Lanthanide- and actinide-mediated terminal alkyne hydrothiolation for the catalytic synthesis of markovnikov vinyl sulfides

Article abstract of DOI:10.1021/om100697h

The Markovnikov-selective lanthanide- and actinide-mediated, intermolecular hydrothiolation of terminal alkynes by aliphatic, benzylic and aromatic thiols using Cp*₂LnCH(TMS)₂ (Cp* = C ₅Me₅; Ln = La, Sm, Lu), Ln

Full text of DOI:10.1021/om100697h

6308 Organometallics 2010, 29, 6308–6320
DOI: 10.1021/om100697h
Lanthanide- and Actinide-Mediated Terminal Alkyne Hydrothiolation for
the Catalytic Synthesis of Markovnikov Vinyl Sulfides
Charles J. Weiss, Stephen D. Wobser, and Tobin J. Marks*
Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States
Received July 15, 2010
The Markovnikov-selective lanthanide- and actinide-mediated, intermolecular hydrothiolation of
terminal alkynes by aliphatic, benzylic and aromatic thiols using Cp*2LnCH(TMS)2 (Cp* = C5Me5;
Ln = La, Sm, Lu), Ln[N(TMS)2]3 (Ln = La, Nd, Y), Cp*2An(CH2TMS)2, and Me2SiCp00 An-
2
(CH2R)2 (Cp00 = C5Me4; An = Th, R = TMS; An = U, R = Ph) as precatalysts is studied in detail.
These transformations are shown to be Markovnikov-selective, with selectivities as high as >99%.
Kinetic investigations of the Cp*2SmCH(TMS)2-mediated reaction between 1-pentanethiol and
1-hexyne are found to be first-order in catalyst concentration, first-order in alkyne concentration,
and zero-order in thiol concentration. Deuterium labeling of the alkyne -CtC-H position reveals
kH/kD = 1.40(0.1) and 1.35(0.1) for the organo-Sm- and organo-Th-catalyzed processes, respec-
tively, along with evidence of thiol-mediated protonolytic detachment of the vinylic hydrothiolation
product from the Sm center. Mechanistic findings indicate turnover-limiting alkyne insertion into the
Sm-SR bond, followed by very rapid, thiol-induced M-C protonolysis to yield Markovnikov vinyl
sulfides and regenerate the corresponding M-SR species. Comparisons of different substrates and
metal complexes in catalyzing hydrothiolation reveal a strong dependence of hydrothiolation activity
on the steric encumbrance in the insertive transition state. Observed deuterium exchange between
alkyne -CtC-H and thiol RS-H in the presence of Cp*2SmCH(TMS)2 and Me2SiCp00 Th-
2
(CH2TMS)2 argues for a metal-alkynyl h metal-thiolate equilibrium, favoring the M-SR species
under hydrothiolation conditions. A mixture of free radical-derived anti-Markovnikov vinyl sulfides
is occasionally observed and can be suppressed by γ-terpinene radical inhibitor addition. Previously
reported metal thiolate complex aggregation to form insoluble species is observed and can be delayed
kinetically by Cp-based ligation.
Introduction
natural products,4 giving impetus to discovering more efficient
and selective methods to incorporate sulfur into organic
frameworks. The addition of S-H bonds across alkynes is
an atom-economical route to a variety of vinyl sulfides. While
radical reactions for the formation of S-C bonds have been
known to form unselective mixtures of E and Z vinyl sulfides
for decades (eq 1a),5 only in the past few years has the
application of transition metal and f-element catalysts to this
transformation (eqs 1b and c)6 received a surge of attention.
Among the
Sulfur-carbon bonds are a critical constituent of many
pharmaceuticals,1 materials,2 synthetic reagents,2b,c,f,3 and
*To whom correspondence should be addressed. E-mail: t-marks@
northwestern.edu.
(1) (a) Ma, Z.; Rao, L.; Bierbach, U. J. Med. Chem. 2009, 52, 3424–
ꢀ
ꢀ
ꢀ
ꢀ
3427. (b) Szilagyi, A.; Fenyvesi, F.; Majercsik, O.; Pelyvas, I. F.; Bacskay, I.;
ꢀ
ꢀ
ꢀ
Feher, P.; Varadi, J.; Vecsernyes, M.; Herczegh, P. J. Med. Chem. 2006, 49,
5626–5630. (c) Johannesson, P.; Lindeberg, G.; Johansson, A.; Nikiforovich,
G. V.; Gogoll, A.; Synnergren, B.; Le Greves, M.; Nyberg, F.; Karlen, A.;
Hallberg, A. J. Med. Chem. 2002, 45, 1767–1777. (d) Rocheblave, L.; Bihel,
F.; De Michelis, C.; Priem, G.; Courcambeck, J.; Bonnet, B.; Chermann,
J.-C.; Kraus, J.-L. J. Med. Chem. 2002, 45, 3321–3324.
(2) (a) Cortez, M. A.; Grayson, S. M. Macromolecules 2010, 43, 4081–
4090. (b) Konkolewicz, D.; Gray-Weale, A.; Perrier, S. B. J. Am. Chem. Soc.
