion in 2 achieves the most
impressive Nt values, typically 10-100× greater than that for
organothorium complex 1, retaining the ionic radius dependence
observed with 4f catalysts and suggesting an intricate balance
between coordinative unsaturation, metal ionic radius, bond
covalency, and ligand/substrate electronic demands in organo-
actinide-mediated aminoalkyne HA/cyclization.11
trends are observed in both stoichiometric and catalytic Cp′2-
An(R)Cl complex reactivity, consistent with Cl-based π-dona-
tion effects.32 Computational and PES experiments also indicate
a strong dependence of non-Cp ligand σ-/π-donor properties
on the extent of bond covalency in actinocenes and argue that
interactions with actinide 6d orbitals dominate π-bonding,
consistent with observed effects on reactivity of electron-
withdrawing X substituents.32
While monoamido complexes 1-Cl, 2-Cl, 1-OAr, and 2-OAr
are effective precatalysts for aminoalkyne HA/cyclization,
reactivity trends for L2An(R)X complexes appear dependent on
a variety of factors, and direct comparisons of X effects are
complicated by the interplay between steric and electronic
factors.11b Given the impact of the An4+ ionic radius on
intramolecular HA/cyclization rates (Th4+ > U4+ for aminoalk-
enes vs U4+ > Th4+ for aminoalkynes) and greater metal center
access afforded by the open CGC ancillary ligand (vs Me2-
SiCp′′2An< and Cp′2An< catalysts),11b,30 the HA/cyclization
rate trends 1 > 1-Cl > 1-OAr and 2-Cl > 2 > 2-OAr observed
for primary aminoalkene conversion 11 f 12 (Table 3) are
similar to previously observed trends upon increasing metal
center accessibility. The pattern (CGC)An(NMe2)2 > (CGC)-
In the present study, (CGC)M(NR2)X-derived complexes (X
) Cl, aryloxide) were investigated because the corresponding
imido complexes (E) should not be readily accessible. It was
found that HA/cyclization rates are generally comparable to or
greater than those mediated by (CGC)M(NR2)2 precatalysts, and
within the context of a Schemes 1, 3 scenario, the question then
(35) (a) Lin, Z.; Marks, T. J. J. Am. Chem. Soc. 1990, 112, 5515-5525. (b)
Lin, Z.; Le Marechal, J.-F.; Sabat, M.; Marks, T. J. J. Am. Chem. Soc.
1987, 109, 4127-4129. (c) Lin, Z.; Marks, T. J. J. Am. Chem. Soc. 1987,
109, 7979-7985.
9
J. AM. CHEM. SOC. VOL. 129, NO. 19, 2007 6163

A R T I C L E S
Stubbert and Marks
Table 6. Experimental Activation Parameters for Intramolecular Aminoalkene and Aminoalkyne HA/Cyclization Catalyzed by Cp′2Ln-,
(CGC)An<, and (CGC)Zr< Complexes at g40 °C Temperature Range in C6D6
∆
H‡
∆
S‡
Ea
unsaturation
precatalyst
substrate
(kcal/mol)
(eu)
(kcal/mol)
ref
aminoalkene
Cp2′La[CH(SiMe3)2]
(CGC)Th(NMe2)2
(CGC)U(NMe2)OAr
(CGC)Th(NMe2)2
R ) R′ ) R′′ ) H, n ) 1
12.7(5)
12.6(5)
10(3)
-27(2)
-30(1)
-43(9)
-48(6)
13.4(5)
13.3(7)
11(3)
3v
11b
this work
this work
R ) Ph, R′ ) R′′ ) H, n ) 2
R ) Ph, R′ ) R′′ ) H, n ) 1 (11)
R ) Ph, R′ ) H, R′′ ) Me, n ) 1 (13)
2° aminoalkene
9(3)
10(3)
aminoalkyne
Cp2′Sm[CH(SiMe3)2]
(CGC)Th(NMe2)2
(CGC)U[N(SiMe3)2]Cl
(CGC)Zr(NMe2)Cl
R ) R′ ) R′′ ) H, n ) 1
