Organolanthanide-catalyzed intramolecular hydroamination/cyclization of aminoalkynes

Article abstract of DOI:10.1021/ja9612413

This contribution reports the efficient and regiospecific Cp'₂LnCH(SiMe₃)₂ (Ln = La, Nd, Sm, Lu; Cp' = η⁵-Me₅C₅)- and Me₂SiCp''₂LnCH(SiMe₃)₂ (Ln = Nd, Sm; Cp'' = η⁵-Me₄C₅)-catalyzed hydroamination/cyclization of aliphatic and aromatic aminoalkynes of the formula RC≡C(CH₂)(n)NH₂ to yield the corresponding cyclic imines RCH₂C=N(CH₂)(n-1)CH₂, where R, n, N(t) h^-1 (°C) = Ph, 3, 77 (21°C); Ph, 3, 2830 (60°C); Me, 3, 96 (21°C); CH₂=CMeCH₂, 3, 20 (21°C); H, 3, 580 (21°C); Ph, 4, 4 (21°C); Ph, 4, 328 (60°C); Ph, 5, 0.11 (60°C); and SiMe₃, 3, >7600 (21°C), and of aliphatic secondary amino-alkynes of the formula RC≡C(CH₂)₃NHR₁ to generate the corresponding cyclic enamines RCH=CNR₁(CH₂)₂CH₂ where R, R₁, N(t) h^-1 (°C) = SiMe₃, CH₂=CHCH₂, 56 (21°C); H, CH₂=CHCH₂, 27 (21°C); SiMe₃, CH₂=CH(CH₂)₃, 129 (21°C); and H, CH₂=CH(CH₂)₃, 47 (21°C). Kinetic and mechanistic evidence is presented arguing that the turnover-limiting step is an intramolecular alkyne insertion into the Ln-N bond followed by rapid protonolysis of the resulting Ln-C bond. The use of larger metal ionic radius Cp'₂LnCH(SiMe₃)₂ and more open Me₂SiCp''₂LnCH(SiMe₃)₂ complexes as the precatalysts results in a decrease in the rate of hydroamination/cyclization, arguing that the steric demands in the -C≡C- insertive transition state are relaxed compared to those of the analogous aminoolefin hydroamination/cyclization.

Full text of DOI:10.1021/ja9612413

J. Am. Chem. Soc. 1996, 118, 9295-9306
9295
Organolanthanide-Catalyzed Intramolecular Hydroamination/
Cyclization of Aminoalkynes
Yanwu Li and Tobin J. Marks*
Contribution from the Department of Chemistry, Northwestern UniVersity, 2145 Sheridan Road,
EVanston, Illinois 60208-3113
ReceiVed April 15, 1996X
Abstract: This contribution reports the efficient and regiospecific Cp′2LnCH(SiMe3)2 (Ln ) La, Nd, Sm, Lu; Cp′ )
η5-Me5C5)- and Me2SiCp′′2LnCH(SiMe3)2 (Ln ) Nd, Sm; Cp′′ ) η5-Me4C5)-catalyzed hydroamination/cyclization
of aliphatic and aromatic aminoalkynes of the formula RCtC(CH2)nNH2 to yield the corresponding cyclic imines
RCH2CdN(CH2)n-1CH2, where R, n, Nt h-1 (°C) ) Ph, 3, 77 (21 °C); Ph, 3, 2830 (60 °C); Me, 3, 96 (21 °C);
CH2dCMeCH2, 3, 20 (21 °C); H, 3, 580 (21 °C); Ph, 4, 4 (21 °C); Ph, 4, 328 (60 °C); Ph, 5, 0.11 (60 °C); and
SiMe3, 3, >7600 (21 °C), and of aliphatic secondary amino-alkynes of the formula RCtC(CH2)3NHR1 to generate
the corresponding cyclic enamines RCHdCNR1(CH2)2CH2 where R, R1, Nt h-1 (°C) ) SiMe3, CH2dCHCH2, 56
(21 °C); H, CH2dCHCH2, 27 (21 °C); SiMe3, CH2dCH(CH2)3, 129 (21 °C); and H, CH2dCH(CH2)3, 47 (21 °C).
Kinetic and mechanistic evidence is presented arguing that the turnover-limiting step is an intramolecular alkyne
insertion into the Ln-N bond followed by rapid protonolysis of the resulting Ln-C bond. The use of larger metal
ionic radius Cp′2LnCH(SiMe3)2 and more open Me2SiCp′′2LnCH(SiMe3)2 complexes as the precatalysts results in a
decrease in the rate of hydroamination/cyclization, arguing that the steric demands in the sCtCs insertive transition
state are relaxed compared to those of the analogous aminoolefin hydroamination/cyclization.
Introduction
selectivities,1b,d,3 or in transition metal-mediated systems with
generally short catalyst lifetimes, low turnover frequencies, and/
or limited reaction scope (via metal activation of either the amine
or the carbon-carbon multiple bond).4,5 In comparison to
typical middle and late transition metal complexes, organolan-
thanides exhibit distinctive reactivity characteristics for unsatur-
ated organic substrate activation and heteroatom transforma-
tions.6 These derive mainly from the high electrophilicity of
f-element centers, mechanistic pathways different from con-
ventional oxidative addition/reductive elimination sequences,
relatively large ionic radii, nondissociable ancillary ligation, and
high kinetic lability. The facile catalysis of aminoolefin
hydroamination/cyclization by organolanthanides7 demonstrates
that the insertion of olefinic functionalities into Ln-N bonds
in bis(cyclopentadienyl)lanthanide environments can be coupled
Carbon-nitrogen bond-forming processes are of fundamental
importance in organic chemistry, and olefin or alkyne hy-
droamination by catalytic N-H bond addition to unsaturated
carbon-carbon multiple bonds represents both a challenging
and highly desirable transformation.1,2 In many cases, such
reactions only proceed with alkali metals in liquid ammonia at
high temperatures and pressures, affording modest yields and
X Abstract published in AdVance ACS Abstracts, September 1, 1996.
(1) For general references, see: (a) March, J. AdVanced Organic
Chemistry, 4th ed.; J. Wiley & Sons: New York, 1992; pp 768-770, and
references therein. (b) Brunet, J.-J.; Neibecker, D.; Niedercorn, F. J. Mol.
Catal. 1989, 49, 235-259. (c) Collman, J. P.; Hegedus, L. S.; Norton, J.
R.; Finke, R. G. Principles and Applications of Organotransition Metal
Chemistry; University Science Books: Mill Valley, CA, 1987; Chapters
7.4, 17.1. (d) Trost, B. M.; Verhoeven, T. R. In ComprehensiVe Organo-
metallic Chemistry; Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds.;
Pergamon Press: Oxford, U.K., 1982; Vol. 8, pp 892-895, and references
therein. (e) Gibson, M. S. In The Chemistry of the Amino Group; Patai,
S., Ed.; Interscience: New York, 1968; pp 61-65.
(2) For leading reviews of amine additions to olefins and alkynes, see:
(a) Hegedus, L. S. Angew. Chem., Int. Ed. Engl. 1988, 27, 1113-1126. (b)
Gasc, M. B.; Latties, A.; Perie, J. J. Tetrahedron 1983, 39, 703-731. (c)
Ba¨ckvall, J.-E. Acc. Chem. Res. 1983, 16, 335-342 (d) Ja¨ger, V.; Viehe,
H. G. Houben-Weyl, Methoden der Organischen Chemie; Thieme Verlag:
Stuttgart, Germany, 1977; Vol. 5/2a, pp 713-724. (e) Suminov, S. I.; Kost,
A. N. Russ. Chem. ReV. 1969, 38, 884-899. (f) Chekulaeva, I. A.;
Kondrat’eva, L. V. Russ. Chem. ReV. 1965, 34, 669-680.
(5) For hydroamination of alkenes and alkynes mediated by middle and
late transition metals, see: (a) Brunet, J.-J.; Neibecker, D.; Philippot, K.
Tetrahedron Lett. 1993, 34, 3877-3880. (b) Tamaru, Y.; Hojo, M.;
Higashimura, H.; Yoshida, Z.-I. J. Am. Chem. Soc. 1988, 110, 3994-4002,
and references therein. These authors summarize the strengths and
weaknesses of platinum metal-catalyzed transformations. (c) Casalnuovo,
A. L.; Calabrese, J. C.; Milstein, D. J. Am. Chem. Soc. 1988, 110, 6738-
6744. (d) Fukuda, Y.; Utimoto, K.; Nozaki, H. Heterocycles 1987, 25,
297-300. (e) Hegedus, L. S.; Mckearin, J. M. J. Am. Chem. Soc. 1982,
104, 2444-2451. (f) Pugin, B.; Venanzi, L. M. J. Organomet. Chem. 1981,
214, 125-133, and references therein. (g) Barluenga, J.; Azar, F.; Liz, R.;
Rodes, R. J. Chem. Soc., Perkin Trans. 1980, 2732-2737. (h) Coulson,
D. R. Tetrahedron Lett. 1971, 429-430. Coulson, D. R. U.S. Pat. 3,758,
586, 1973. (i) Reference 1c,d.
(6) For general organolanthanide reviews, see: (a) Schumann, H.; Meese-
Marktscheffel, J. A.; Esser, L. Chem. ReV. 1995, 95, 865-986, and
references therein. (b) Schaverien, C. J. AdV. Organomet. Chem. 1994,
36, 283-362, and references therein. (c) Evans, W. J. AdV. Organomet.
Chem. 1985, 24, 131-177, and references therein. (d) Schumann, H. In
Fundamental and Technological Aspects of Organo-f-Element Chemistry;
Marks, T. J., Fragala, I., Eds.; D. Reidel: Dordrecht, Holland, 1985; Chapter
1. (e) Kagan, H. B.; Namy, J. L. In Handbook on the Physics and Chemistry
of Rare Earths; Gschneider, K. A., Eyring, L., Eds.; Elvesier: Amsterdam,
1984; Chapter 50. (f) Forsberg, J. H.; Hoeller, T. In Gmelin Handbook of
Inorganic Chemistry; Moeller, T., Kmerke, Y., Schleitzer-Rust, E., Eds.;
Springer: Berlin, 1983; pp 137-303. (g) Marks, T. J., Ernst, R. D. In
ComprehensiVe Organometallic Chemistry; Wilkinson, G., Stone, F. G. A.,
Abel, E. W., Eds.; Pergamon Press: Oxford, U.K., 1982; Chapter 21.
(3) For hydroamination of olefins using alkali metals at high temperatures
and pressures, see: (a) Pez, G. P.; Galle, J. E. Pure Appl. Chem. 1985, 57,
1917-1926. (b) Howk, B. W.; Little, E. L.; Scott, S. L.; Whitman, G. M.
J. Am. Chem. Soc. 1954, 76, 1899-1902.
(4) For hydroamination mediated by early transition metals, see: (a)
McGrane, P. L.; Livinghouse, T. J. Am. Chem. Soc. 1993, 115, 11485-
11489. (b) Baranger, A. M.; Walsh, P. J.; Bergman, R. G. J. Am. Chem.
Soc. 1993, 115, 2753-2763. (c) Walsh, P. J.; Hollander, F. J.; Bergman,
R. G. Organometallics 1993, 12, 3705-3723. (d) McGRane, P. L.;
Livinghouse, T. J. Org. Chem. 1992, 57, 1323-1324. (e) McGrane, P. L.;
Jensen, M.; Livinghouse, T. J. Am. Chem. Soc. 1992, 114, 5459-5460. (f)
Walsh, P. J.; Baranger, A. M.; Bergman, R. G. J. Am. Chem. Soc. 1992,
114, 1708-1719. This article begins with a review of conventional
hydroamination processes for unsaturated carbon-carbon bonds. (g) Walsh,
P. J.; Hollander, F. J.; Bergman, R. G. J. Am. Chem. Soc. 1988, 110, 8729-
8730.
S0002-7863(96)01241-3 CCC: $12.00 © 1996 American Chemical Society