2009, 131, 18075–18077. (c) Kloxin, C. J.; Scott, T. F.; Bowman, C. N.
Macromolecules 2009, 42, 2551–2556. (d) Ahmed, E.; Kim, F. S.; Xin, H.;
Jenekhe, S. A. Macromolecules 2009, 42, 8615–8618. (e) Fairbanks, B. D.;
Scott, T. F.; Kloxin, C. J.; Anseth, K. S.; Bowman, C. N. Macromolecules
2008, 42, 211–217. (f ) Valdebenito, A.; Encinas, M. V. Polymer 2005, 46,
10658–10662.
(3) (a) San Miguel, L.; Matzger, A. J. Macromolecules 2007, 40, 9233–
9237. (b) Roncali, J. Chem. Rev. 1992, 92, 711–738.
(4) (a) Meng, D.; Chen, W.; Zhao, W. J. Nat. Prod. 2007, 70, 824–829.
(b) Zhang, Y.; Liu, S.; Che, Y.; Liu, X. J. Nat. Prod. 2007, 70, 1522–1525.
(c) Nicolaou, K. C.; Sorensen, E. J. Classics in Total Synthesis; Wiley-VHC:
New York, 1996.
previously reported catalysts exhibiting alkyne hydrothiolation
activity are Rh,6f,g,i,r,u Ir,6d Ni,6c,k,l,n-p,s Pd,6c,k,m,uPt,6k Au,6b
Zr,6a Th,6e and U6e (e.g., eqs 2-4).6a,g,p While Au, Rh, and Ir
catalysts often favor Eanti-Markovnikov products (e.g., eq 4),7
Ni, Pd, Pt, and Zr catalysts favor the Markovnikov vinyl sulfides
r
pubs.acs.org/Organometallics
Published on Web 11/09/2010
2010 American Chemical Society

Article
Organometallics, Vol. 29, No. 23, 2010 6309
(e.g., eqs 2 and 3). This Markovnikov selectivity observed
with the latter catalysts is thought to result from a pathway
involving insertion of alkyne into a M-SR bond (see more
below).6a,l
anti-Markovnikov products can be suppressed by the addi-
tion of a radical inhibitor, implicating a known, nonmetal-
centered, radical-mediated side reaction.5b-f Among the
most notable attractions of these actinide catalysts is their
demonstrated ability to accommodate a wide range of thiols.
While many late transition metal complexes are competent
to mediate this transformation with arylthiols,6 few have
exhibited the same activity with the less reactive aliphatic
thiols.6g,h,m,r,9 Kinetic and mechanistic studies of these
organoactinide-mediated transformations led to the proposed
insertion/protonolysis sequence of Scheme 1, where the
Markovnikov insertion of alkyne into a Th-SR bond is
turnover-limiting, followed by a very rapid, thiol-mediated
protonolysis of the vinyl sulfide group from the metal to yield
vinyl sulfide product and regenerate the catalyst. Examina-
tion of organoactinide-mediated hydrothiolation activity as
a function of substrate shows that while both steric encum-
brance and the electronic structure of the thiols and alkynes
influence hydrothiolation activity, thiol steric characteristics
dominate. Furthermore, the selectivity of this transforma-
tion scales inversely with the ability of a given substrate to
initiate and propagate the aforementioned radical side
reaction.5b-f
We previously communicated that organothorium and
organouranium complexes8 are highly selective catalysts
for the synthesis of Markovnikov vinyl sulfides.6e Interest-
ingly, it was also shown that the occasional formation of
(5) (a) Lo Conte, M.; Pacifico, S.; Chambery, A.; Marra, A.; Dondoni, A.
J. Org. Chem. 2010, 75, 4644–4647. (b) Capella, L.; Montevecchi, P. C.;
Navacchia, M. L. J. Org. Chem. 1996, 61, 6783–6789. (c) Benati, L.;
Capella, L.; Montevecchi, P. C.; Spagnolo, P. J. Chem. Soc., Perkin
Trans. 1995, 1035–1038. (d) Benati, L.; Montevecchi, P. C.; Spagnolo,
P. J. Chem. Soc., Perkin Trans. 1991, 2103–2109. (e) Ichinose, Y.;
Wakamatsu, K.; Nozaki, K.; Birbaum, J.-L.; Oshima, K.; Utimoto, K.
Chem. Lett. 1987, 16, 1647–1650. (f ) Griesbaum, K. Angew. Chem.,
Int. Ed. Engl. 1970, 9, 273–287.
Lanthanide complexes8k,10 are highly active and selective
reagents for analogous alkyne hydroamination,8i,11 hydro-
phosphination,11e,12 and hydroalkoxylation11e,13 processes.
However, organolanthanide complexes also exhibit large
Ln-SR (Ln = lanthanide) bond enthalpies14 and are known
to form thiolate aggregates,10e,15 raising concern about
whether the insertion of carbon-carbon unsaturations into
this type of bond is even possible. In light of the recently
(6) (a) Weiss, C. J.; Marks, T. J. J. Am. Chem. Soc. 2010, 132, 10533–
ꢀ
ꢀ
10546. (b) Corma, A.; Gonzalez-Arellano, C.; Iglesias, M.; Sanchez, F. Appl.