11(8)
14(2)
16(3)
11(2)
-27(6)
-27(5)
-18(9)
-35(7)
3o
11b
this work
this work
R ) R′′ ) H, R′ ) Me, n ) 1 (9)
R ) R′′ ) H, R′ ) Me, n ) 1 (9)
R ) R′′ ) H, R′ ) SiMe3, n ) 1 (7)
15(2)
17(3)
12(2)
An(NMe2)Cl > (CGC)An(NMe2)OAr observed for 13 f 14
HA/cyclization (Table 4) is consistent with diminished impor-
tance of the An4+ ionic radius with secondary amino-
alkene substrates and reflects the substantial steric crowding
afforded by the 2,6-di-tert-butylphenoxide ligand for an already
congested CdC insertion into an MsN(R′)R bond (cf., R3 *
H in C, Scheme 3). Note that although CGC-imposed geo-
metric constraints are uniform, the presence of a relatively small,
relatively nonlabile chloride ligand as opposed to an encum-
bered, substrate-derived amido moiety should reduce HA
transition state steric congestion. For aminoalkyne HA/cycliza-
tion, the general trend 1-Cl > 1 > 1-OAr is observed for An
) Th, while trends for An ) U (i.e., 2 > 2-Cl > 2-OAr, R )
SiMe3, 7 f 8; 2 > 2-OAr > 2-Cl, R ) Me, 9 f 10) vary with
alkyne substitution (Table 2), providing additional evidence for
increased importance of transition state electronic demands in
aminoalkyne HA/cyclization.1d,3,4,11b This is also seen with
secondary aminoalkyne cyclization 15 f 16, where the less
hindered chloride ligand effects less rapid Nt with (CGC)M-
(NR2)Cl for M ) Zr, Th, U, though (CGC)An< complexes
retaining their reactivity advantage11,30 over Cp′2An< catalysts
(Table 4). Interestingly, with the exception of 15 f 16,
monoamido zirconium precatalyst 3-Cl is a more efficient
precatalyst than 3 in mediating the aminoalkene and ami-
noalkyne transformations investigated here, suggesting that
decreased steric hindrance outweighs electronic demands for
Zr-mediated intramolecular HA/cyclization.
precatalysts, where reversible ring dissociation is less likely.17,36
GC/MS and 1H NMR analyses of reaction mixtures during and
immediately following 7 f 8 cyclization give no sign of HCp′
or single-ring Cp′An< species, arguing that ring protonolysis
is unlikely (eq 12). Interestingly, a 100× decrease in activity
is observed in these complexes vs Cp′2An< for conversion 7
f 8 (Table 2), perhaps reflecting the pronounced deactivation
by the chloride ligand electronic characteristics as discussed
above for An-R hydrogenolysis/An-H olefin insertion pro-
cesses (eq 9, 10).35 Decreased electrophilicity could reduce
alkyne insertion rates, depressing Nt vs Cp′2An<, Me2SiCp′′2-
An<, and (CGC)An< catalysts.37 Alternatively, the agency of
Cp′2AndNR species in the sterically protected Cp′2 environment
could explain diminished reactivity vs more open ancillary
ligation favoring MsN(H)R intermediates, especially in light
of the reported difficulty of cycloadding CdC bonds to
MdNR bonds (M ) Ti, Zr).1,10 However, that Cp′2An<
complexes mediate intramolecular aminoalkyne HA/cyclization
of primary and secondary amines with zero-order dependence
on [amine] and without protonolytic HCp′ release argues for a
σ-bonded MsN insertive pathway, even in sterically congested
environments.