9296 J. Am. Chem. Soc., Vol. 118, No. 39, 1996
Li and Marks
Scheme 1. Proposed Mechanism for
Organolanthanide-Catalyzed Aminoolefin
Hydroamination/Cyclization
Scheme 2. Simplified Catalytic Cycle for the
Hydroamination/Cyclization of Aminoalkynes
amine protonolysis of the resulting Ln-C bond (step 2) is
estimated to be ∼10-20 kcal/mol less exothermic (approxi-
mately thermoneutral). If the insertion of alkyne functionalities
into Ln-N bonds were indeed efficient and analogous to those
transformations established for aminoolefins,7c-g,14 such ami-
noalkyne-based catalytic processes would offer a route to a
diverse variety of heterocycles and natural product skeletons
(e.g., indolizidines, quinolizidines) as well as a complement to
recently reported organo group 4-centered stoichiometric4a,d,e
and catalytic4 alkyne hydroamination processes which proceed
via an entirely different (noninsertive) mechanistic pathway.4f
In this contribution, we present a full discussion of our studies
of efficient, regiospecific aminoalkyne hydroamination/cycliza-
tion processes within lanthanide coordination spheres, including
studies of reaction scope, substrate substituent, metal, and
ancillary ligand effects, as well as of kinetics and mechanism.15
with rapid Ln-C protonolysis to effect efficient and regiospe-
cific catalytic N-C bond-forming processes (Scheme 1, Cp′ )
η5-Me5C5; Ln ) lanthanide).
Literature precedent8 for alkyne insertion into lanthanide
metal-alkyl σ bonds and thermodynamic considerations10-13
pose an interesting situation for aminoalkynes (Scheme 2).
Alkyne insertion into Ln-N bonds (step 1) is estimated to be
∼35 kcal/mol more exothermic than for olefins,10-13 while
(7) Alkene insertions involving Ln-heteroatom bonds: (a) Li, Y.; Marks,
T. J. J. Am. Chem. Soc. 1996, 118, 707-708. (b) Li, Y.; Marks, T. J.
Abstracts of Papers, 34th National Organic Symposium; ACS Division of
Organic Chemistry, Williamsburg, VA, June 1995; American Chemical
Society: Washington, DC, 1995; Abstr. 44. (c) Giardello, M. A.; Conticello,
V. P.; Brard, L.; Gagne, M. R.; Marks, T. J. J. Am. Chem. Soc. 1994, 116,
10241-10254. (d) Gagne´, M. R.; Stern, C. L.; Marks, T. J. J. Am. Chem.
Soc. 1992, 114, 275-294. (e) Giardello, M. A.; King, W. A.; Nolan, S.
P.; Porchia, M.; Sishta, C.; Marks, T. J. In Energetics of Organometallic
Species; Martinho Simoes, J. A., Ed.; Kluwer: Dordrecht, Holland, 1992;
pp 35-54. (f) Gagne´, M. R.; Brard, L.; Conticello, V. P.; Giardello, M.
A.; Stern, C. L.; Marks, T. J. Organometallics 1992, 11, 2003-2005. (g)
Gagne´, M. R.; Nolan, S. P.; Marks, T. J. Organometallics 1990, 9, 1716-
1718.
(8) Alkyne insertions involving Ln-alkyl or An-alkyl bonds: (a) Straub,
T.; Haskel, A.; Eisen, M. S. J. Am. Chem. Soc. 1995, 117, 6364-6365. (b)
Heeres, H. J.; Nijhoff, J.; Teuben, J. H. Organometallics 1993, 12, 2609-
2617. (c) Evans, W. J.; Keyer, R. A.; Ziller, J. W. Organometallics 1992,
12, 2618-2633. (d) Heeres, H. J.; Teuben, J. H. Organometallics 1991,
10, 1980-1986, and references therein. (e) Heeres, H. J.; Heeres, A.;
Teuben, J. H. Organometallics 1990, 9, 1508-1510. (f) Heeres, H. J.;
Meetsma, A.; Teuben, J. H.; Rogers, R. D. Organometallics 1989, 8, 2637-
2646. (g) Den Haan, K. H.; Wielstra, Y.; Teuben, J. H. Organometallics
1987, 6, 2053-2060. (h) Reference 7a.
(9) An organoactinide-catalyzed intermolecular alkyne hydroamination
process has recently been shown to occur via an actinide imido complex
(Cp′2AndNR): Haskel, A. H.; Straub, T.; Eisen, M. S., private communica-
tion.
(10) Requisite experimental thermochemical data are not available to
compare the thermodynamics of amine addition to olefins with that to
alkynes. However, ∆H for NH3 addition to ethylene can be estimated from
thermochemical data13 to be -13 kcal/mol. Calculations at the AM-1 level
place NH3 addition to acetylene (to yield CH3CHdNH) as ∼17 kcal/mol
more exothermic than to ethylene. Furthermore, the addition of CH4 to
acetylene is estimated from thermochemical data13 to be ∼14 kcal/mol more
exothermic and ∼14 kcal/mol more exergonic than that to ethylene.
(11) Metal-ligand bond enthalpies from: (a) Nolan, S. P.; Stern, D.;
Hedden, D.; Marks, T. J. ACS Symp. Ser. 1990, No. 428, 159-174. (b)
Nolan, S. P.; Stern, D.; Marks, T. J. J. Am. Chem. Soc. 1989, 111, 7844-
7853. (c) Schock, L. E.; Marks, T. J. J. Am. Chem. Soc. 1988, 110, 7701-
7715. (d) Bruno, J. W.; Marks, T. J.; Morss, L. R. J. Am. Chem. Soc.
1983, 105, 6824-6832. (e) Reference 7e.
(12) Organic fragment bond enthalpies from: (a) Griller, D.; Kanabus-
Kaminska, J. M.; Maccoll, A. J. Mol. Struct. 1988, 163, 125-131. (b)
McMillan, D. F.; Golden, D. M. Annu. ReV. Phys. Chem. 1982, 33, 493-
532, and references therein. (c) Benson, S. W. Thermochemical Kinetics,
2nd ed.; John Wiley and Sons: New York, 1976; Appendix tables A.10,
A.11, A.22. (d) Benson, S. W. J. Chem. Educ. 1965, 42, 502-518.
(13) Pedley, J. B.; Naylor, R. D.; Kirby, S. P. Thermochemical Data of
Organic Compounds, 2nd ed.; Chapman and Hall: London, 1986; Appendix
tables 1, 3.
(14) Alkene insertions involving Ln-alkyl bonds: (a) Molander, G. A.;
Nichols, P. J. J. Am. Chem. Soc. 1995, 117, 4415-4416. (b) Casey, C. P.;
Hallenbeck, S. L.; Pollok, D. W.; Landis, C. R. J. Am. Chem. Soc. 1995,
117, 9770-9771. (c) Fu, P.-F.; Brard, L.; Li, Y.; Marks, T. J. J. Am. Chem.
Soc. 1995, 117, 7157-7168. (d) Fu, P.-F.; Marks, T. J. J. Am. Chem. Soc.
1995, 117, 10747-10748. (e) Yang, X.; Seyam, A. M.; Fu, P.-F.; Marks,
T. J. Macromolecules 1994, 27, 4625-4626. (f) Molander, G. A.; Hoberg,
J. O. J. Am. Chem. Soc. 1992, 114, 3123-3124. (g) den Haan, K. H.; de
Boer, J. L.; Teuben, J. H.; Spek, A. L.; Kajic-Prodic, B.; Hays, G. R.; Huis,
R. Organometallic 1986, 5, 1726-1733. (h) Watson, P. L.; Parshall, G.
W. Acc. Chem. Res. 1985, 18, 51-55. (i) Jeske, G.; Lauke, H.; Mauermann,
H.; Swepston, P. N.; Schumann, H.; Marks, T. J. J. Am. Chem. Soc. 1985,
107, 8091-8103. (j) Li, Y.; Marks, T. J., manuscript in preparation. (k)
Reference 7a.

Hydroamination/Cyclization of Amino Alkynes
J. Am. Chem. Soc., Vol. 118, No. 39, 1996 9297
of distilled H2O, and the layers were separated. The aqueous phase
was extracted with 3 × 25 mL of diethyl ether. The combined ether
extracts and organic phase were washed with 100 mL of brine, dried
over MgSO4, and filtered, and the ether and THF removed from the
filtrate by rotary evaporation. Distillation (96-100 °C (0.05 mmHg))
of the residue gave 47.0 g (88% yield) of colorless ClCH2CH2-
CH2CtCPh: 1H NMR (300 MHz, CDCl3) δ 7.45 (m, 2H, Ph), 7.32
(m, 3H, Ph), 3.74 (t, J ) 6.38 Hz, 2H, CH2Cl), 2.63 (t, J ) 6.81 Hz,
2H, CH2CtC), 2.08 (m, 2H, CH2).
(b) N-(5-Phenyl-4-pentynyl)phthalimide (1b). Compound 1a and
54.0 g (0.29 mol) of potassium phthalimide were heated at 100 °C
overnight in 350 mL of DMF. After cooling, the solution was poured
into a mixture of CHCl3 (500 mL) and H2O (500 mL). The aqueous
phase was separated and extracted with 3 × 40 mL of CHCl3. The
combined CHCl3 solutions and the organic phase were washed with
300 mL of 0.2 N KOH (to remove unreacted phthalimide) and 300
mL of H2O, respectively. After drying over MgSO4 and filtration, the
CHCl3 and DMF were removed in vacuum, and the crystalline residue
was triturated with 2 × 80 mL of diethyl ether. After collection by
filtration, the solid residue was dried at reduced pressure to give 55.0
g (69% yield) of colorless crystalline C8H4O2N CH2CH2CH2CtCPh:
1H NMR (400 MHz, CDCl3) δ 7.85 (m, 2H, Ph), 7.69 (m, 2H, Ph),
7.32 (m, 2H, Ph), 7.25 (m, 3H, Ph), 3.90 (t, J ) 7.00 Hz, 2H, CH2N),
2.54 (t, J ) 7.00 Hz, 2H, CH2Ct), 2.06 (m, 2H, CH2).
(c) 5-Phenyl-4-pentyn-1-amine (1). Compound 1b and 20.0 g (0.40
mol) of hydrazine monohydrate in 450 mL of CH3OH were refluxed
for 1 h. The reaction mixture was then cooled to 0 °C and filtered.
The colorless solids were washed with 3 × 10 mL of CH3OH, and the
organic phase was concentrated to an oily residue by rotary evaporation.
Distillation (88-89 °C (0.05 mmHg)) afforded 7.0 g (22% yield) of
H2NCH2CH2CH2CtCPh as a colorless oil. The NMR data agree with
literature data:4e 1H NMR (300 MHz, CDCl3) δ 7.35 (m, 2H, Ph), 7.24
(m, 3H, Ph) 2.84 (t, J ) 6.87 Hz, 2H, CH2N), 2.45 (t, J ) 6.89 Hz,
2H, CH2CtC), 1.71 (m, 2H, CH2), 1.22 (br s, 2H, NH2); 13C NMR
(75 MHz, 1H-decoupled, CDCl3) δ 131.5 (CH), 128.2 (CH), 127.6 (CH),
123.8 (C of Ph), 89.5 (CtC) 80.9 (CtC), 41.3 (CH2N), 32.4 (CH2),
16.8 (CH2).
Experimental Section
Materials and Methods. All manipulations of air-sensitive materi-
als were carried out with rigorous exclusion of oxygen and moisture
in flame-dried Schlenk-type glassware on a dual-manifold Schlenk line,
interfaced to a high-vacuum (10-6 Torr) line, or in a nitrogen-filled
Vacuum Atmospheres glovebox with a high-capacity recirculator (1-2
ppm of O2). Argon (Matheson, prepurified) was purified by passage
through a MnO oxygen-removal column16 and a Davision 4A molecular
sieve column. Before use, all solvents were distilled under dry nitrogen
over appropriate drying agents (sodium benzophenone ketyl, metal
hydrides of Na/K alloy except for chlorinated solvents). Deuterium
oxide and chloroform-d were purchased from Cambridge Isotope
Laboratories. Benzene-d6 and toluene-d8 (Cambridge Isotope Labo-
ratories; all 99+ atom % D) used for NMR reactions and kinetic
measurements were stored in vacuo over Na/K alloy in resealable bulbs
and vacuum-transferred immediately prior to use. All organic starting
materials were purchased from Aldrich Chemical Co., Farchan Labo-
ratories Inc., or Lancaster Synthesis Inc. and, when appropriate, were
distilled prior to use. The substrates 5-phenyl-4-pentyn-1-amine (1),4e
4-hexyn-1-amine (3),17a and 6-phenyl-5-hexyn-1-amine (11)4e were
synthesized according to literature procedures. The substrates 4-octyn-
7-methyl-7-en-1-amine (5), 4-pentyn-1-amine (7), 5-(trimethylsilyl)-
4-pentyn-1-amine (9), 7-phenyl-6-heptyn-1-amine (13), N-allyl-5-
(trimethylsilyl)-4-pentyn-1-amine (15), N-allyl-4-pentyn-1-amine (17),
N-4-penten-5′-(trimethylsilyl)-4′-pentyn-1-amine (19), and N-4-penten-
4′-pentyn-1-amine (21) were synthesized via modifications of literature
methods as described below. Substrates 1, 3, 5, 9, 11, 13, 15, and 19
were dried by stirring over BaO, and substrates 7, 17, and 21 by stirring
over CaH2 overnight. Substrates were then repeatedly dried by vacuum
transfer onto and from freshly activated Davison 4A molecular sieves
and were degassed by freeze-pump-thaw methods. They were then
stored in vacuum-tight storage flasks. The organolanthanide precata-
lysts Cp′2LnCH(SiMe3)2 (Ln ) La, Nd, Sm, Lu; Cp′ ) η5-Me5C5)14j
and Me2SiCp′′2LnCH(SiMe3)2 (Ln ) Nd, Sm; Cp′′ ) η5-Me4C5)18a were
prepared by published procedures.
Physical and Analytical Measurements. NMR spectra were
1
recorded on either a Varian Gemini VXR 300 (FT, 300 MHz, H; 75
Synthesis of 4-Hexyn-1-amine (3). A solution of 75.0 g (0.73 mol)
of 5-chloro-1-pentyne in 500 mL of THF at -78 °C was treated while
stirring with n-BuLi (0.73 mol) for 1 h, and then CH3I (0.73 mol) was
added dropwise. The reaction mixture was then stirred while warming
to room temperature. After 1 h reflux, the solution was poured into
250 mL of distilled H2O, followed by separation. The aqueous phase
was extracted twice with diethyl ether (2 × 100 mL). The combined
organic phase and ether extracts were then washed with a saturated
NaCl solution (100 mL), dried over MgSO4, and filtered. Removal of
the solvents from the filtrate by rotary evaporation gave 6-chloro-2-
hexyne (3a). The reaction of 3a with sodium phthalimide (0.23 mol)
in 300 mL of DMF at 60 °C overnight afforded N-4-hexynylphthal-
imide. This compound was used directly for the next step without
further purification. N-4-Hexynylphthalamide and hydrazine mono-
hydrate (0.18 mol) in 500 mL of EtOH were heated with stirring at 60
°C overnight. After the mixture was cooled to room temperature,
followed by addition of 70 mL of concentrated HCl, the solution was
heated at 60 °C for an additional 4 h. The mixture was then cooled
and filtered, and the colorless precipitate washed with 2 × 100 mL of
EtOH. Removal of solvent from the filtrate at reduced pressure gave
a white precipitate. The white solid was then treated with a mixture
of KOH (2 N, 150 mL) and diethyl ether (300 mL). After separation,
the organic phase was extracted with 3 × 200 mL of diethyl ether.
The ether phase was then washed with a saturated NaCl solution and
dried over MgSO4. After filtration and removal of solvent from the
filtrate by rotary evaporation, distillation (68-69 °C (23 mmHg))
afforded 5.0 g (34% yield) of H2NCH2CH2CH2CtCCH3 (3c) as a
colorless oil. The NMR spectra agree with published data:17a 1H NMR
(300 MHz, CDCl3) δ 2.80 (t, J ) 6.87 Hz, 2H, CH2N), 2.20 (m, 2H,
CH2CtC), 1.78 (t, J ) 2.51 Hz, 3H, CH3), 1.63 (m, 2H, CH2), 1.63
(br s, NH2); 13C NMR (75 MHz, 1H-decoupled, CDCl3) δ 78.5
(CtCMe), 75.9 (tCCH3), 41.2 (CH2N), 32.5 (CH2CH2N), 16.1
MHz, 13C) or XL-400 (FT, 400 MHz, H; 100 MHz, 13C) instrument.
1
1
Chemical shifts (δ) for H and 13C are referenced to internal solvent
resonances and reported relative to SiMe4. NMR experiments on air-
sensitive samples were conducted in Teflon valve-sealed tubes (J.
Young). Analytical gas chromatography was performed on a Varian
Model 3700 gas chromatograph with FID detectors and a Hewlett-
Packard 3390A digital recorder/integrator using a 0.125 in. i.d. column
with 3.8% (w/w) SE-30 liquid phase on Chromosorb W support. GC/
MS studies were conducted on a VG 70-250 SE instrument with 70
eV electron impact ionization. IR spectra were recorded using a Nicolet
520 FT-IR spectrometer with MCT detector. Melting points and boiling
points are uncorrected.
Synthesis of 5-Phenyl-4-pentyn-1-amine (1). (a) 5-Chloro-1-
phenyl-1-pentyne (1a). A solution of 47.0 g (0.30 mol) of 3-bromo-
1-chloropropane in 200 mL of THF was treated dropwise with 300
mL (0.30 mol) of lithium phenylacetylide while stirring at 0 °C for 2
h. The reaction mixture was then warmed to room temperature and
refluxed for 3 h. The reaction solution was next poured into 120 mL
(15) Alkyne insertions involving Ln-heteroatom bonds: (a) Li, Y.; Fu,
P.-F.; Marks, T. J. Organometallics 1994, 13, 439-440. (b) Li, Y.; Marks,
T. J. Organometallics, in press. (c) Reference 7a,b.
(16) (a) He, M.-Y.; Xiong, G.; Toscano, P. J.; Burwell, R. L., Jr.; Marks,
T. J. J. Am. Chem. Soc. 1985, 107, 641-652. (b) Moeseler, R.; Horvath,
B.; Lindenau, D.; Horvath, E. G.; Krauss, H. L. Z. Naturforsch. 1976, 31B,
892-893. (c) McIlwrick, C. R.; Phillips, C. S. G. J. Phys., E 1973, 6,
1208-1210.
(17) (a) Tietze, L. F.; Bratz, M.; Pretor, M. Chem. Ber. 1989, 122, 1955-
1961. (b) Negishi, E.; Boardman, L. D.; Sawada, H.; Bagheri, V.; Stoll,
A. T.; Tour, J. M.; Rand, C. L. J. Am. Chem. Soc. 1988, 110, 5383-5396.
(c) Fujikura, S.; Inoue, M.; Utimoto, K.; Nozaki, H. Tetrahedron Lett. 1984,
25, 1999-2002. (d) Flahaut, J.; Miginiac, P. HelV. Chim. Acta 1978, 61,
2275-2285.
(18) (a) Jeske, G.; Schock, L. E.; Mauermann, H.; Swepston, P. N.;
Schumann, H.; Marks, T. J. J. Am. Chem. Soc. 1985, 107, 8103-8110. (b)
Jeske, G.; Lauke, H.; Mauermann, H.; Schumann, H.; Marks, T. J. J. Am.
Chem. Soc. 1985, 107, 8111-8118. (c) Reference 14j.
1
(CH2CtC), 4.13 (Me); 13C NMR (100 MHz, H-coupled, CDCl3) δ
78.5 (s, CtCMe), 75.9 (s, tCCH3), 41.9 (t, JCH ) 135 Hz, CH2N),
33.2 (t, JCH ) 128 Hz, CH2CH2N), 16.8 (t, JCH ) 131 Hz, CH2CtC),