Catal., A 2010, 375, 49–54. (c) Ananikov, V. P.; Gayduk, K. A.; Orlov, N. V.;
Beletskaya, I. P.; Khrustalev, V. N.; Antipin, M. Y. Chem. Eur. J. 2010, 16,
;
2063–2071. (d) Field, L. D.; Messerle, B. A.; Vuong, K. Q.; Turner, P. Dalton
Trans. 2009, 3599–3614. (e) Weiss, C. J.; Wobser, S. D.; Marks, T. J. J. Am.
Chem. Soc. 2009, 131, 2062–2063. (f ) Sabarre, A.; Love, J. Org. Lett. 2008,
10, 3941–3944. (g) Shoai, S.; Bichler, P.; Kang, B.; Buckley, H.; Love, J. A.
Organometallics 2007, 26, 5778–5781. (h) Kondoh, A.; Yorimitsu, H.;
Oshima, K. Org. Lett. 2007, 9, 1383–1385. (i) Fraser, L. R.; Bird, J.; Wu,
Q.; Cao, C.; Patrick, B. O.; Love, J. A. Organometallics 2007, 26, 5602–
5611. ( j) Delp, S. A.; Munro-Leighton, C.; Goj, L. A.; Ramirez, M. A.;
Gunnoe, T. B.; Petersen, J. L.; Boyle, P. D. Inorg. Chem. 2007, 46, 2365–
2367. (k) Beletskaya, I. P.; Ananikov, V. P. Pure Appl. Chem. 2007, 79,
1041–1056. (l) Beletskaya, I. P.; Ananikov, V. P. Eur. J. Org. Chem. 2007,
3431–3444. (m) Ananikov, V. P.; Orlov, N. V.; Beletskaya, I. P.; Khrustalev,
V. N.; Antipin, M. Y.; Timofeeva, T. V. J. Am. Chem. Soc. 2007, 129, 7252–
7253. (n) Malyshev, D. A.; Scott, N. M.; Marion, N.; Stevens, E. D.;
Ananikov, V. P.; Beletskaya, I. P.; Nolan, S. P. Organometallics 2006, 25,
4462–4470. (o) Ananikov, V. P.; Zalesskiy, S. S.; Orlov, N. V.; Beletskaya,
I. P. Russ. Chem. Bull. 2006, 55, 2109–2113. (p) Ananikov, V. P.; Orlov,
N. V.; Beletskaya, I. P. Organometallics 2006, 25, 1970–1977. (q) Misumi,
Y.; Seino, H.; Mizobe, Y. J. Organomet. Chem. 2006, 691, 3157–3164.
(r) Cao, C.; Fraser, L. R.; Love, J. A. J. Am. Chem. Soc. 2005, 127, 17614–
17615. (s) Ananikov, V. P.; Malyshev, D. A.; Beletskaya, I. P.; Aleksandrov,
G. G.; Eremenko, I. L. Adv. Synth. Catal. 2005, 347, 1993–2001. (t) Kondo,
T.; Mitsudo, T. Chem. Rev. 2000, 100, 3205–3220. (u) Ogawa, A.; Ikeda, T.;
Kimura, K.; Hirao, T. J. Am. Chem. Soc. 1999, 121, 5108–5114.
(v) Kuniyasu, H.; Ogawa, A.; Sato, K.; Ryu, I.; Kambe, N.; Sonoda, N.
J. Am. Chem. Soc. 1992, 114, 5902–5903.
(9) This diminished activity is attributed to the greater RS-H bond
enthalpy in alihpatic versus aromatic thiols. See ref 6m.
(10) (a) Seitz, M.; Oliver, A. G.; Raymond, K. N. J. Am. Chem. Soc.
2007, 129, 11153–11160. (b) Evans, W. J.; Davis, B. L. Chem. Rev. 2002,
102, 2119–2136. (c) Molander, G. A.; Romero, J. A. C. Chem. Rev. 2002,
102, 2161–2186. (d) Aspinall, H. C. Chemistry of the f-Block Elements;
Taylor & Francis: Washington, D.C., 2001. (e) Aspinall, H. C.; Cunningham,
S. A.; Maestro, P.; Macaudiere, P. Inorg. Chem. 1998, 37, 5396–5398.
(11) (a) Broderick, E. M.; Gutzwiller, N. P.; Diaconescu, P. L.
Organometallics 2010, 29, 3242-3251. (b) M€uller, T. E.; Hultzsch, K. C.;
Yus, M.; Foubelo, F.; Tada, M. Chem. Rev. 2008, 108, 3795–3892. (c)
ꢁ
Hartwig, J. F. Nature 2008, 455, 314–322. (d) Motta, A.; Fragala, I. L.;
Marks, T. J. Organometallics 2006, 25, 5533–5539. (e) Alonso, F.;
Beletskaya, I. P.; Yus, M. Chem. Rev. 2004, 104, 3079–3160. (f ) Motta,
A.; Lanza, G.; Fragala, I. L.; Marks, T. J. Organometallics 2004, 23, 4097–
4104. (g) Hong, S.; Marks, T. J. Acc. Chem. Res. 2004, 37, 673–686. (h)
Ackermann, L.; Bergman, R. G.; Loy, R. N. J. Am. Chem. Soc. 2003, 125,
11956–11963. (i) Hong, S.; Kawaoka, A. M.; Marks, T. J. J. Am. Chem. Soc.