Metallocenes 4/4-Cl (Me2SiCp′′2U<), 5/5-Cl (Cp′2Th<), and
6/6-Cl (Cp′2U<) were also investigated as precatalysts in
aminoalkyne 7 f 8 HA/cyclization. The catalytic activity of
ansa-metallocenes 4 and 4-Cl is largely unaffected by chloride
incorporation. However, potential Cp′′ ring detachment (eq 11),
A ligand dissociation/reattachment process analogous to eqs
11 and 12 is in principle possible with CGC ancillary ligation
(eq 13). Although not spectroscopically observed, the chelating
(tBu)N-An4+ moiety in (CGC)An< complexes could be
displaced in the presence of a large excess of substrate
(36) (a) Arduini, A. L.; Edelstein, M.; Jamerson, J. D.; Reynolds, J. G.; Schimd,
K.; Takats, J. Inorg. Chem. 1981, 20, 2470-2474. (b) Fagan, P. J.;
Manriquez, J. M.; Vollmer, S. H.; Day, C. S.; Day, V. W.; Marks, T. J. J.
Am. Chem. Soc. 1981, 103, 2206-2220.
(37) (a) Lanza, G.; Fragala, I. L.; Marks, T. J. Organometallics 2002, 21, 5594-
5612. (b) Lanza, G.; Fragala, I. L.; Marks, T. J. Organometallics 2001,
20, 4006-4017. (c) Lanza, G.; Fragala, I. L.; Marks, T. J. J. Am. Chem.
Soc. 2000, 122, 12764-12777.
previously observed for mixed-ring organolanthanide catalysts,3r,s
prompted a more thorough investigation of the Cp′2AnR2
9
6164 J. AM. CHEM. SOC. VOL. 129, NO. 19, 2007

Evidence for an M
−N
σ
-Bonded Insertive Pathway
A R T I C L E S
molecules, enabling transient AndNR formation (eq 13a, R′ )
H) and, potentially, CdC/CtC [2 + 2] cycloaddition. However,
the catalytic activity of any L2M< complex with secondary
amine substrates (eq 13b, R′ * H) with observed rate law ν ∼
[M]1[amine]0 provides compelling evidence for an insertive Ms
N(R′)R pathway (Scheme 3), and the comparable competence
of substituted and unsubstituted 1-2 in mediating such trans-
formations argues that an L2AndNR imidoactinide intermediate
(B) is not catalytically important here. Passage through an
heterocycle yield and regioselectivity in radical-mediated ami-
noalkene cyclizations.39b,c
(CGC)Zr<-Mediated Hydroamination. Initial intramolecu-
lar aminoalkyne HA/cyclization reports have proposed the
involvement of in situ generated CpMdNR(Cl) species (M )
Ti, Zr) at high catalyst loadings (g20 mol %), starting from
i
CpM(CH3)2Cl or CpMCl3 with 40 mol % Pr2NEt in THF.7f,g
More recently, well-defined group 4 amidate, metallocene, and
chelating diamide complexes have been applied to primary
aminoalkyne (K; M ) Ti, Zr; R ) H, Me)7b and aminoalkene
(L; 120-150 °C) HA/cyclizations, invoking similar MdNR
pathways.6d Sterically open homoleptic Ti(NMe2)4 also mediates
L2MdNR reactive intermediate requires an unprecedented high-
energy species similar to H or I in lieu of the more reasonable
J. Saltlike structure H would presumably be generated via
R-hydrogen abstraction8,9,38 and involves hypervalent N bonded
directly to M4+, whereas zwitterionic I (via electron pair transfer
from N to the AnsN bond) places a formal negative charge on
An4+ or Zr4+ (no change in diamagnetism or µeff is observed
during primary or secondary amine HA/cyclization). Moreover,
intramolecular primary aminoalkene HA/cyclization.6e Although
it is again reasonable to expect electron-withdrawing chloride
ligands to reduce catalytic activity,35 substituted 3-Cl is typically
the more efficient (CGC)Zr< precatalyst found in this study.