9298 J. Am. Chem. Soc., Vol. 118, No. 39, 1996
Li and Marks
4.1 (q, JCH ) 132 Hz, CH3); IR (CHCl3) 2050, 1588 cm-1; MS (rel
abundance) M+ (10), M+ - 1 (55), 82.1 (100), 80.1 (43), 79.1 (30),
77.0 (17), 65.0 (100), 56.0 (15), 53.0 (25), 51.0 (14), 44.0 (11), 43.0
(34); high-resolution mass spectrum, calcd for C6H11N (M+) 97.0891,
found 97.0895.
mass spectrum calcd for C5H8N (M+ - 1) 82.0657, found 82.0628.
Anal. Calcd for C5H9N: C, 72.24; H, 10.91; N, 16.84. Found: C,
72.16; H, 11.33; N, 16.88.
Synthesis of 5-(Trimethylsilyl)-4-pentyn-1-amine (9). (a) 5-Bromo-
1-(trimethylsilyl)-1-pentyne (9a). A procedure similar to that for 1a
utilizing the lithium (trimethylsilyl)acetylide obtained from the reaction
of n-butyllithium (0.25 mol) with (trimethylsilyl)acetylene (25.0 g, 0.25
mol) and 1,3-dibromopropane (50.0 g, 0.25 mol) instead of 3-bromo-
1-chloropropane gave 36.0 g (65% yield) of BrCH2CH2CH2CtCSiMe3.
1H NMR (300 MHz, CDCl3) data agree with literature data:17c-e δ 3.52
(t, J ) 6.48 Hz, 2H, CH2Br), 2.42 (t, J ) 6.66 Hz, 2H, CH2CtC),
2.05 (m, 2H, CH2), 0.16 (s, 9H, SiMe3).
Compound 3 was dissolved in dry diethyl ether; hydrogen chloride
gas was then bubbled into the solution to form a white precipitate.
After filtration, the solid was washed with dry diethyl ether and
recrystallized from a mixture of EtOH and ethyl acetate to give
HCl‚H2NCH2CH2CH2CtCCH3: 1H NMR (300 MHz, D2O) δ 2.88 (t,
J ) 8.34 Hz, 2H, CH2N), 2.06 (m, 2H, CH2CtC), 1.61 (m, 2H, CH2),
5
1.54 (t, J ) 2.55 Hz, 3H, CH3).
(b) N-[5-(Trimethylsilyl)-4-pentynyl]phthalimide (9b). The pro-
cedure was the same as for 1b except that the solid product was
recrystallized from 100 mL of distilled H2O and washed with 2 × 20
mL of H2O. The product, C8H4O2NCH2CH2CH2CtCSiMe3, was
isolated in 53% yield (24.5 g), mp 77.5-78.5 °C: 1H NMR (300 MHz,
CDCl3) δ 7.85 (m, 2H, Ph), 7.74 (m, 2H, Ph), 3.78 (t, J ) 6.93 Hz,
2H, CH2N), 2.32 (t, J ) 7.14, 2H, CH2CtC), 1.94 (m, 2H, CH2), 0.09
(s, 9H, SiMe3).
Synthesis of 4-Octyn-7-methyl-7-en-1-amine (5). A solution of
18.0 g (0.175 mol) of ClCH2CH2CH2CtCH in 150 mL of pentane
was treated with 0.175 mol of n-BuLi at 0 °C over a period of 1 h.
The reaction mixture was stirred for 10 h at room temperature and
then refluxed for an additional 2 h. Next, the reaction mixture was
cooled to 0 °C, and 25.0 g (0.275 mol) of ClCH2C(Me)dCH2 in 150
mL of THF was syringed into the solution over a period of 10 min.
The mixture was then stirred at 0 °C for 10 h, warmed to room
temperature, stirred for 2 h, and then refluxed for 8 h. The mixture
was cooled to room temperature, and 300 mL of water was added to
the solution. After separation of organic and aqueous phases, the
aqueous phase was extracted with 3 × 100 mL of diethyl ether. The
combined organic phase and ether extracts were washed with 150 mL
of saturated NaCl solution and then dried over MgSO4 overnight.
Removal of the solvent by rotary evaporation followed by trap-to-trap
distillation gave 11.2 g (41% yield) of colorless CH2dC(Me)-
CH2CtCCH2CH2CH2Cl.
The reaction of 11.2 g (0.072 mol) of CH2dC(Me)CH2CtCCH2-
CH2CH2Cl with 20.0 g (0.11 mol) of sodium phthalimide in 300 mL
of DMF at 60 °C overnight afforded N-4-octynyl-7-methyl-7-ene-
phthalimide. This compound was used directly for the next step without
further purification. N-4-Octynyl-7-methyl-7-enephthalimide and hy-
drazine monohydrate (0.202 mol) in 250 mL of EtOH were heated
with stirring at 60 °C for 4 days. After the mixture was cooled to
room temperature, the colorless precipitate was then filtered off.
Removal of solvent from the filtrate by rotary evaporation gave a
colorless crude product. Distillation (80-83 °C (8 mmHg)) of the
residue afforded 2.43 g (total, 10% yield) of H2NCH2CH2CH2CtCCH2C-
(Me)dCH2 as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 4.96 (s,
1H, CHd), 4.79 (s, 1H, CHd), 2.84 (s, 2H, dCCH2Ct), 2.78 (t, J )
6.74 Hz, 2H, NCH2), 2.24 (m, 2H, CH2Ct), 1.75 (s, 3H, Me), 1.62
(m, 2H, CH2), 0.47 (br, 2H, NH2); 13C (75 MHz, CDCl3) δ 141.2, 111.2,
81.9, 77.5, 41.2, 32.5, 27.5, 22.1, 16.2; MS (rel abundance) M+ (85),
M+ + 1 (34), 122.1 (74), 120.1 (30), 109.1 (97), 105.1 (85), 91.1 (94),
82.0 (88), 77.0 (81), 65.0 (35), 51.0 (40), 41.0 (351), 39.0 (100); high-
resolution mass spectrum, calcd for C9H15N (M+) 137.1204, found
137.1201.
(c) 5-(Trimethylsilyl)-4-pentyn-1-amine (9). A procedure similar
to that for 1 was used except that the reaction mixture was refluxed
for 24 h, yielding 5.1 g (38% yield) of 9: 1H NMR (300 MHz, CDCl3)
δ 2.79 (t, J ) 6.87 Hz, 2H, CH2N), 2.28 (t, J ) 7.00 Hz, 2H, CH2CtC),
1.85 (br s, NH2) 1.64 (m, 2H, CH2), 0.12 (s, 9H, SiMe3); 13C NMR
1
(75 MHz, H-decoupled, CDCl3) δ 106.8 (CtC), 84.97 (CtC), 41.2
(CH2N), 32.1 (CH2, 17.4 (CH2), 0.2 (SiMe3); 13C NMR (75 MHz, 1H-
coupled, CDCl3) δ 106.5 (s, CtC), 85.1 (s, CtC), 41.0 (t, JCH ) 134
Hz, CH2N), 31.7 (t, JCH ) 128 Hz, CH2), 17.4 (t, JCH ) 131 Hz, CH2),
0.2 (q, JCH ) 119 Hz, SiMe3); IR (CHCl3) 2171, 1589 cm-1. MS (rel
abundance) M+ (7), M+ - 1 (5), M+ + 1 (2), 140.1 (30), 138.1 (37),
123.1 (38), 109.0 (20), 98.0 (13), 82.1 (100), 73.0 (73), 67.0 (10), 59.0
(20), 43.0 (49), 35.0 (9); high-resolution mass spectrum, calcd for C8H17-
NSi(M+) 155.1130, found 155.1135.
Synthesis of 6-Phenyl-5-hexyn-1-amine (11). (a) 6-Chloro-1-
phenyl-1-hexyne (11a). 11a was synthesized in a manner analogous
to that for 1a using 38.0 g (0.30 mol) of 1,4-dichlorobutane in place of
3-bromo-1-chloropropane. Distillation at 94-95 °C (0.2 mmHg) gave
19.5 g (34% yield) of Cl(CH2)4CtCPh as a colorless oil. The 1H NMR
(300 MHz, CDCl3) spectra agree with the published data:4a δ 7.35 (m,
2H, Ph), 7.24 (m, 3H, Ph), 3.57 (t, J ) 6.59 Hz, CH2Cl), 2.43 (t, J )
6.86 Hz, 2H, CH2Ct), 1.93 (m, 2H, CH2CH2Cl), 1.73 (m, 2H, CH2).
(b) N-(6-Phenyl-5-hexynyl)phthalimide (11b). 11b was prepared
in a fashion analogous to 1b using 11a. After washing with diethyl
ether and drying in vacuum, 21.0 g (69% yield) of C8H4O2NCH2CH2-
CH2CH2CtCPh was obtained as a colorless solid: 1H NMR (300 MHz,
CDCl3) δ 7.86 (m, 2H, Ph), 7.71 (m, 2H, Ph), 7.39 (m, 2H, Ph), 7.27
(m, 3H, Ph), 3.76 (t, J ) 7.00 Hz, CH2N), 2.48 (t, J ) 7.00 Hz,
CH2CtC), 1.88 (m, 2H, CH2CH2N), 1.66 (m, 2H, CH2).
(c) 6-Phenylhex-5-yn-1-amine (11). 11 was synthesized in a
manner analogous to 1 using 11b and H2NNH2‚H2O. Distillation (88-
89 °C (∼0.05 mmHg)) afforded 2.1 g (18% yield) of H2NCH2CH2-
CH2CH2CtCPh as a colorless oil. The NMR data agree with published
data:4e 1H NMR (300 MHz, CDCl3) δ 7.40 (m, 2H, Ph), 7.27 (m, 3H,
Ph), 2.75 (t, J ) 6.80 Hz, 2H, CH2N), 2.44 (t, J ) 6.56 Hz, 2H,
CH2CtC), 1.64 (m, 4H, 2CH2), 1.23 (br, 2H, NH2); 13C NMR (75
MHz, H-decoupled, CDCl3) δ 131.5 (CH), 128.2 (CH), 127.5 (CH),
123.9 (C of Ph), 90.0 (CtC), 80.8 (CtC), 41.8 (CH2N), 33.1 (CH2),
26.1 (CH2), 19.3 (CH2).
Synthesis of 7-Phenylhept-6-yn-1-amine (13). (a) 7-Bromo-1-
phenyl-1-heptyne (13a). A procedure similar to those described above
was used to prepare 13a using 84.0 g (0.36 mol) of 1,5-dibromopentane
in place of 3-bromo-1-chloropropane. Distillation (164-167 °C (0.05
mmHg)) afforded 49.0 g (52% yield) of Br(CH2)5CtCPh: 1H NMR
(400 MHz, CDCl3) δ 7.36 (m, 2H, Ph), 7.24 (m, 3H, Ph), 3.41 (t, J )
7.00 Hz, 2H, CH2Br), 2.40 (t, J ) 6.20 Hz, 2H, CH2CtC), 1.89 (m,
2H, CH2CH2Br), 1.60 (m, 4H, 2CH2).
(b) N-(7-Phenyl-6-heptynyl)phthalimide (13b). 13b was synthe-
sized in a manner analogous to that for 1b. Recrystallization from
diethyl ether gave 46.0 g (74% yield) of C8H4O2NCH2CH2CH2CH2-
CH2CtCPh as a colorless solid: 1H NMR (400 MHz, CDCl3) δ 7.82
(m, 2H, Ph), 7.69 (m, 2H, Ph), 7.34 (m, 2H, Ph), 7.24 (m, 3H, Ph),
Synthesis of 4-Pentyn-1-amine (7). A suspension of 49.0 g (0.487
mol) of 5-chloro-1-pentyne, 109.0 g (0.582 mol) of sodium phthalimide,
and 300 mg of NaI in 300 mL of DMF was heated at 100 °C overnight
to afford N-4-pentynylphthalimide. This compound was used directly
for the next step without further purification. N-4-Pentynylphthalimide
and hydrazine monohydrate (1.00 mol) in 800 mL of MeOH were
heated with stirring at 60 °C overnight. After the mixture was cooled
to room temperature, followed by addition of 70 mL of concentrated
HCl, the solution was heated at 60 °C for an additional 4 h. The mixture
was then cooled and filtered, and the white precipitate washed with 2
× 100 mL of EtOH. Removal of solvent from the combined filtrates
at reduced pressure gave a white precipitate. The colorless solid was
then treated with a mixture of KOH (2 N, 350 mL) and diethyl ether
(300 mL). After separation, the organic phase was extracted with 3 ×
200 mL of diethyl ether. The ether phase was then washed with brine
(100 mL) and dried over Na2SO4. After filtration and removal of
solvent from the filtrate by rotary evaporation, distillation (124-125
°C) afforded 12.5 g (32% yield) of H2NCH2CH2CH2CtCH as a
colorless oil: 1H NMR (300 MHz, C6D6) δ 2.44 (t, J ) 6.75 Hz, 2H,
CH2N), 1.98 (m, 2H, CH2CtC), 1.79 (m, 1H, HCt), 1.31 (m, 2H,
CH2), 0.38 (br s, NH2); 13C NMR (75 MHz, C6D6) δ 84.3, 68.8, 41.1,
32.6, 15.9; MS (rel abundance) M+ (92), M+ - 1 (1), M+ + 1 (32),
65.1 (16), 55.1 (52), 51.0 (22), 43.0 (100), 39.0 (52); high-resolution
1