2003, 125, 15878–15892. ( j) Hong, S.; Marks, T. J. J. Am. Chem. Soc. 2002,
124, 7886–7887. (k) Arredondo, V. M.; McDonald, F. E.; Marks, T. J.
Organometallics 1999, 18, 1949–1960. (l) Arredondo, V. M.; Tian, S.;
McDonald, F. E.; Marks, T. J. J. Am. Chem. Soc. 1999, 121, 3633–3639.
(m) Arredondo, V. M.; McDonald, F. E.; Marks, T. J. J. Am. Chem. Soc.
1998, 120, 4871–4872. (n) Haskel, A.; Straub, T.; Eisen, M. S. Organome-
tallics 1996, 15, 3773–3775. (o) Giardello, M. A.; Conticello, V. P.; Brard, L.;
Gagne, M. R.; Marks, T. J. J. Am. Chem. Soc. 1994, 116, 10241–10254. (p)
Li, Y.; Fu, P.-F.; Marks, T. J. Organometallics 1994, 13, 439. (q) Gagne,
M. R.; Stern, C. L.; Marks, T. J. J. Am. Chem. Soc. 1992, 114, 275–294.
(7) With the noteable exception of Tp*Rh(PPh3)2 (ref 6i).
(8) (a) Schreckenbach, G.; Shamov, G. A. Acc. Chem. Res. 2010, 43,
19–29. (b) Schelter, E. J.; Wu, R.; Veauthier, J. M.; Bauer, E. D.; Booth, C. H.;
Thomson, R. K.; Graves, C. R.; John, K. D.; Scott, B. L.; Thompson, J. D.;
Morris, D. E.; Kiplinger, J. L. Inorg. Chem. 2010, 49, 1995–2007.
(c) Thomson, R. K.; Graves, C. R.; Scott, B. L.; Kiplinger, J. L. Dalton
Trans. 2010, Earlyview. (d) Cantat, T.; Scott, B. L.; Morris, D. E.; Kiplinger,
J. L. Inorg. Chem. 2009, 48, 2114–2127. (e) Cantat, T.; Graves, C. R.;
Jantunen, K. C.; Burns, C. J.; Scott, B. L.; Schelter, E. J.; Morris, D. E.; Hay,
P. J.; Kiplinger, J. L. J. Am. Chem. Soc. 2008, 130, 17537–17551. (f ) Fox,
A. R.; Bart, S. C.; Meyer, K.; Cummins, C. C. Nature 2008, 455, 341–349.
(g) Andrea, T.; Barnea, E.; Eisen, M. S. J. Am. Chem. Soc. 2008, 130, 2454–
2455. (h) Wang, J.; Gurevich, Y.; Botoshansky, M.; Eisen, M. S. Organo-
metallics 2008, 27, 4494–4504. (i) Andrea, T.; Eisen, M. S. Chem. Soc. Rev.
2008, 37, 550–567. ( j) Wang, J.; Gurevich, Y.; Botoshansky, M.; Eisen, M. S.
J. Am. Chem. Soc. 2006, 128, 9350–9351. (k) Cotton, S. Lanthanide and
Actinide Chemistry; John Wiley & Sons, Ltd: Uppingham, Rutland, UK,
2006. (l) Dash, A. K.; Wang, J. Q.; Eisen, M. S. Organometallics 1999, 18,
4724–4741. (m) Marks, T. J. Science 1982, 217, 989–97.
(12) (a) Perrier, A.; Comte, V.; Moıse, C.; Le Gendre, P. Chem. Eur.
;
J. 2009, 16, 64–67. (b) Douglass, M. R.; Marks, T. J. J. Am. Chem. Soc.
2000, 122, 1824–1825. (c) Douglass, M. R.; Stern, C. L.; Marks, T. J. J. Am.
Chem. Soc. 2001, 123, 10221–10238. (d) Kawaoka, A. M.; Douglass, M. R.;
ꢁ
Marks, T. J. Organometallics 2003, 22, 4630–4632. (e) Motta, A.; Fragala,
I. L.; Marks, T. J. Organometallics 2005, 24, 4995–5003. (f ) Nagata, S.;
Kawaguchi, S.-i.; Matsumoto, M.; Kamiya, I.; Nomoto, A.; Sonoda, M.;
Ogawa, A. Tetrahedron Lett. 2007, 48, 6637–6640. (g) Sadow, A. D.;
Haller, I.; Fadini, L.; Togni, A. J. Am. Chem. Soc. 2004, 126, 14704–14705.