For the Me3Si-substituted aminoalkyne conversion 7 f 8, this
difference is quite pronounced (Table 2), and for transformations
9 f 10 and 11 f 12 (Tables 3, 4), the distinction is again
significant, displaying a roughly 2- to 3-fold enhancement vs
complex 3. The activities of 3-Cl and 3 in mediating 11 f 12
at 100 °C are roughly 4× and 2× greater, respectively, than
electron-rich precatalyst L6d (Ti(NMe2)4 is ca. 2× less active
than L).6e Secondary amine 13 f 14 and 15 f 16 HA/
cyclizations mediated by (CGC)Zr< are considerably more
sluggish than those with (CGC)An< catalysts, reflecting metal
accessibility effects on Nt.1,3,11b The added steric hindrance in
secondary vs primary aminoalkenes 13 (Table 4) and 11 (Table
3), where cyclization rates are comparable, is offset by the
enhanced transition state orientation (Thorpe-Ingold effect)33
of substrate chain gem-diphenyl vs gem-dimethyl groups.
Furthermore, in light of the similar catalytic behavior of
(CGC)An< and (CGC)Zr< catalysts, the Nt trends (3-Cl > 3
for 11 f 12 vs 3 > 3-Cl for 15 f 16) presumably reflect the
importance of transition-state steric demands, where the small,
rigid chloride ligand provides a less hindered site for CdC/
CtC insertion, perhaps outweighing electronic deactivation (cf.,
Scheme 1, A and Scheme 3, C). In addition, while cationic
group 3 catalysts mediate intramolecular primary aminoalkene
species H or I should be stabilized in more polar media, contrary
to the observed Nt decrease for 2 (rapid catalyst decomposition
occurs with 1). Also note that the high yields and regioselectivity
in the present aminoalkene and aminoalkyne HA/cyclizations
are inconsistent with radical (chain) processes (eqs 14, 15).39
The required but energetically unfavorable An4+ f An3+
electron transfer/reduction process (particularly for An ) Th),26
rate dependence on the metal ionic radius, zero-order depen-
dence on [substrate],20 and pronounced effects of ancillary
ligation on Nt and diastereoselectivity all render radical pathways
that are unlikely, particularly in light of reported trends in
(38) An analogous mechanism is invoked in imidotitanium synthesis: Hazari,
N.; Mountford, P. Acc. Chem. Res. 2005, 38, 839-849.
(39) (a) Walton, J. C.; Studer, A. Acc. Chem. Res. 2005, 38, 794-802. (b)
Kemper, J.; Studer, A. Angew. Chem., Int. Ed. 2005, 44, 4914-4917. (c)
Newcomb, M.; Burchill, M. T.; Deeb, T. M. J. Am. Chem. Soc. 1988, 110,
6528-6535.
-
HA/cyclization,4a,h and Cp2ZrMe+MeB(C6F5)3 effects more
9
J. AM. CHEM. SOC. VOL. 129, NO. 19, 2007 6165

A R T I C L E S
Stubbert and Marks
thermodynamically favorable1 primary aminoallene HA/
an analogous kH/kD ) 4.2 is reported at 40 °C for chiral
binaptholate Ln complexes.4b The marked HA/cyclization rate
dependence on ring size and alkyl chain substitution in addition
to other arguments1d suggest that the significant N-H/N-D KIE
does not result from turnover-limiting protonolysis of completely
cyclized aminoalkene but rather that protonolysis may be
concurrent with cyclization. In the present study, the observed
kH/kD ) 3.3(5) and 2.6(4) for 2 and 2-Cl, respectively, are in
excellent agreement with Ln-mediated aminoalkene HA/cy-
clization results (eq 16), further supporting an MsN σ-bonded
mechanistic pathway (Scheme 1). To our knowledge, similar
-
cyclization,7b cationic L2M(R)+XB(C6F5)3 (M ) Ti4+, Zr4+
;
R ) Me, Ch2Ph; X ) C6F5, R) catalysts are only active for
secondary amine intramolecular HA/cyclizations.10 Interestingly,
the poisoning of these cationic catalysts by primary amine
substrates has been rationalized as deactivation via unreactiVe
neutral imido complex formation.8-10,38 Taken together, these
observations, in conjunction with the present results, argue that
it is not necessary to invoke MdNR intermediates in intramo-
lecular HA/cyclization reactions mediated by organozirconium
catalysts and that a σ-bonded MsN mechanistic pathway is
accessible and perhaps faVored.