Hydroamination/Cyclization of Amino Alkynes
J. Am. Chem. Soc., Vol. 118, No. 39, 1996 9299
3.71 (t, J ) 7.20 Hz, 2H, CH2N), 2.41 (t, J ) 6.81 Hz, CH2CtC),
1.71 (m, 2H, CH2CH2N), 1.65 (m, 2H, CH2CH2CtC), 1.51 (m, 2H,
CH2).
extracted with 3 × 100 mL of diethyl ether. The combined ethereal
extracts and the organic phase were washed with 70 mL of brine, dried
over MgSO4, and concentrated by rotary evaporation. Distillation (99-
101 °C (34 mmHg)) gave 4.9 g (55% yield) of HCtCCH2CH2CH2-
NHCH2CHdCH2 as a colorless oil: 1H NMR (300 MHz, CDCl3) δ
5.87 (m, 1H, CHd), 5.13 (m, 2H, CH2d), 3.23 (d, J ) 4.50 Hz, 2H,
NCH2CHd), 2.70 (t, J ) 7.05 Hz, 2H, NCH2), 2.25 (m, 2H, CH2Cd),
1.93 (t, J ) 2.70 Hz, 1H, HCt), 1.70 (m, 2H, CH2), 1.57 (br, 1H,
NH); 13C (75 MHz, CDCl3) δ 136.7, 116.0, 84.0, 68.6, 52.3, 48.1, 28.6,
16.3; MS (rel abundance) M+ (16), M+ - 1 (43), M+ - 2 (10), 108.1
(11), 96.1 (25), 80.1 (13), 70.1 (100), 65.1 (6), 54.1 (13), 41.1 (94);
high-resolution mass spectrum, calcd for C8H12N (M+ - 1) 122.0970,
found 122.0970.
Preparation of N-4-Pentenyl-5′-(trimethylsilyl)-4′-pentyn-1-amine
(19). The title compound was synthesized in a manner analogous to
that for N-allyl-5-(trimethylsilyl)-4-pentyn-1-amine (15) using 4.0 g
(0.023 mol) of 1-chloro-5-(trimethylsilyl)-4-pentyne and 17.7 g (0.208
mol) of 4-penten-1-amine to afford 3.1 g (61% yield) of Me3-
SiCtCCH2CH2CH2NHCH2CH2CH2CHdCH2 (bp 70-73 °C (0.10
mmHg)) as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 5.79 (m,
1H, CHd), 4.95 (m, 2H, CH2d), 2.68 (t, J ) 7.05 Hz, 2H, NCH2),
2.59 (t, J ) 7.35 Hz, 2H, NCH2), 2.26 (t, J ) 7.05 Hz, 2H, tCsCH2),
2.06 (m, 2H, CH2CHd), 1.67 (m, 2H, CH2CH2N), 1.58 (m, 2H,
NCH2CH2CH2CHd), 1.20 (br, 1H, NH), 0.11 (s, 9H, SiMe3); 13C NMR
(75 MHz, CDCl3) δ 138.5, 114.6, 106.9, 84.8, 49.3, 48.8, 31.5, 29.3,
28.7, 17.8, 0.10; MS (rel abundance) M+ - 1 (1), 208.1 (8), 194.0 (1),
180.0 (2), 168.0 (27), 155.0 (18), 140.0 (19), 123.0 (5), 98.0 (35), 73.0
(100), 59.0 (15), 44.0 (43); high-resolution mass spectrum, calcd for
C13H24NSi (M+ - 1) 222.1678, found 222.1683.
Preparation of N-4-Pentenyl-4′-pentyn-1-amine (21). The title
compound was synthesized in a manner analogous to that for N-allyl-
4-pentyn-1-amine (17) using 0.86 g (4.9 mmol) of 1-chloro-5-
(trimethylsilyl)-4-pentyne and 3.8 g (44.6 mmol) of 4-penten-1-amine
to afford 0.40 g (54% yield) of HCtCCH2CH2CH2NHCH2CH2CH2-
CHdCH2 (bp 132-133 °C (31 mmHg)) as a colorless oil: 1H NMR
(300 MHz, C6D6) δ 5.75 (m, 1H, CHd), 4.99 (m, 2H, CH2d), 2.43 (t,
J ) 6.75 Hz, 2H, NCH2), 2.34 (t, J ) 7.05 Hz, 2H, NCH2), 2.07 (td,
3J ) 7.20 Hz, 4J ) 2.70 Hz, 2H, CH2Ct), 1.98 (m, 2H, CH2), 1.77 (t,
4J ) 2.70 Hz, 1H, HCt), 1.46 (m, 2H), 1.37 (m, 2H), 0.46 (br, 1H,
NH); 13C NMR (75 MHz, CDCl3) δ 139.0, 114.6, 84.4, 68.8, 49.4,
46.7, 31.8, 29.8, 29.3, 16.4; MS (rel abundance) M+ (12), M+ - 1 (5),
M+ + 1 (2), 136.2 (7), 123.2 (19), 108.2 (10), 96.1 (100), 83.1 (9),
69.1 (19), 55.1 (100, 41.1 (15); high-resolution mass spectrum, calcd
for C10H17N (M+) 151.1361, found 151.1356.
(c) 7-Phenylhept-6-yn-1-amine (13). 13 was prepared by a method
similar to that for 1 except that the reaction mixture was refluxed for
2 days. After distillation (169-170 °C (11 mmHg)), 7.7 g (28% yield)
of H2N(CH2)5CtCPh was obtained: 1H NMR (300 MHz, CDCl3) δ
7.39 (m, 2H, Ph), 7.26 (m, 3H, Ph), 2.71 (t, J ) 6.24 Hz, 2H, CH2N),
2.41 (t, J ) 6.98 Hz, 2H, CH2CtC), 1.84 (br s, 2H, NH2), 1.62 (m,
2H, CH2CH2N), 1.49 (m, 4H, 2CH2); 13C NMR (75 MHz, 1H-decoupled,
CDCl3) δ 131.5 (CH), 128.1 (CH), 127.5 (CH), 123.8 (C of Ph), 90.1
(CC), 80.6 (CC), 42.0 (CH2N), 33.1 (CH2), 28.5 (CH2), 26.1 (CH2),
19.3 (CH2); 13C NMR (75 MHz, 1H-coupled, CDCl3) δ 130.8 (d, CH),
127.5 (d, CH), 126.9 (d, CH), 123.4 (s, C of Ph), 89.6 (s, CtC), 80.1
(s, CtC), 41.4 (t, JCH ) 132 Hz, CH2N), 32.6 (t, JCH ) 125 Hz, CH2),
27.9 (t, JCH ) 128 Hz, CH2), 25.5 (t, JCH ) 126 Hz, CH2), 18.7 (t, JCH
) 129 Hz, CH2); IR (CHCl3) 2233, 1599 cm-1; MS (rel abundance)
M+ (98), M+ - 1 (18), M+ + 1 (32), 170.1 (27), 158.1 (52), 141.1
(43), 128.1 (62), 115.0 (85), 91.0 (31), 82.1 (36), 56.0 (100), 43.0 (19);
high-resolution mass spectrum, calcd for C13H17N(M+) 187.1361, found
187.1359.
Compound 13 was dissolved in dry diethyl ether; then hydrogen
chloride gas was bubbled into the solution to form a colorless
precipitate. After filtration, the solid was washed with dry diethyl ether
and recrystallized from an EtOH/ethyl acetate mixture to given
HCl‚H2N(CH2)5CtCPh‚2H2O: 1H NMR (300 MHz, D2O) δ 7.24 (m,
2H, Ph), 7.16 (m, 3H, Ph), 2.79 (t, J ) 7.41 Hz, 2H, CH2N), 2.24 (t,
J ) 6.83 Hz, 2H, CH2CtC), 1.40 (m, 6H, 3CH2). Anal. Calcd for
C13H18NCl‚2H2O: C, 60.10; H, 8.53; N, 5.39. Found: C, 59.80; H,
7.13; N, 5.41.
Synthesis of N-Allyl-5-(trimethylsilyl)-4-pentyn-1-amine (15). A
solution of 40.0 g (0.39 mol) of ClCH2CH2CH2CtCH in 200 mL of
THF was treated with 0.39 mol of n-BuLi at -78 °C over a period of
30 min. The reaction mixture was stirred for 1.5 h at -78 °C, warmed
to room temperature for 2 h, and then refluxed for 2h. Next, the reaction
mixture was cooled to -78 °C, 42.5 g (0.39 mol) of ClSiMe3 was
syringed into the solution over a period of 10 min, and the mixture
was stirred at -78 °C for an additional 2 h, warmed to room
temperature, stirred for 2 h, and then refluxed for 2 h. The mixture
was next cooled to room temperature, and 150 mL of water was added
to the solution. After separation of the organic and aqueous phases,
the aqueous phase was extracted with 100 mL of CHCl3. The combined
organic phase and CHCl3 extract was washed with 150 mL of saturated
NaCl and then dried over MgSO4 overnight. Removal of the solvent
by rotary evaporation followed by distillation gave 57.8 g (85% yield)
of Me3SiCtCCH2CH2CH2Cl: 1H NMR (300 MHz, CDCl3) δ 3.63 (t,
J ) 6.45 Hz, 2H, ClCH2), 2.39 (t, J ) 6.75 Hz, 2H, tCCH2), 1.94 (m,
2H, CH2), 0.13 (s, 9H, SiMe3).
A mixture of 10.0 g (0.057 mol) of 1-chloro-5-(trimethylsilyl)-4-
pentyne and 35.0 g (0.60 mol) of allylamine in 0.3 g of NaI was sealed
in a storage tube and heated at 60 °C for 7 days. After the reaction
solution had cooled to room temperature, it was poured into a separatory
funnel containing 100 mL of H2O. The aqueous phase was then
separated and extracted with 3 × 50 mL of diethyl ether. The combined
extracts and the organic phase were washed with 70 mL of brine, dried
over MgSO4, and concentrated by rotary evaporation. Distillation
(143-145 °C (55 mmHg)) gave 6.1 g (55% yield) of Me3SiCtCCH2-
CH2CH2NHCH2CHdCH2 as a colorless oil: 1H NMR (300 MHz,
CDCl3) δ 5.93-5.83 (m, 1H, CHd), 5.19-5.04 (m, 2H, CH2), 3.23
(d, J ) 5.7 Hz, 2H, NCH2CHd), 2.69 (t, J ) 7.05 Hz, 2H, NCH2),
2.27 (t, J ) 7.05 Hz, 2H, CCH2), 1.67 (m, 2H, CH2), 1.33 (br, 1H,
NH), 0.11 (s, 9H, SiMe3); 13C (75 MHz, CDCl3) δ 136.8, 115.8, 106.8,
84.9, 52.3, 48.2, 28.6, 17.8, 0.1; MS (rel abundance) M+ (5), M+ - 1
(4), M+ + 1 (1), 180.1 (38), 168.1 (7), 152.1 (9), 122.1 (95), 109.1
(7), 96.1 (6), 82.1 (14), 70.1 (100), 59.0 (14), 41.0 (38); high-resolution
mass spectrum, calcd for C11H21NSi (M+) 195.1443, found 195.1439.
Synthesis of N-Allyl-4-pentyn-1-amine (17). A mixture of 8.0 g
(0.046 mol) of 1-chloro-5-(trimethylsilyl)-4-pentyne, 43.0 g (0.75 mol)
of allylamine, and 0.3 g of NaI was sealed in a storage tube and heated
at 60 °C for 4 days. After the reaction solution cooled to room
temperature, it was poured into a separatory funnel containing 200 mL
of NaOH (10% solution). The aqueous phase was then separated and
Typical NMR-Scale Catalytic Hydroamination/Cyclization Reac-
tions. In the glovebox, the Cp′2SmCH(SiMe3)2 precatalyst (6.0 mg,
10.5 µmol) was loaded into an NMR tube equipped with a Teflon valve.
On the high-vacuum line, the NMR tube was evacuated and refilled
with argon three times. Benzene (0.2 mL) was next vacuum-transferred
into the tube, and then a mixture (0.5 mL) of benzene-d6 and
5-phenylpent-4-yn-1-amine (1, 2.60 mmol, 248-fold molar excess) was
transferred in via syringe under an argon flush while the tube was cooled
to -78 °C to seal the precatalyst under the frozen benzene. The NMR
tube was then evacuated and refilled with argon three times at -78 °C
1
and finally sealed. The ensuing reaction was monitored by H NMR.
1
The product was identified by H and 13C NMR, GC/MS, and high-
resolution mass spectrometry.
Typical Preparative-Scale Catalytic Hydroamination/Cyclization
Reactions. Scale-up catalytic reactions were carried out using the
following procedure. In the glovebox, 20.0 mg (34.5 µmol) of Cp′2-
SmCH(SiMe3)2 was loaded into a reaction vessel (25 mL) equipped
with a magnetic stir bar. Next, 2.0 mL of C6H6 was vacuum-transferred
onto the precatalyst, followed by syringing 2.0 mL of a mixture of
5-(trimethylsilyl)-4-pentyn-1-amine (9, 0.250 g, 1.62 mmol) and
benzene (1.5 mL) onto the frozen benzene and precatalyst mixture.
The mixture was then freeze-pump-thaw degassed and warmed to
room temperature. The clear yellow solution was stirred under argon
for 2 days. Anaerobic filtration of the solution followed by vacuum
transfer afforded a mixture of C6H6 and 5-[(trimethylsilyl)methyl]-3,4-
dihydro-2H-pyrrole (10). After the benzene was distilled off at
atmospheric pressure, 0.23 g (92% yield) of 10 was obtained as a
1
colorless oil. It was >95% pure by H NMR and GC/MS.