(h) Takaki, K.; Koshoji, G.; Komeyama, K.; Takeda, M.; Shishido, T.; Kitani,
A.; Takehira, K. J. Org. Chem. 2003, 68, 6554–6565. (i) Wicht, D. K.;
Kourkine, I. V.; Lew, B. M.; Nthenge, J. M.; Glueck, D. S. J. Am. Chem. Soc.
1997, 119, 5039–5040.

6310 Organometallics, Vol. 29, No. 23, 2010
Weiss et al.
Scheme 1. Proposed Catalytic Cycle for Organothorium-Mediated Alkyne Hydrothiolation6e
Table 1. Estimated ΔH’s (kcal/mol) for Proposed/Predicted
Organothorium- and Organosamarium-Mediated Insertion/
Protonolysis Hydrothiolation Cycles (see Scheme 1)18
communicated efficacy of organozirconium and organoac-
tinide complexes in effecting highly Markovnikov-selective
alkyne hydrothiolation,6a,e the intriguing question arises as
to whether and with what efficacy analogous organolantha-
nide complexes might effect alkyne hydrothiolation.
Bond enthalpy considerations for the unexplored,
lanthanide-mediated variant of Scheme 1 (Table 1)16 pre-
dict net exothermicity for thiol addition to alkynes and
alkenes mediated by organolanthanide complexes. However,
while alkyne insertion into a Sm-SR bond (step ii) is
predicted to be exothermic by ca. -12 kcal/mol, alkenes will
be more challenging, with insertions predicted to be endo-
thermic by ca. þ23 kcal/mol. The final protonolysis process
(step iii) is estimated to be highly exothermic for all substrates,
reflecting the substantial product C-H and Sm-SR bond
enthalpies. Importantly, the exothermicity of alkyne insertion
into a Sm-SR bond taken together with the kinetic lability of
metal/C-C unsaturation
step ii (insertion)
step iii (protonolysis)
Samarium
alkene
alkyne
þ23
-12
-43
-33
Thorium
alkene
alkyne
þ12
-19
-32
-26
lanthanide complexes suggests favorable conditions for
catalysis,13b while the endothermicity of the analogous alkene
insertion is expected to be more prohibitive.17 These predictions
parallel reported thermodynamic estimates for organoactinide
complexes.6a,e Herein we report a detailed study of organo-
lanthanide-mediated alkyne hydrothiolation with scope and
mechanistic considerations discussed. We compare and con-
trast these 4f results with our earlier 5f results.
ꢁ
(13) (a) Motta, A.; Fragala, I. L.; Marks, T. J. Organometallics 2010,
29, 2004–2012. (b) Weiss, C. J.; Marks, T. J. Dalton Trans. 2010, 39, 6576–
Experimental Section
6588, perspective. (c) Dzudza, A.; Marks, T. J. Chem. Eur. J. 2010, 16,
;
3403–3422. (d) Seo, S.; Marks, T. J. Chem. Eur. J. 2010, 16, 5148–5162.
;
(e) Cui, D.-M.; Yu, K.-R.; Zhang, C. Synlett 2009, 7, 1103–1106. (f ) Dzudza,
A.; Marks, T. J. Org. Lett. 2009, 11, 1523–1526. (g) Janini, T. E.; Rakosi,
R. I.; Durr, C. B.; Bertke, J. A.; Bunge, S. D. Dalton Trans. 2009, 10601–
10608. (h) Nishina, N.; Yamamoto, Y. Tetrahedron 2009, 65, 1799–1808.
(i) Seo, S.; Yu, X.; Marks, T. J. J. Am. Chem. Soc. 2009, 131, 263–276.
( j) Zhang, Z.; Widenhoefer, R. A. Org. Lett. 2008, 10, 2079–2081.
(k) Nishina, N.; Yamamoto, Y. Tetrahedron Lett. 2008, 49, 4908–4911.
(l) Harkat, H.; Weibel, J.-M.; Pale, P. Tetrahedron Lett. 2007, 48, 1439–
1442. (m) Yu, X.; Seo, S.; Marks, T. J. J. Am. Chem. Soc. 2007, 129, 7244–
7245. (n) Zhang, Z.; Liu, C.; Kinder, R. E.; Han, X.; Qian, H.; Widenhoefer,
R. A. J. Am. Chem. Soc. 2006, 128, 9066–9073. (o) Yang, C. G.; Reich,
N. W.; Shi, Z.; He, C. Org. Lett. 2005, 7, 4553–4556. (p) Qian, H.; Han, X.;
Widenhoefer, R. A. J. Am. Chem. Soc. 2004, 126, 9536–9537.
(14) (a) Marks, T. J. Bonding Energetics in Organometallic Com-
pounds; American Chemical Society: Washington, D.C., 1990. (b) Nolan,
S. P.; Stern, D.; Marks, T. J. J. Am. Chem. Soc. 1989, 111, 7844–7853.
(15) (a) Zhang, Z.; Zhang, L.; Li, Y.; Hong, L.; Chen, Z.; Zhou, X.