Activation Parameter Parallels. Activation parameters
determined for intramolecular HA/cyclization mediated by
monoamido (CGC)M(NR2)X catalysts (M ) An, Zr) are
comparable to those for similar processes mediated by L2AnR2
and L2LnR catalysts (Table 6). The moderate ∆H‡ and large
negative ∆S‡ values are consistent with highly ordered CdC/
CtC insertive transition states having considerable bond-
forming accompanying bond-breaking.40 The change in ∆S‡ to
more negative values with 11 f 12 conversion mediated by
2-OAr (∆S‡ ) -43(9) eu) is consistent with the transition state
ordering necessary to accommodate the steric hindrance of the
large aryloxide ligand (M; cf., C, Scheme 3). A similar change
in ∆S‡ for HA/cyclization 13 f 14 mediated by 1 (∆S‡ ) -48-
(6) eu) is also not surprising given the nonbonding repulsions
engendered by the N-methyl group of 13 and substrate organiza-
tion required prior to CdC insertion (N; cf., C, Scheme 3). To
our knowledge, activation parameters have not been reported
for group 4 mediated HA/cyclizations,1,6,7 although intermo-
lecular terminal alkyne + aliphatic amine HA mediated by
KIE studies have not been reported in group 4 catalysts, where
aminoalkene HA is typically sluggish, limiting direct compari-
sons with organolanthanide catalysts. However, in the unimo-
lecular R-elimination process shown in eq 17, where an
MdNR species is generated with bulky R ) Si(tBu)3 groups, a
significantly larger KIE is observed with kH/kD ) 5.9(6) and
7.3(4) for M ) Ti, Zr, respectively.42 This stark contrast in
Cp′2AnMe2 also displays comparable parameters, ∆H‡
)
11.7(3) kcal/mol and ∆S‡ ) -44.5(8) eu.41 That the present
NsH/NsD KIEs suggests that unimolecular MdNR formation
is not significant in the turnover-limiting step of (CGC)An<-
mediated intramolecular HA/cyclization.
Mechanistic Summary. It is useful to briefly summarize the
observations supporting the basic HA/cyclization pathway of
Scheme 3. The present (CGC)M< catalysts could reasonably
mediate intramolecular HA/cyclization via either of two plau-
sible mechanistic scenarios: (1) a highly polar, highly organized
four-centered, insertive transition state involving catalytically
active (CGC)M< species possessing two MsN(H)R σ-bonds
(“Ln-like”; Scheme 1) or (2) a [2 + 2] cycloaddition probably
following a rapid pre-equilibrium (step (i), Scheme 2) that
generates L2MdNR reactive intermediate B. Note that stable
monomeric L2AndNR complexes invoked in scenario (2) are
challenging synthetic targets (vide supra), particularly with
unencumbered ancillary ligation,31 and that imidoactinide
complexes typically revert to bis(amido)actinides in the presence
of excess amine (cf., eq 7b).31a
activation parameters parallel those for L2Ln- and L2An<-
catalyzed HA/cyclizations1d,3,11 suggests that the mechanism and
turnover-limiting steps in each process are very similar if not
identical. Zero-order substrate kinetic dependence, characteristic
of intramolecular HA (Table 5),1 indicates that a rapid pre-
equilibrium involving RNH2 extrusion is not significant, while
the ready cyclization of secondary amine substrates argues
against the involvement of conventional MdNR species pro-
duced via R-H elimination.
Kinetic Isotope Effects. In a similar organolanthanide
aminoalkene HA/cyclization, substantial deuterium KIEs are
observed in the range kH/kD ) 2.7(4)-5.2(8), varying with
substrate structure and temperature from 25 to 60 °C,3v while
The data here support mechanistic scenario (1) (Scheme 3),
with perhaps the strongest evidence opposing scenario (2) (eq
8; Scheme 2) being the ability of (CGC)An(NMe2)2, (CGC)-
(40) (a) Illuminati, G.; Mandolini, L. Acc. Chem. Res. 1981, 14, 95-102. (b)
Mandolini, L. J. Am. Chem. Soc. 1978, 100, 550-554.