9300 J. Am. Chem. Soc., Vol. 118, No. 39, 1996
Li and Marks
2-Benzyl-1-pyrroline (2). This pyrrole derivative was synthesized
catalytically using the procedure described under typical NMR-scale
reactions. The NMR data agree with the literature data.4e,19d The yield
(>95%) was estimated by the 1H NMR spectrum and GC/MS: 1H NMR
(300 MHz, C6D6): δ 7.16-7.03 (m, 5H, Ph), 3.75 (t, J ) 7.20 Hz,
2H, CH2N), 3.55 (s, 2H, CH2Ph), 2.02 (t, J ) 8.13 Hz, 2H, CH2C )
CH2SiMe3), 1.51 (m, 2H, CH2), 0.04 (s, 9H, SiMe3); 13C NMR (75
MHz, 1H-decoupled, C6D6) δ 174.26 (CdN), 61.43 (CH2N), 39.86
(CH2CdN), 24.68 (CH2CdN), 23.48 (CH2), 1.06 (SiMe3); 13C NMR
1
(75 MHz, H-coupled, C6D6) δ 174.1 (s, CdN), 61.3 (t, JCH ) 138
Hz, CH2N), 39.8 (t, JCH ) 128 Hz, CH2CdN), 24.6 (t, JCH ) 120 Hz,
CH2SiMe3), 23.5 (t, JCH ) 130 Hz, CH2), 1.1 (q, JCH ) 118 Hz, SiMe3);
MS (rel abundance) M+ (43), M+ - 1 (28), M+ + 1 (10), 140.1 (56),
127.1 (8), 114.1 (11), 102.1 (10), 84.1 (100), 73.0 (73), 59.0 (27), 42.0
(17); high-resolution mass spectrum, calcd for C8H17NSi 155.1130,
found 155.1124.
1
N), 1.42 (m, 2H, CH2); 13C NMR (75 MHz, H-decoupled, C6D6) δ
174.9 (CdN), 137.9 (C of Ph), 129.3 (CH), 128.8 (CH), 126.6 (CH),
61.4 (CH2N), 40.8 (CH2), 36.4 (CH2), 22.9 (CH2); 13C NMR (75 MHz,
1H-coupled, C6D6) δ 175.0 (s, CdN), 138.0 (s, C of Ph) 129.4 (d, CH),
128.8 (d, CH), 126.7 (d, CH), 61.5 (t, JCH ) 138 Hz, CH2N), 40.9 (t,
JCH ) 127 Hz, CH2), 36.4 (t, JCH ) 129 Hz, CH2), 23.0 (t, JCH ) 130
Hz, CH2); MS (rel abundance) M+ (100), M+ - 1 (76), M+ + 1 (33),
144.1 (4), 130.1 (13), 117.1 (19), 91.1 (71), 84.1 (51), 68.0 (15), 54.0
(10), 42.0 (11), 41.0 (13), 39.0 (13); high-resolution mass spectrum,
calcd for C11H13N 159.1048, found 159.1042.
2-Benzyl-3,4,5,6-tetrahydropyridine (12). The procedure described
above was employed except that Cp′2SmCH(SiMe3)2 (15.0 mg, 26.0
µmol) and 9 (564.0 µmol) were used to prepare this cyclized compound.
The NMR data agree with the published data.4e,17a,19d The yield (>95%)
1
was estimated by H NMR and GC/MS: 1H NMR (300 MHz, C6D6)
δ 7.17-6.99 (m, 5H, Ph), 3.52 (m, 2H, CH2N), 3.37 (s, 2H, CH2Ph),
1.63 (m, 2H, CH2CdN), 1.13 (m, 4H, 2CH2).
2-Ethyl-1-pyrroline (4). The reaction of Cp′2SmCH(SiMe3)2 (8.7
mg, 15.0 µmol) with 3 (1.36 mmol) in benzene-d6, as described under
typical NMR-scale reactions, afforded cyclized pyrrole derivative 4.
2-Benzyl-3,4,5,6-tetrahydro-2H-azepin (14). This cyclized seven-
membered ring azepin derivative was prepared as described for 2 above
except that Cp′2SmCH(SiMe3)2 (5.6 mg, 9.7 µmol) and 13 (2.76 mmol)
were used. The NMR results agree with literature data.19b,d The yield
(>92%) was estimated by 1H NMR and GC/MS: 1H NMR (300 MHz,
C6D6) δ 7.28-7.05 (m, 5H, Ph), 3.59 (t, J ) 4.50 Hz, 2H, CH2N),
3.52 (s, 2H, CH2Ph), 1.99 (t, J ) 4.50 Hz, CH2CdN), 1.39 (m, 4H,
2CH2), 0.98 (dd, 2H, CH2); 13C NMR (75 MHz, 1H-decoupled, C6D6)
δ 175.2 (CdN) 137.0 (C of Ph), 129.7 (CH), 128.7 (CH), 126.7 (CH),
52.3 (CH2N), 49.9 (CH2), 32.5 (CH2), 31.8 (CH2), 26.9 (CH2), 24.1
(CH2); MS (rel abundance) M+ (100), M+ - 1 (82), M+ + 1 (12),
172.1 (4), 158.1 (27), 144.1 (19), 130.0 (44), 115.0 (14), 110.1 (13),
84.0 (9); high-resolution mass spectrum, calcd for C13H17N 187.1361,
found 187.1346.
1
The yield (>95%) was estimated by the H NMR spectrum and GC/
MS. The NMR data agree with the published spectra:19a,c,e,f 1H NMR
(300 MHz, C6D6) δ 3.73 (m, 2H, CH2N), 2.09 (q, J ) 7.56 Hz, 2H,
CH2CH3), 1.99 (t, J ) 8.16 Hz, 2H, CH2CdN), 1.47 (m, 2H, CH2),
1
1.09 (t, J ) 7.41 Hz, 3H, CH3); 13C NMR (75 MHz, H-decoupled,
C6D6) δ 176.89 (CdN), 61.3 (CH2N), 37.0 (CH2CdN), 27.0 (CH2-
1
CH2N), 22.9 (CH2CH3), 10.9 (CH3); 13C NMR (75 MHz, H-coupled,
C6D6) δ 176.9 (s, CdN), 61.3 (t, JCH ) 137.58 Hz, CH2N), 37.0 (t,
JCH ) 128 Hz, CH2CdN), 27.0 (t, JC ) 122 Hz, CH2CH2N), 22.9 (t,
JCH ) 130 Hz, CH2CH3), 10.8 (q, JCH ) 126 Hz, CH3); MS (rel
abundance): M+ (58), M+ - 1 (43), M+ + 1 (6) 69.1 (100), 56.1 (37),
54.0 (28); high-resolution mass spectrum, calcd for C6H11N 97.0891,
found 97.0912.
The typical preparative-scale reaction procedure described above was
used in a scale-up reaction with Cp′2SmCH(SiMe3)2 (20.0 mg, 34.5
µmol) and 3 (0.47 g, 4.85 mmol) except that the reaction mixture was
stirred for 4 days. Isolated yield: 59%.
Synthesis of 2-[(Trimethylsilyl)methylidene]-1-allylpyrrolidine
(16) and 2-[(Trimethylsilyl)methyliden]-1-(1-propenyl)pyrrolidine
(16a). Cyclized pyrrolidine derivative 16 were prepared as described
for 2 but using Cp′2LuCH(SiMe3)2 (3.1 mg, 5.0 µmol) and 15 (52.2
1
mg, 267.9 µmol). The yield (>90%) was estimated by H NMR and
GC/MS: 1H NMR (400 MHz, C6D6) δ 5.64 (m, 1H, CHd), 4.97 (m,
2H, CH2d), 3.75 (s, 1H, CH), 3.46 (d, J ) 5.64 Hz, 2H, NCH2Cd),
2.79 (t, J ) 6.68 Hz, 2H, CH2N), 2.37 (t, J ) 7.67 Hz, 2H, CH2CN),
2-(3-Methyl-3-butenyl)-1-pyrroline (6). The reaction of Cp′2-
SmCH(SiMe3)2 (10.0 mg, 17.2 µmol) with 5 (23.6 mg, 172.0 µmol) in
benzene-d6 as described under typical NMR-scale reactions afforded
cyclized pyrrole derivative 6. The yield (>95%) was estimated by
1
1.40 (m, 2H, CH2), 0.30 (s, 9H, SiMe3); 13C NMR (100 MHz, H-
1
the H NMR spectrum and GC/MS: 1H NMR (300 MHz, C6D6) δ
decoupled, C6D6) δ 158.6, 133.8, 116.0, 76.5, 51.0, 48.9, 32.1, 21.7,
1.4; MS (rel abundance) M+ (26), M+ - 1 (9), M+ + 1 (5), 180.2
(38), 152.1 (8), 136.1 (8), 122.1 (100), 108.1 (14), 84.1 (19), 73.1 (52),
59.1 (15), 41.1 (14); high-resolution mass spectrum, calcd for C11H21-
NSi 195.1442, found 195.1441.
4.77 (s, 2H), 3.76 (t, J ) 7.20 Hz, 2H), 2.33 (s, 4H), 1.98 (t, J ) 8.33
Hz, 2H), 1.63 (s, 3H), 1.46 (m, 2H); 13C NMR (75 MHz, 1H-decoupled,
C6D6) δ 175.7, 145.5, 110.3, 61.3, 37.2, 34.6, 32.1, 22.9, 22.6; MS
(rel abundance) M+ (25), M+ - 1 (22), M+ + 1 (4), 122.2 (60), 108.2
(49), 84.2 (69), 53.1 (27), 41.2 (100); high-resolution mass spectrum,
calcd for C9H15N 137.1204, found 137.1228.
Cyclized derivative 16a was synthesized in a procedure analogous
to that for 2 in the NMR-scale reaction except using 3.0 mg (4.9 µmol)
of Cp′2SmCH(SiMe3)2 and N-allyl-5-(trimethylsilyl)-4-pentyn-1-amine
(15, 17.9 mg, 92.0 µmol). The NMR and GC/MS results indicate that
16a is the major product (91%) and that two other isomers (8%) are
present, which have identical molecular masses. The yield (91%) was
2-Methyl-1-pyrroline (8). A procedure analgous to that for 2 was
used in an NMR-scale reaction for the synthesis of title pyrrole
derivative using Cp′2SmCH(SiMe3)2 (3.2 mg, 5.5 µmol) and 7 (500.3
1
µmol). The yield (>90%) was estimated by the H NMR spectrum
1
and GC/MS: 1H NMR (300 MHz, C6D6) δ 3.71 (m, 2H, CH2Cd),
1.94 (t, J ) 8.10 Hz, 2H, CH2N), 1.77 (s, 3H, CH3), 1.45 (m, 2H,
CH2); 13C NMR (75 MHz, C6D6) δ 174.4, 61.5, 38.5, 23.2, 19.4; MS
(rel abundance) M+ (69), M+ - 1 (12), M+ + 1 (8), 69.1 (16), 55.1
(100), 42.0 (61); high-resolution mass spectrum, calcd for C5H9N
83.0735, found 83.0749.
estimated by H NMR and GC/MS after vacuum transfer or volatile
products: 1H NMR (300 MHz, C6D6) δ 6.70 (d, J ) 13.7 Hz, 1H,
NCHd), 4.49 (m, 1H, dCHMe), 4.19 (s, 1H, dCH(SiMe3)), 2.91 (t,
J ) 6.8 Hz, 2H, NCH2), 2.29 (t, J ) 7.7 Hz, 2H, CH2Cd), 1.68 (d, J
) 6.6 Hz, 3H, CH3), 1.32 (m, 2H, CH2), 0.26 (s, 9H, SiMe3); 13C NMR
(75 MHz), C6D6) δ 154.6, 128.1, 100.0, 80.3, 48.3, 31.9, 21.2, 15.7,
1.1; 13C NMR (75 MHz, 1H-coupled, C6D6) δ 154.9 (s), 128.6 (d, JCH
) 157.0 Hz), 100.4 (d, JCH ) 157.7 Hz), 80.5 (d, JCH ) 132.7 Hz),
2-[(Trimethylsilyl)methyl]-1-pyrroline (10). The cyclized pyrrole
derivative was synthesized in both NMR- and preparative-scale
reactions. A procedure analogous to that for 2 was used in the NMR-
scale reaction using Cp′2SmCH(SiMe3)2 (4.0 mg, 6.9 µmol) and 9 (164.0
mg, 1059.0 µmol). The yield (>95%) was estimated from the 1H NMR
spectrum and GC/MS: 1H NMR (300 MHz, C6D6) δ 3.77 (t, J ) 7.95
Hz, 2H, CH2N), 2.07 (t, J ) 8.11 Hz, 2H, CH2C÷bN), 1.78 (s, 2H,
48.6 (t, JCH ) 137.3 Hz), 32.3 (t, JCH ) 130.3 Hz), 21.5 (t, JCH
)
131.9 Hz), 16.1 (q, JCH ) 119.4 Hz), 1.5 (q, JCH ) 117.5 Hz); MS (rel
abundance): M+ - 1 (10), M+ (73), M+ + 1 (14, 180.2 (92), 166.2
(9), 150.1 (9), 140.2 (42), 122.2 (100), 106.1 (12), 97.1 (7), 83.1 (5),
73.1 (65), 59.1 (26), 41.0 (11); high-resolution mass spectrum, calcd
for C11H21NSi 195.1443, found 195.1427.
Synthesis of 2-Methylene-1-allylpyrrolidine (18). Cyclized pyr-
rolidine derivative 18 was prepared as described for 2 above using Cp′2-
SmCH(SiMe3)2 (3.0 mg, 5.2 µmol) and 17 (32.6 mg, 169.3 µmol). The
(19) (a) Hua, D. H.; Miao, S. W.; Bharathi, S. N.; Katsuhira, T.; Bravo,
A. A. J. Org. Chem. 1990, 55, 3682-3684. (b) Hoffmann, R. V.; Buntain,
G. A. J. Org. Chem. 1988, 53, 3316-3321, and references therein. (c)
Ananthapadmanabhan, S.; Raja, T. K.; Srinivasan, V.; Simon, A. Indian J.
Chem. 1988, 27B, 580. (d) Bacos, D.; Celerier, J. P.; Lhommet, G.
Tetrahedron Lett. 1987, 28, 2353-2354. (e) Pugin, B.; Venanzi, L. M. J.
Am. Chem. Soc. 1983, 105, 6877-6881. (f) Fraser, R. R.; Banville, J.;
Akiyama, F.; Offermanns, N. C. Can. J. Chem. 1981, 59, 705-709.
1
yield (>85%) was estimated by the H NMR and GC/MS: 1H NMR
(300 MHz, C6D6) δ 5.72 (m, 1H, CHd), 5.02 (m, 2H, CH2d), 3.77 (d,
J ) 20.7 Hz, 2H, CH2dCN), 3.46 (d, J ) 5.70 Hz, 2H, NCH2CHd),
2.82 (t, J ) 6.60 Hz, 2H, CH2N), 2.36 (m, 2H, CH2CN), 1.44 (m, 2H,