Inorg. Chem. 2010, 49, 5715–5722. (b) Zhang, Z.-X.; Li, Y.-R.; Liu, R.-T.;
Chen, Z.-X.; Weng, L.-H.; Zhou, X.-G. Polyhedron 2007, 4986–4992.
(c) Cheng, M.-L.; Li, H.-X.; Zhang, W.-H.; Ren, Z.-G.; Zhang, Y.; Lang,
J.-P. Eur. J. Org. Chem. 2007, 2007, 1889–1896. (d) Li, H. X.; Ren, Z. G.;
Zhang, Y.; Zhang, W. H.; Lang, J. P.; Shen, Q. J. Am. Chem. Soc. 2005, 127,
1122–1123. (e) Wu, Z.-Z.; Huang, Z.-E.; Cai, R.-F.; Zhou, X.-G.; Xu, Z.; You,
X.-Z.; Huang, X.-Y. J. Organomet. Chem. 1996, 506, 25–30.
Materials and Methods. Due to the air- and moisture-
sensitivity of the organolanthanide and organoactinide complexes
used in this study, all manipulations were carried out in oven-
dried, Schlenk-type glassware interfaced to a high-vacuum line
(10-6 Torr) or in a nitrogen-filled glovebox (<1 ppm O2). Argon
(Airgas) was further purified by passing through columns of
˚
MnO and activated 4 A Davison molecular sieves immediately
before use. Benzene for preparative-scale and THF-d8 and
benzene-d6 (Cambridge Isotope Laboratories, 99þ atom % D)
for NMR-scale reactions and kinetic measurements were stored
over Na/K alloy in vacuo and vacuum transferred immediately
prior to use or were stored in a nitrogen-filled glovebox until use.
Pyridine-d5 was stored over CaH2 and vacuum transferred prior to
use. Thiols and alkynes were purchased from Aldrich, VWR,
GFS Chemicals, and Acros; they were distilled and transferred
˚
across multiple beds of activated Davison 4 A molecular sieves as
solutions in benzene-d6 or neat, followed by degassing (10-6 Torr)
via freeze-pump-thaw methods. Phenylacetylene-d (26-d) was
(17) Attempts to insert unactivated olefins into Ln-SR and An-SR
bonds have thus far been unsuccessful.
(16) See Supporting Information for bond enthalpy calculations.

Article
Organometallics, Vol. 29, No. 23, 2010 6311
Figure 1. 1H NMR (500 MHz) spectrum of the reaction 6 þ 14 f 15 mediated by a Cp*2SmCH(TMS)2 (5) precatalyst in benzene-d6
with 3ꢀ molar excess of 1-hexyne (A), the completed reaction after 16.0 h in a 120 °C oil bath with 5 mol % catalyst (B), and the isolated
product (C).
prepared by literature methods.6a All substrates were stored under
argon in Teflon-valved glass storage tubes, and conjugated alkynes
and thiols were stored at -10 °C until use. The D2O was purchased
from Cambridge Isotope Laboratories (99.9 atom % D) and used
as received. The organolanthanide and organoactinide complexes
Ln[N(TMS)2]3 (Ln = La (1), Nd (2), and Y (3)),19 Cp*2LnCH-
(TMS)2 (Ln = La (4), Sm (5), Lu (6)),20 Cp*2An(CH2TMS)2
(An = Th (35), U (34)),21 and Me2SiCp002AnL2 (An = Th, L =
CH2TMS (32);22 An = U, L = CH2Ph (36)23) were prepared as
reported in the literature and stored in a nitrogen-filled glovebox
until use. Complexes 4, 5, 6, 32, 34, 35, and 36 were stored below
0 °C. The methyltriphenylsilane 1H NMR internal integration
standard was purchased from Strem, sublimed twice under high
vacuum, and stored in a glovebox. Product NMR spectroscopic
data agree with the published literature spectra (see Supporting
Information).6a,e,r,24
Kinetic Experiments. The same procedure as described above
was followed except that the sample was periodically removed
from the oil bath to collect 1H NMR spectra at room tempera-
ture. Turnover-frequency (Nt) was determined by the method of
initial rate,25 where a linear regression (R2 g 0.98) of data points
was taken early in the reaction before the substrates had been
appreciably consumed (see Supporting Information). Turnover
frequency (Nt) was determined by plotting [product] versus time
according to eq 5 and using slope to calculate Nt according to
eq 6, where [catalyst]0 = initial concentration of precatalyst and
t = time in h. All kinetic experiments in this study were
performed at 0.2 M [thiol] and [alkyne] unless otherwise indi-
cated. Samarium kinetics were performed at 2-3 mol % catalyst
loading unless otherwise indicated.
½productꢁ ¼ mt
ð5Þ
Physical and Analytical Measurements. NMR spectra were
recorded on Mercury 400 (400 MHz, 1H; 100 MHz, 13C; 61
m
Ntðh- 1Þ ¼
ð6Þ
2
1
MHz, H) and Avance III 500 (500 MHz, H; 125 MHz, 13C)
NMR spectrometers. Chemical shifts (δ) are referenced relative
to internal solvent or integration standard resonances and
reported relative to Me4Si. Spectra of air-sensitive reactions
and materials were taken in airtight, Teflon-valved J. Young
NMR tubes. Samples were heated in silicon oil baths with the
temperature controlled by an Ika ETS-D4 probe. GC data for
selectivity measurements were collected on a HP6890 GC-MS
equipped with a HP5972 detector and an HP-5MS (5% phe-
nylmethylsiloxane, 30 m ꢀ 250 μm ꢀ 0.25 μm) capillary column.