(41) The experimentally determined ∆S‡ ) -44.5(8) eu for intermolecular HA
is representative of a bimolecular CtC insertion process, as opposed to
the unimolecular insertion proposed for intramolecular HA/cyclization (∆S‡
ca. -30 eu). See ref 1d for details.
(42) (a) Cummins, C. C.; Schaller, C. P.; Van Duyne, G. D.; Wolczanski, P.
T.; Chan, A. W. E.; Hoffman, R. J. Am. Chem. Soc. 1991, 113, 2985-
2994. (b) Cummins, C. C.; Baxter, S. M.; Wolczanski, P. T. J. Am. Chem.
Soc. 1988, 110, 8731-8733.
9
6166 J. AM. CHEM. SOC. VOL. 129, NO. 19, 2007

Evidence for an M
−N
σ
-Bonded Insertive Pathway
A R T I C L E S
ZrMe2, and (CGC)M(NR2)X precatalysts 1-6 to effectively
mediate secondary N-alkyl aminoalkene and aminoalkyne HA/
cyclizations. The relative depression in Nt for secondary vs
primary substrates is consistent with trends previously observed
for L2Ln- catalysts, where diminished turnover frequencies can
be attributed to unfavorable steric interactions.1d,3,4 In the present
study, secondary amine HA/cyclizations proceed without devia-
tion from the observed primary amine rate law, ν ∼
[L2M<]1[amine]0, and with similar activation energetics, arguing
that a mechanistic scenario similar to Scheme 3 is again
operative. While a pathway proceeding through an active
L2MdNR species (B) is conceivable in unsubstituted L2MR2
complexes with primary amine substrates, the mild reaction
conditions, absence of required steric bulk in amine substrates,
facile cyclization of 2° amine substrates, and lack of an induction
period prior to catalytic turnover argue against scenario (2)/
Scheme 2. Moreover, the [amine]-1 kinetics seen in [2 + 2]
cycloaddition pathways8 differs from the present results, where
high [product] sometimes depresses Nt owing to competitive
binding/inhibition (Table 5).1d,3v,11 Devoid of unlikely intermedi-
ates H or I and without detectable ancillary ligand detachment
or rearrangement (eqs 2, 3, 11-13), there are no obvious
pathways from L2M(NR2)X complexes 1-6 to the MdNR
species required in scenario (2), making this pathway unlikely
for either primary or secondary amine substrates.
evidence for a mechanistic pathway proceeding via CdC/
CtC insertion at an MsN(H)R σ-bond (Schemes 1, 3),
particularly with sterically open CGC ancillary ligation in the
presence of excess amine substrate. The ability of
(CGC)MR2 and (CGC)M(NR2)X complexes to effectively
promote HA/cyclization of both primary and secondary ami-
noalkyne and aminoalkene substrates with comparable rates and
activation parameters argues that MdNR intermediates are
unlikely and that a pathway involving insertion at an MsN
σ-bonded intermediate is kinetically viable. Moreover, activities
of selectively substituted (CGC)M(NR2)X complexes generally
exceed those of (CGC)MR2 precatalysts, further supporting
passage through a transition state similar to A or C with a strong
dependence on nonbonded interactions and CdC/CtC insertion
into an MsN(H)R σ-bonded intermediate (Scheme 3).
Acknowledgment. The National Science Foundation (CHE-
0415407) is gratefully acknowledged for funding this research.
We also thank Ms. C. L. Stern for assistance with X-ray
diffraction data collection as well as Mr. M. R. Salata and Dr.
A. K. Dash for helpful discussions.
Supporting Information Available: Full experimental details,
including precatalyst syntheses, methods for kinetic studies, and
X-ray diffraction analyses with Crystallographic Information
Files and data tables for 1-Cl, 2-Cl, 3-Cl, and 1-OAr. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Conclusions
Catalytic intramolecular HA/cyclization reactions mediated
by selectively substituted 5f and d0 complexes provide strong
JA0675898
9
J. AM. CHEM. SOC. VOL. 129, NO. 19, 2007 6167