Hydroamination/Cyclization of Amino Alkynes
J. Am. Chem. Soc., Vol. 118, No. 39, 1996 9301
CH2); 13C NMR (75 MHz, 1H-decoupled, C6D6) δ 152.6, 134.0, 116.0,
71.6, 51.7, 49.8, 32.0, 22.0; 13C NMR (75 MHz, 1H-coupled, C6D6) δ
152.6 (s), 134.0 (d, JCH ) 150.8 Hz), 116.0 (t, JCH ) 149.5 Hz), 71.6
(t, JCH ) 156.3 Hz), 51.7 (t, JCH ) 134.2 Hz), 49.8 (t, JCH ) 128.2
Hz), 32.0 (t, JCH ) 132.7 Hz), 22.0 (t, JCH ) 134.2 Hz); MS (rel
abundance) M+ (77), M+ - 1 (100), M+ + 1 (8), 108.1 (25), 96.1
(25), 80.1 (21), 67.1 (19), 54.1 (31), 41.1 (51); high-resolution mass
spectrum, calcd for C8H12N(M+ - H) 122.0970, found 122.0963.
Synthesis of 2-[(Trimethylsilylmethylidene]-1-(4-pentenyl)pyr-
rolidine (20). The reaction of Cp′2SmCH(SiMe3)2 (3.0 mg, 5.1 µmol)
with N-4-pentenyl-5′-(trimethylsilyl)-4′-pentyn-1-amine (19, 81.2 mg,
364.0 µmol) in benzene-d6 was carried out as described for 2 and
afforded the cyclized pyrrolidine derivative 20 (90% yield): 1H NMR
(300 MHz, C6D6) δ 5.64 (m, 1H, CHdCH2), 4.91 (m, 2H, CH2d),
3.70 (s, 1H, dCH(SiMe3), 2.86 (t, J ) 7.35 Hz, 2H, NCH2CH2CH2-
CHdCH2), 2.74 (t, J ) 6.75 Hz, 2H, NCH2), 2.36 (t, J ) 7.65 Hz,
CH2Cd), 1.81 (m, 2H, CH2CHd), 1.43 (m, 2H, NCH2CH2CH2Cd),
1.37 (m, 2H, CH2), 0.28 (s, 9H, SiMe3); 13C NMR (75 MHz, C6D6) δ
159.0, 138.4, 114.9, 75.6, 51.4, 45.7, 32.3, 31.7, 26.1, 21.8, 1.5; MS
(rel abundance) M+ - 1 (18), M+ (16), M+ + 1 (5), 208.2 (19), 182.2
(10), 168.2 (40), 155.2 (24), 140.1 (29), 123.1 (18), 110.1 (14), 98.1
(46), 73.1 (100), 59.1 (14), 44.1 (30); high-resolution mass spectrum,
calcd for C12H22NSi (M+ - Me) 208.1522, found 208.1495.
sensitivity, kinetics, and mechanism of the organolanthanide-
catalyzed intramolecular hydroamination/cyclization of ami-
noalkynes. This study represents an extension of, and com-
parison to, our previous investigation of the catalytic hydro-
amination/cyclization of unprotected aminoolefins.7c-g In the
ensuing discussion, we focus on reaction scope, alkyne sub-
stituent effects on the reaction, metal ion size and ancillary
ligand effects on the reaction, and kinetics and the rate law.
Reaction and Scope of Hydroamination/Cyclization. The
organolanthanides Cp′2LnCH(SiMe3)2 and Me2SiCp′′2LnCH-
(SiMe3)2 efficiently and regiospecifically catalyze the intramo-
lecular hydroamination/cyclization of a variety of aliphatic and
aromatic aminoalkynes to yield the corresponding heterocycles
1
(Table 1). The reactions are conveniently monitored by H
NMR spectroscopy. The initial reaction of Cp′2LnCH(SiMe3)2
and Me2SiCp′′2LnCH(SiMe3)2 complexes with aminoalkynes
quantitatively generates lanthanide amides (presumably amine-
amide complexes of the type Cp′2LnNHR(H2NR)x/Me2SiCp′′2-
LnNHR(H2NR)x)7c,d and CH2(SiMe3)2 (within seconds as moni-
tored by 1H NMR; Scheme 2). The mechanism of this process
likely involves a four-centered protonolytic transition state.20
Hydroamination/cyclization of primary aminoalkynes yields
enamines, which subsequently and expectedly undergo tau-
tomerization to the more stable imines21 at room temperature
(eq 2). The intermediate enamines are in some cases observable
Synthesis of 2-Methylene-1-(4-pentenyl)pyrrolidine (22). This
cyclized pyrrolidine derivative was prepared as described for 2, but
using Cp′2SmCH(SiMe3)2 (1.0 mg, 1.7 µmol) and 21 (8.0 mg, 53.1
µmol): 1H NMR (400 MHz, C6D6) δ 5.74 (m, 1H, CHd), 4.98 (m,
2H, CH2d), 3.76 (d, J ) 25.5 Hz, 2H, CH2dCN), 2.88 (d, J ) 7.20
Hz, 2H), 2.79 (t, J ) 6.00 Hz, 2H), 2.38 (m, 2H), 1.90 (m, 2H), 1.59-
1.42 (m, 4H); 13C NMR (100 MHz, 1H-decoupled, C6D6) δ 152.9, 138.5,
114.8, 70.7, 51.9, 46.5, 32.2, 31.7, 26.1, 22.1; 13C NMR (100 MHz,
1H-decoupled, C6D6) δ 152.9 (s), 138.5 (d, JCH ) 146.4 Hz), 114.9 (t,
JCH ) 154.4 Hz), 70.7 (t, JCH ) 156.3 Hz), 51.9 (t, JCH ) 138.4 Hz),
1
by H NMR spectroscopy during the course of the reactions.
46.5 (t, JCH ) 130.5 Hz), 32.3 (t, JCH ) 131.2 Hz), 31.7 (t, JCH
)
Not surprisingly, the cyclization of secondary amines results
only in enamines.
122.9 Hz), 26.1 (t, JCH ) 127.8 Hz), 22.1 (t, JCH ) 129.4 Hz); MS (rel
abundance) M+ (13), M+ - 1 (4), M+ + 1 (2), 136.2 (6), 123.2 (23),
108.2 (9), 96.1 (100), 82.1 (8), 69.1 (21), 55.1 (18), 41.1 (29); high-
resolution mass spectrum, calcd for C10H17N 151.1361, found 151.1352.
As in the case of organolanthanide-catalyzed hydroamination/
cyclization of aminoolefins,7c-g the reaction of Cp′2NdCH-
(SiMe3)2, Cp′2SmCH(SiMe3)2, and Me2SiCp′′2SmCH(SiMe3)2
with aminoalkynes effects distinctive color changes associated
with catalytic initiation and termination. Thus, the original green
and orange solutions of the Nd and Sm hydrocarbyl precatalysts,
respectively, in C6D6 or C7D8 instantaneously turn to the
characteristic blue and yellow colors of the corresponding
amine-amide complexes7c,d in conjunction with the initiation
of catalytic turnover. Upon consumption of the aminoalkynes,
the resulting reaction solutions revert to the original colors. In
the presence of the paramagnetic Nd3+ (4 f3) and Sm3+ (4 f5)
catalysts, only paramagnetically broadened amine product and
substrate 1H NMR resonances are detected during catalytic
turnover at room temperature. This behavior is analogous to
that observed during aminoolefin hydroamination/cyclization
and can be associated with rapid intramolecular exchange of
bound amine and amide groups as well as intermolecular
exchange of bound and free amine (substrate and product)
groups involving complexes of the type Cp′2LnNHR(NH2R)x.7c,d
The present tetrahydropyrrole, pyrroline, and pyrrolidine
products were characterized by 1H and 13C NMR spectroscopy,
GC/MS, and high-resolution mass spectroscopy and/or by
comparison with literature 1H/13C NMR spectral data and data
for independently synthesized product samples (see Experimen-
1
The yield (>85%) was estimated by the H NMR spectrum and GC/
MS.
Kinetic Studies of Hydroamination/Cyclization. In a typical
experiment, an NMR sample was prepared as described under typical
NMR-scale catalytic reactions but the NMR tube was maintained at
-78 °C until kinetic measurements were initiated. Before the measure-
ments, the NMR probe was equilibrated to the appropriate temperature
(T ( 0.2 °C; checked with a methanol or ethylene glycol temperature
standard), and the NMR sample was quickly warmed with shaking for
∼8 s and inserted into the probe. Data were acquired using four or
eight scans per time interval with a long pulse delay to avoid saturation
of the signal. The kinetics were usually monitored by the intensity
changes in the substrate resonances over three or more half-lives. The
substrate concentrations (C) were measured from the area (As) of the
1H-normalized NCH2 signals, standardized to the area (Al) of free CH2-
(SiMe3)2 in the solution, which is quantitatively generated by reaction
of the precatalysts with amines (Schemes 1 and 2). All the data
collected could be convincingly fit over approximately three half-lives
(R > 0.98) by least squares to eq 1, where C0 (C0 ) As0/Al0) is the
mt ) (C0 - C)
(1)
initial concentration of substrate (relative to precatalyst) and C (As/Al)
is the substrate concentration at time, t.
The ratio of the catalyst to substrate was accurately measured from
the ratio of As0 and Al0, or from the area of product and Al. The exact
concentrations of catalysts and substrates were determined by internal
FeCp2 calibration. The turnover frequency (Nt, h-1) was calculated
from the least-squares determined slope (m) of the resulting plot.
Typical initial substrate concentrations were in the range 0.1-4.6 M,
and typical catalyst concentrations were in the range 1.5-35 mM.
1
tal Section for details). The H NMR spectra show that the
aminoalkyne substrates are quantitatively and regiospecifically
(20) (a) Piers, W. E.; Shapiro, P. J.; Bunel, E. E.; Bercaw, J. E. Synlett
1990, 74-84. (b) Thompson, M. E.; Baxer, S. M.; Bulls, A. R.; Burger,
B. J.; Nolan, M. C.; Santarsiero, B. D.; Schaefer, W. P.; Bercaw, J. E. J.
Am. Chem. Soc. 1987, 109, 203-219. (c) Doherty, N. M.; Bercaw, J. E.
J. Am. Chem. Soc. 1985, 107, 2670-2682.
Results
The goal of this investigation was to examine the scope,
stereoselectivity, lanthanide ion sensitivity, ancillary ligand
(21) Shainyan, B. A.; Mirskova, A. N. Russ. Chem. ReV. 1979, 48, 107-
117, and references therein.