Typical NMR-Scale Catalytic Reaction. In a glovebox, Cp*2-
SmCH(TMS)2 (2, 3.0 mg, 5.2 μmol) and methyltriphenylsilane
(8.0 mg, 29.5 μmol) were dissolved in 0.6 mL of benzene-d6
and added to a J. Young NMR tube. The tube was sealed and
interfaced to a high-vacuum line, where 0.2 mL of thiol and
0.2 mL alkyne solutions (both 1.0 M in benzene-d6; 0.2 mmol; 38
molar excess) were syringed in simultaneously under an argon
flush. The reaction mixture was then sealed under argon and
placed in a preheated, temperature-controlled oil bath covered
with aluminum foil to shield reactions from ambient light.
½catalystꢁ0
Conversion and Selectivity Measurements. In the glovebox,
Cp*2SmCH(TMS)2 (2, 5.0 mg, 10 μmol) was dissolved in 0.4 mL
of benzene-d6 and the resulting solution transferred to a J.
Young NMR tube. The tube was then sealed and attached to
a high-vacuum line, where 0.2 mL of thiol and 0.6 mL of alkyne
solutions (both 1.0 M in benzene-d6; 0.2 mmol; 20 molar excess
in thiol) were syringed in under an argon flush. The reac-
tion mixture was then sealed, shaken well, and placed in a
temperature-controlled, 120 °C oil bath for 16.0 h. The product
selectivity was determined by GC/MS, while conversion was
determined by 1H NMR integrations against internal standards
or quantitatively liberated catalyst ligands. To purify products,
the reaction mixture was eluted through a silica gel plug with
∼10 mL of hexanes or decanted off precipitated catalyst to
remove metal. The filtrate was then pumped under vacuum
(10-3 mTorr) to remove the volatiles and yield pure product.
Larger Scale Procedure. In the glovebox, Cp*2SmCH(TMS)2
(5, 75 mg, 0.13 mmol) was added to an oven-dried, 20 mL
Teflon-valved, glass storage tube dissolved in 1 mL of benzene.
On a high-vacuum line, an additional 9 mL of benzene was
added by vacuum transfer. The tube was cooled to -78 °C, and
1-hexyne (7, 0.90 mL, 7.8 mmol) and benzylmercaptan (14, 0.30mL,
2.6 mmol) were syringed into the tube under an argon flush.
The vessel was sealed, thawed, and placed in a preheated 120 °C
oil bath for 36.0 h with no stirring.26 Under ambient conditions,
the catalyst was removed by filtering through silica gel, eluting
(18) See Supporting Information for bond enthalpy calculations.
(19) (a) Dash, A. K.; Razavi, A.; Mortreux, A.; Lehmann, C. W.;
Carpentier, J.-F. Organometallics 2002, 21, 3238–3249. (b) Schuetz, S. A.;
Day, V. W.; Sommer, R. D.; Rheingold, A. L.; Belot, J. A. Inorg. Chem. 2001,
40, 5292–5295.
(20) Jeske, G.; Lauke, H.; Mauermann, H.; Schumann, H.; Marks,
T. J. J. Am. Chem. Soc. 1985, 107, 8111–8118.
(21) Fagan, P. J.; Manriquez, J. M.; Maatta, E. A.; Seyam, A. M.;
Marks, T. J. J. Am. Chem. Soc. 1981, 103, 6650–6667.
(22) Stubbert, B. D.; Stern, C. L.; Marks, T. J. Organometallics 2003,
22, 4836–4838.
(23) Schnabel, R. C.; Scott, B. L.; Smith, W. H.; Burns, C. J.
J. Organomet. Chem. 1999, 14–23.
(25) (a) Ansyln, E. V.; Dougherty, D. A. Modern Physical Organic
Chemistry; University Science Books: Sausalito, CA, 2006. (b) Espenson,
J. H. Chemical Kinetics and Reaction Mechanisms, 2nd ed.; McGraw-Hill:
New York, 1995. (c) Pilling, M. J.; Seakins, P. W. Reaction Kinetics; Oxford
University Press: New York, 1995.
(24) (a) Silveira, C. C.; Santos, P. C. S.; Mendes, S. R.; Braga, A. L.
J. Organomet. Chem. 2008, 3787–3790. (b) Fiandanese, V.; Marchese, G.;
Naso, F.; Ronzini, L. Synthesis 1987, 1034–1036.
(26) Similar attempts with stirring show drastically reduced conver-
sion, possibly the result of accelerated catalyst aggregation.

6312 Organometallics, Vol. 29, No. 23, 2010
Weiss et al.