9302 J. Am. Chem. Soc., Vol. 118, No. 39, 1996
Li and Marks
Table 1. Intramolecular Hydroamination/Cyclization Results
entry
substrate
product
Nt, h-1 (°C)
yield (%)
95d
H2N
N
77 (21)a
2830 (60)a
2 (21)b
2
1
1
Ph
Ph
N
96 (21)a
28 (21)b
95d
59e
H2N
2
4
3
H2N
N
3
4
5
20 (21)a
95d
6
90d
47e
H2N
N
580 (21)a
8
7
H2N
N
95d
92e
>7600 (21)a,d
5
6
7
10
9
Me3Si
Ph
Me3Si
H2N
N
4 (21)a
328 (60)a
95d
12
14
11
Ph
H2N
0.11 (60)a
0.03 (60)b
N
92d
90d
Ph
13
15
Ph
56 (21)c
27 (21)a
N
HN
16
8
9
Me3Si
Me3Si
HN
85d
52e
N
18
17
129 (21)a
47 (21)a
90d
85d
N
HN
20
10
11
19
Me3Si
Me3Si
N
HN
22
21
a Cp′2SmCH(SiMe3)2 as precatalyst. b Me2SiCp′′2SmCH(SiMe3)2 as precatalyst. c Cp′2LuCH(SiMe3)2 as precatalyst; see text. d NMR scale reaction
1
and the yield determined by H NMR spectroscopy and GC/MS. e Preparative-scale reaction and isolated yield.
converted to the cyclized compounds shown in Table 1 with
negligible traces of starting materials or other byproducts.
General product isolation procedures involve high-vacuum
transfer of the products and other volatiles, followed by removal
of solvents and CH2(SiMe3)2. Preparative-scale reactions were
carried out in the storage tubes with products isolated in 59-
92% yields (Table 1). All the products in NMR or preparative-
scale reactions were >95% pure by GC/MS.
Table 1 presents the results of the organolanthanide-catalyzed
aminoalkyne cyclizations. The present process is capable of
regiospecifically forming five-, six-, and seven-membered
heterocycles from substrates having several classes of substit-
uents on the acetylenic moiety. The transformations 15 f 16,
17 f 18, 19 f 20, and 21 f 22 indicate that the hydroami-
nation/cyclization is not limited to primary amines and that
secondary amines also undergo rapid cyclization. The present
process is effective in the cyclization of both internal alkynes
(entries 1-3, 5-8, and 10) and terminal alkynes (entries 4, 9,
and 11). The catalytic process is also applicable to alkynes
substituted with a number of functional groups, such as alkyl
(3), allyl (5), phenyl (1, 11, 13), H (7, 17, 21), and trimethylsilyl
(9, 15, 19). This catalytic process exhibits similar efficiencies
for N-allyl- (15, 17) and N-alkenyl- (19, 21) substituted
secondary amines in the synthesis of 2-methylidenepyrrolidine
derivatives (entries 8-11).
In regard to turnover frequency, the present cyclizations are
∼10-100× more rapid than the corresponding aminoolefin
transformations for the same catalyst, temperature, and reaction
conditions.7d Indeed, Nt for process 9 f 10 considerably
exceeds the rate that can be accurately measured at room
temperature. Furthermore, in direct competition studies it can
be seen that the Ln-N bond preferentially adds to the 4-alkyne
functionality rather than to the 4-alkene in the hydroamination/
cyclization of 21 f 22 (eq 3).
As in the case of aminoolefin cyclization, the present ring-
size dependence of cyclization rates is 5 > 6 . 7, consistent
with classical, stereoelectronically controlled cyclization
processes.7d,22 A preference for a quasi-seven-membered transi-
tion state (e.g., A) is in accord with the aforementioned ring-
size effects and earlier stereochemical observations on organo-
lanthanide-catalyzed intramolecular aminoolefin hydroamination/
cyclization.7c,d In regard to the possible formation of three-

Hydroamination/Cyclization of Amino Alkynes
J. Am. Chem. Soc., Vol. 118, No. 39, 1996 9303
Table 2. Substituent Group Effects on the Turnover Frequencies
for Primary Aminoalkyne Hydroamination/Cyclizationa
N
R
R
NH2
R
Nt, h-1 b (at 21 °C)
membered rings, the preferences for five-membered-ring formation
observed in transformations of 15 f 16 and 17 f 18 (e.g., eq
4) are presumably due, among other factors, to unfavorable strain
CH2dCMeCH2
Ph
CH3
H
Me3Si
20
77
96
580
7600
a Using Cp′2SmCH(SiMe3)2 as the precatalyst. b Turnover frequencies
measured in C6D6.
Table 3. Metal Size and Ancillary Ligation Effects on the
Turnover Frequencies for Primary Aminoalkyne Hydroamination/
Cyclization
energies in the product three-membered rings.
Substituent Effects on the Catalytic Process. The kinetic
and mechanistic studies of the Cp′2Ln-catalyzed hydroamination/
cyclization process to be discussed below argue that the
turnover-limiting step is intramolecular alkyne insertion into the
Ln-N bond followed by rapid protonolysis of the resulting
Ln-C bond (Schemes 1 and 2). The transition states involved
in this process should therefore be electronically and sterically
sensitive to the environment of the insertive transition state (e.g.,
A). In an effort to investigate such effects, a study of the
turnover frequency as a function of alkyne substituent groups
was undertaken. Table 2 shows that, for similar primary
aminoalkynes, Nt is rather sensitive to the identity of the R group
on the alkyne moiety. Thus, when R ) SiMe3, a very large Nt
value is observed (9 f 10), despite the considerable steric
encumbrance of this group. This substituent kinetic effect is
in accord with proposed transition state electronic demands (B)
N
H
NH2
catalyst
ionic radiusa (Å)
Nt, h-1 (at 21 °C)
Me2SiCp′′2Nd-
Cp′2La-
1.109
1.160
1.109
1.079
0.977
78
135
207
580
711
Cp′2Nd-
Cp′2Sm-
Cp′2Lu-
a Eight-coordinate ionic radii from ref 25.
ionic radius25 and opening the metal coordination sphere by
connecting the ancillary ligands (Cp′2Ln f Me2SiCp′′2Ln or
Me2SiCp′′(R*Cp)Ln)18a,7c increase turnover frequencies, pre-
sumably reflecting significant steric demands in the insertive
transition state.7c,d,14j,18a Interestingly, and in marked contrast
to the olefin cyclization,7c,d for constant substrate and reaction
conditions, the present kinetic results for the Cp′2Ln-catalyzed
transformation 7 f 8 (Table 3) evidence increasing Nt values
on proceeding from the largest eight-coordinate ionic radius
lanthanide ion, La (1.160 Å), to intermediate Nd (1.109 Å),
Sm (1.079 Å), to smallest, Lu (0.977 Å). Furthermore,
replacement of Cp′2Nd with the more open Me2SiCp′′2Nd
catalyst also effects a decrease in Nt from 207 to 78 h-1 for the
transformation 7 f 8. The same ancillary ligand reactivity
effects are also observed in the five- and seven-membered-ring
closures of phenyl-substituted aminoalkynes (Table 1, entries
1 and 7). Thus, the organolanthanide-catalyzed cyclization of
aminoalkynes experiences a deceleration rather than an ac-
celeration or identity in rate when larger ionic radius Ln3+
catalysts or more open Me2SiCp′′2Ln coordination spheres are
employed.
since silyl functionalities are known to stabilize R-carbanions
and â-carbocations.23,24
In the case of R ) H, the appreciable Nt may reflect minimal
steric impediment of alkyne insertion into the Ln-N bond (7
f 8). Comparing these kinetic results to those for 1 f 2, 3 f
4, and 5 f 6 suggests that steric effects may be somewhat more
important than electronic ones since for Nt(R), H > Me g Ph
> 2-propenyl. For more encumbered secondary amines, the
silyl accelerating effect is not as dramatic (compare entries 8
vs 9 and 10 vs 11). The kinetic results in Tables 1 and 2
therefore likely reflect subtle combinations of R- and N-centered
electronic and steric effects.
Kinetic Studies of Aminoalkyne Hydroamination/Cycliza-
tion. A kinetic study of the 3 f 4 transformation was
1
undertaken by in situ H NMR spectroscopy. The reaction of
Metal and Ancillary Ligation Effects on the Catalytic
Process. In the case of organolanthanide-catalyzed hydroami-
nation/cyclization of aminoolefins,7c,d both increasing the Ln3+
a 40-50-fold molar excess of 5-methyl-4-pentyn-1-amine with
Cp′2SmCH(SiMe3)2 was monitored with constant catalyst
concentration until complete substrate consumption. The disap-
pearance of CH2N (δ ∼2.8 ppm) 1H resonances was normalized
to the CH2(SiMe3)2 signal as an internal standard. The turnover
frequency of cyclization was calculated from the slope of the
kinetic plots of substrate to catalyst ratio vs time. The kinetic
plots as shown in Figure 1 reveal a linear dependence of
aminoalkyne substrate concentration on reaction time over a
∼10-fold substrate concentration range, which indicates an
essentially zero-order dependence of the catalytic rate on
substrate concentration under these conditions, in analogy to
organolanthanide-catalyzed aminoolefin cyclization.7c,d This
(22) (a) Carey, F. A.; Sundberg, R. J. AdVanced Organic Chemistry; 2nd
ed., Plenum: New York, 1984; Part A, Chapter 3.9. (b) DeTar, D. F.;
Luthra, N. P. J. Am. Chem. Soc. 1980, 102, 4505-4512. (c) Mandolini, L.
J. Am. Chem. Soc. 1978, 100, 550-554. (d) Brown, R. F.; van Gulik, N.
M. J. Org. Chem. 1956, 21, 1046-1049.
(23) For discussions of the unusual aspects of d0 metal-silylvinyl
electronic structure and bonding see: (a) Horton, A. D.; Orpen, A. G.
Organometallics 1991, 10, 3910-3918. (b) Koga, N.; Morokuma, K. J.
Am. Chem. Soc. 1988, 110, 108-112. (c) Eisch, J. J.; Piotrowski, A. M.;
Brownstein, S. K.; Gabe, E. J.; Lee, F. L. J. Am. Chem. Soc. 1985, 107,
7219-7220.
(24) (a) Bassindale, A. R.; Taylor, P. G. In The Chemistry of Organic
Silicon Compounds; Patai, S., Rappaport, Z., Eds.; Wiley: Chichester, U.K.,
1989; Chapter 14. (b) Fleming, I. In ComprehensiVe Organic Chemistry;
Jones, N. D., Ed.; Pergamon Press: Oxford, U.K., 1979; Chapter 13.
(25) Shannon, R. D. Acta Crystallogr. 1976, A32, 751-760.

9304 J. Am. Chem. Soc., Vol. 118, No. 39, 1996
Li and Marks
Figure 3. Normalized ratio of aminoalkyne to lanthanide concentration
as a function of time and temperature for the intramolecular hydroami-
nation/cyclization of H2NCH2CH2CH2CtCH (7 f 8) using the
precatalyst Cp′2SmCH(SiMe3)2 in toluene-d8. Starting amine and
catalyst concentrations are identical in each experiment. The lines are
least-squares fits to the data points.
Figure 1. Plot of H2NCH2CH2CH2CtCMe concentration as a function
of time for the hydroamination/cyclization of H2NCH2CH2CH2CtCMe
(3 f 4) using Cp′2SmCH(SiMe3)2 as the precatalyst in benzene-d6 at
21 °C. The deviation from linearity at high conversions likely reflects
product inhibition (see text).
Figure 4. Eyring plot for the intramolecular hydroamination/cyclization
of H2NCH2CH2CH2CtCH (7 f 8) using the precatalyst Cp′2SmCH-
(SiMe3)2 in toluene-d8. The line represents the least-squares fit to the
data points.
Figure 2. Determination of reaction order in lanthanide concentration
for the hydroamination/cyclization of H2NCH2CH2CH2CtCMe (3 f
4) mediated by Cp′2SmCH(SiMe3)2 as the precatalyst in benzene-d6 at
21 °C.
(Figure 3). The derived ∆Hq and ∆Sq values from an Eyring
analysis (Figure 4) are 10.7(8) kcal mol-1, and -27.4(6) eu,
respectively.
result is consistent with a similar turnover-limiting step involving
intramolecular CtC insertion into the LnsN bond followed
by rapid protonolysis of the resulting LnsC bond. Considering
the rapidity of LnsC protonolysis by amines in these systems,
it seems unreasonable that intramolecular (or intermolecular)
proton transfer could be turnover-limiting under most catalytic
conditions. It is also observed (Figure 1) that the rate of
aminoalkyne cyclization begins to decrease (depart from zero-
order behavior) as the catalytic reaction progresses to g90%
completion, which is consistent with previously analyzed
examples in aminoolefin hydroamination of competitive inhibi-
tion of substrate coordination/cyclization by the product het-
erocycle as high product concentrations are attained.7c,d
When the initial concentration of the aminoalkyne is held
constant and the concentration of catalyst precursor is varied
over a 50-fold concentration range (Figure 2), a plot of reaction
rate vs precatalyst concentration indicates the reaction to be the
first-order in catalyst. Taken together, the empirical rate law
for the organolanthanide-catalyzed hydroamination/cyclization
3 f 4 is given by eq 5, which is identical to the aminoolefin
cyclization rate law.7c,d
Discussion
Catalytic Reaction Scope and Mechanism. The present
catalytic results for aminoalkyne hydroamination/cyclization
demonstrate that a substantial range of substrates can be cyclized
to the corresponding heterocycles, including not only primary
and secondary amines but also internal and terminal alkynes.
Five-, six-, and seven-membered heterocycles with several
classes of substituents R to the acetylenic moiety can be
regiospecifically synthesized by the present catalytic process.
With regard to rate, the present process exhibits significant rate
enhancements over aminoolefin cyclization.7c,d For example,
comparison of 4-pentyn-1-amine cyclization to that of 4-penten-
1-amine under identical reaction conditions using Cp′2SmCH-
(SiMe3)2 as the precatalyst reveals that Nt increases ∼100× (Nt
) 6 h-1 vs 580 h-1, respectively; eqs 6 and 7). The activation
ν ) k[substrate]0[Sm]1
(5)
The derived rate constant for the 3 f 4 conversion at 21 °C
is k ) 0.011(2) s-1. The terminal aminoalkyne cyclization 7
f 8 catalyzed by Cp′2Sm exhibits a similar kinetic independence
of amine concentration over a 0-35 °C temperature range

Hydroamination/Cyclization of Amino Alkynes
J. Am. Chem. Soc., Vol. 118, No. 39, 1996 9305
Scheme 3. A Plausible Pathway for the Organolanthanide-
Catalyzed Coupling Reactions of Terminal Alkynes
quantities of alkyne coupling products are therefore not ob-
served.27 However, in cases where alkyne or olefin function-
alities are “tethered” to the reaction center, as in recently
described bicyclizations involving difunctional amines,7a incipi-
ent metal-carbon bonds can be insertively intercepted.
In contrast to our recently reported aminoalkene-eyne
bicyclizations mediated by organolanthanides,7a attempts to
effect bicyclization of terminal alkene-enes 15 and 17 to the
corresponding pyrrolizidine derivatives (e.g., eq 9), were
unsuccessful (entries 8 and 9). This is presumably due to the
unfavorable strain in the bicyclic cyclopentene which would
form and competing protonolysis of the metal-alkenyl inter-
mediate (C) by substrates containing active hydrogen in NH
and/or tCH moieties. In the case of Cp′2SmCH(TMS)2 as the
precatalyst for 15 f 16, isomerization of the allylic double bond
is also detected7a (see Experimental Section for details).
Isomerization is not observed with smaller Cp′2LuCH(TMS)2
as the precatalyst.
energetics for the 7 f 8 conversion of ∆Hq ) 10.7(8) kcal/
mol and ∆Sq ) -27.4(6) eu can be compared to ∆Hq ) 12.7-
(1.4) kcal/mol and ∆Sq ) -27.0(4.6) eu for the aminoolefin
process in eq 6.7d While the aminoalkyne hydroamination/
cyclization has a substantially lower activation enthalpic barrier,
it appears from ∆Sq that eqs 6 and 7 proceed with similar overall
degrees of entropic reorganization on approaching the transition
state.
The present kinetic results doubtless reflect the differing
insertive reactivities of the CdC and CtC multiple bonds. This
hypothesis is further supported by the results in the previous
section showing that the competitive transformation 21 f 22
favors aminoalkyne rather than aminoolefin ring closure (eq 3).
An appealing explanation for the preferential insertion into
Ln-N bonds of alkyne over olefinic functionalities involves
the sterically more accessible, cylindrical CtC π system, the
more nucleophilic sp-hybridized carbon atoms,26 the greater
CtC π-donating capacity, the greater thermodynamic driving
force,10 and possibly the greater electronic stabilization of the
four-center transition state (B).
With regard to substrates, the present process is able to effect
hydroamination/cyclization of both internal and terminal alkyne
functionalities. An interesting contrast is presented by other
organo-f-element-catalyzed alkyne reactions. Thus, Teuben and
co-workers have reported Cp′2LnCH(SiMe3)2-catalyzed terminal
alkyne dimerization and/or oligomerization processes which
doubtless proceed via initial protonolysis to yield LnsCtCR
species which then undergo subsequent CtC insertion to
generate metal-alkenyl complexes. Further alkyne insertion
competes with intermolecular RCtCH protonolysis to yield
alkene-alkyne dimers or trimers (Scheme 3).8b-g In addition,
Eisen and co-workers recently reported analogous terminal
alkyne dimerization and oligomerization processes mediated by
organoactinides (eq 8; An ) Th, U).8a
The previous mechanistic studies of organolanthanide-
catalyzed aminoolefin hydroamination/cyclization argued that
olefin insertion into the Ln-N bond is the turnover-limiting
step and that this is followed by rapid intra- and intermolecular
Ln-C protonolysis, affording the product heterocycle and
regenerating the metal-amide catalyst.7c,d In the present
aminoalkyne hydroamination/cyclization processes, the catalytic
results derived from the kinetic data, as well as substrate
substituent, metal ion size, and ancillary ligand effects on the
turnover frequency, argue for a basically similar mechanistic
picture. The catalyst precursors Cp′2LnCH(SiMe3)2 react rapidly
with aminoalkynes in benzene-d6 or toluene-d8 to form CH2-
(SiMe3)2 (used as an internal NMR standard) and the putative,
catalytically active Cp′2LnNR(CH2)nCtCR′[HNR(CH2)nCtCR′]x
species (R ) H, alkyl; R′ ) H, phenyl, alkyl, trimethylsilyl).
This species undergoes bound amine-amide exchange and/or
bound-free amine substrate or product exchange, which is rapid
on the NMR time scale during catalytic turnover at room
temperature and above. Analogous species were identified in
variable-temperature NMR studies of aminoolefin hydroami-
nation/cyclization,7c and one was characterized crystal-
lographically.7d A reasonable, minimal scenario for the present
catalytic mechanism is depicted in Scheme 2. Turnover-limiting
insertion of alkyne into the Ln-N bond would be followed by
rapid intramolecular or intermolecular protonolysis of the
resulting Ln-C bond, which would afford tautomerizable (eq
2) enamines and regenerate Cp′2Ln-NR(CH2)nCtCR′ species.
Substituent, Metal, and Ancillary Ligation Effects on the
Catalytic Process. As discussed above, the turnover frequen-
cies for the organolanthanide-catalyzed cyclization of variously
substituted aminoalkynes exhibit marked substituent effects
under constant catalyst and reaction conditions. For 4-pentynyl
substrates, Nt decreases in the order SiMe3 > H > CH3 g Ph
> CH2dCMeCH2. For the sterically bulky, but transition state-
The present results, and those on intermolecular alkene and
alkyne hydroamination to be discussed elsewhere,7b,15b argue
that rapid N-H protonolysis of incipient metal-carbon bonds
limits the lifetimes/effective concentrations of the metal-alkynyl
and -alkenyl species shown in Scheme 3, and significant
(27) For a terminal acetylene, the reaction with a Cp′2LnNHR complex
to yield a Cp′2LnCtCR complex and H2NR is estimated from thermo-
chemical data11-13 to be slightly exothermic by ∼7 kcal/mol. Apparently
this pathway is not competitive with the far more exothermic insertion of
the acetylene into the Ln-N bond.
(26) For a comparison of nucleophilic additions to alkenes and alkynes,
see for example: Lowry, T. H.; Richardson, K. S. Mechanism and Theory
in Organic Chemistry 3rd ed.; Harper & Row: New York, 1987; Chapter
7, and references therein.

9306 J. Am. Chem. Soc., Vol. 118, No. 39, 1996
Li and Marks
stabilizing SiMe3 group, the turnover frequency is J7600 h-1
at room temperature using Cp′2SmCH(SiMe3)2 as the precatalyst
(Table 1, entry 5), while Nt decreases to 580 h-1 for less
sterically encumbered and less electronically distinctive 4-pen-
tyn-1-amine. A similar but less dramatic decline in rate is
observed in the cyclization of secondary amines, where the
turnover frequency decreases from 56 to 27 h-1 (Table 1, entries
8 and 9) and from 129 to 47 h-1 (Table 1, entries 10 and 11)
upon changing the substituent from SiMe3 to H. For sterically
and electronically less distinctive substituents such as Ph and
alkyl (CH3, CH2dCMeCH2), steric impediments appear to have
an important effect on the cyclization rates, suggesting a
combination of intrasubstrate-based steric encumbrance to
cyclization within the metal coordination sphere, electronic
stabilization of the transition state, and differing steric interac-
tions between substituted alkynyl groups and the metal ancillary
ligands.
In the case of aminoolefin cyclization, the reaction rates
increase with increasing Ln ionic radius and more “open”
lanthanide coordination spheres.7c,d An analogous enhancement
with large metal ions and more open coordination spheres has
also been observed for organo-f-element-mediated olefin
hydrosilylation,14c,d hydrophosphination,7e olefin hydrogen-
ation,7c,14g-j,18b,28 and olefin polymerization,19a,d,28c arguing for
a sterically demanding transition state in turnover-limiting olefin
insertion into Ln-X bonds (X ) H, P, C). Interestingly, and
in marked contrast to these olfein insertion reactions, the present
process involving alkyne insertion reactions clearly reveals a
modest deceleration rather than an acceleration in rates when
the larger lanthanide ions and more open Me2SiCp′′2Ln-
coordinate spheres are used as the catalysts (Tables 1 and 3). It
would appear that the steric demands in lanthanide-mediated
alkyne insertions are considerably relaxed. The results likely
reflect a combination of smaller substrate CtC steric bulk,
differences in number and/or orientation of substrate
coordination,7d and, in a Hammond-type picture,29 a more
reactant-like, sterically distinct transition state for such an
exothermic insertion process.
Conclusions
The evidence presented here shows that organolanthanide
centers are competent for the efficient, regioselective insertion
of alkynes into metal-amide bonds and that such processes can
be incorporated into efficient catalytic cycles for the hydroami-
nation/cyclization of a variety of aminoalkynes. The present
process provides an efficient method for the catalytic synthesis
of pyrrole, pyridine, and azepin derivatives. The catalytic
reaction scope includes primary amines, secondary amines,
terminal alkynes, and internal alkynes. The turnover frequencies
for this organolanthanide-catalyzed aminoalkyne cyclization are
found to be highly dependent on substrate substituents, on the
size of the lanthanide ion, and on the catalyst ancillary ligation.
Compared to the corresponding aminoolefin cyclizations, a
similar mechanism and rate law appear operative. Nevertheless,
substantially different metal, ancillary ligation, and substrate
substituent effects are observed in the present catalytic cycliza-
tions.
Acknowledgment. We thank NSF for generous support of
this research under Grant CHE9104112. We thank Dr. I. D. L.
Albert for the AM-1 calculations.
(28) (a) Fendrick, C. M.; Schertz, L. D.; Day, V. W.; Marks, T. J.
Organometallics 1988, 7, 1828-1838. (b) Conticello, V. P.; Brard, L.;
Giardello, M. A.; Tsuji, T.; Sabat, M.; Stern, C.; Marks, T. J. J. Am. Chem.
Soc. 1992, 114, 2761-2762. (c) Mauermann, H.; Marks, T. J. Organo-
metallics 1985, 4, 200-202. (d) Heeres, H. J.; Renkema, J.; Booji, M.;
Meetsma, A.; Teuben, J. H. Organometallics 1988, 7, 2495-2502.
JA9612413
(29) (a) Hammond, G. S. J. Am. Chem. Soc. 1955, 77, 334-338. (b)
Reference 26, Chapter 2.