Table 2. Effects of Organolanthanide Ionic Radius on Catalyst
Stability and Hydrothiolation Activity for the Hydrothiolation of
1-Hexyne by 1-Pentanethiol
precatalyst
complex
ionic
˚
radius (A)
precipitation
delay (h)a
32b
entry
Nt (h-1
)
b
1
2
3
Cp*2LaCH(TMS)2 (4)
Cp*2SmCH(TMS)2 (5)
Cp*2LuCH(TMS)2 (6)
1.160
1.079
0.977
0.1
0.5-6
>30
-
0.6
0.03
a Time in a sealed tube at 120 °C in benzene-d6 until precipitate is
observed. b Unable to measure Nt due to rapid precipitate formation.
with 20 mL of hexanes. The volatiles were then removed under
vacuum (10-3 mTorr) to yield 97% Markovnikov-pure 15 as a
yellow oil (0.22 g, 1.1 mmol, 41% yield). In addition to vinyl
sulfide products, 4 mol % alkyne dimer27 (2-butyloct-1-en-3-
yne)28 is observed.
Figure 2. Conversion (%) as a function of time in the hydro-
thiolation of 1-hexyne by 1-pentanethiol and 5 mol % Cp*2-
SmCH(TMS)2 (5) with 17ꢀ molar excess alkyne over thiol.
Conversion is based on thiol, and the lines are a guide to the eye.
Results
The principal goal of this study is to examine the scope and
selectivity of lanthanide- and actinide-mediated alkyne hy-
drothiolation and to define the sequence of steps by which
these transformations occur. We first report on lanthanide-
mediated hydrothiolation processes (e.g., Figure 1) with
information on catalyst stability along with substrate scope
and selectivity. This is followed by kinetic and mechanistic
experiments to elucidate the hydrothiolation pathway and
the source of the observed selectivity. Additional actinide
results are then presented to gain further insight beyond the
previously communicated data.6e We conclude with mecha-
nistic discussions: we first compare and contrast lanthanide
and actinide catalytic phenomenology and then discuss in
what ways these relate to analogous, organozirconium-
mediated alkyne hydrothiolation.6a
Catalyst Structure and Stability. Upon addition of 20-fold
excess RSH (R = pentyl, phenyl, or tert-butyl) to Ln[N-
(TMS)2]3 complexes (Ln = La (1), Nd (2), Y (3)) in benzene-d6,
a precipitate is immediately observed,29 similar to those
reported in the literature8k,10d,10e,15d as resulting from insoluble,
oligomeric lanthanide-thiolate complexes.10e,15b-15e,30 Despite
Ln[N(TMS)2]3 precipitation with excess thiol, trace hydrothio-
lation activity is nevertheless observed.31 Literature reports
indicate that using sterically hindered thiols10e,15c avoids pre-
cipitation at lower temperatures; however, we find that bulky
thiols delay but do not eliminate precipitate formation under
typical hydrothiolation conditions. In an attempt to avoid cata-
lyst precipitation, coordinating solvents10e,15d such as THF-d8
and pyridine-d5 were also examined; however precipitation
and/or low hydrothiolation activity was observed.
present lanthanide study because of their partial resistance to
precipitation in excess thiol at high temperatures. Interestingly,
catalyst stability scales inversely with lanthanide ionic radius,10a,32
with 4 forming a precipitate after heating at 120 °C for
0.1 h, 5 forming an observable precipitate only after 0.5-6 h at
120 °C, and 6 affording only minor precipitation after >30 h at
120 °C (Table 2). Note that while the Lu species are noticeably
more stable than those of Sm and La, they are found to be 20ꢀ
less active than Sm in catalyzing hydrothiolation under the same
reaction conditions.33 Therefore, complex 5 was chosen for
the present lanthanide study, offering a balance between
catalytic activity and reasonable stability under hydrothio-
lation conditions.
The addition of >20-fold excess 1-pentanethiol and
1-hexyne to Cp*2SmCH(TMS)2 (5) in benzene-d6 results in
quantitative formation of H2C(TMS)2,34 and approximately
40-60% of the Cp* ligands are rapidly cleaved protonoly-
tically from the metal center at room temperature, on the
1
basis of integration of the free Cp*H signals by H NMR
spectroscopy. Upon heating in a 120 °C bath, further ligand
protonolysis is gradually observed, often culminating in
observable precipitate formation after the majority of the
Cp* ligands have been detached. Examination of the cata-
lytic reaction progress at 120 °C reveals interesting trends
(Figure 2). During the first 0-6 min of reaction, an initial
surge in turnover is observed, followed by a stable period of
reduced activity. After approximately 0.5 h, a slight increase
in activity occurs, typically followed by observable catalyst
precipitation. Upon precipitate formation, the hydrothiola-
tion activity falls dramatically. Interestingly, examination of
analogous hydrothiolation with Cp*2LuCH(TMS)2 (6) re-
veals the same rapid cleavage of half the Cp* ligands from the
metal, but in contrast to Cp*2SmCH(TMS)2 (5), the second
ring protonolysis requires >30 h.35 The selection and
concentration of alkyne used under hydrothiolation condi-
tions also have a significant effect on catalyst stability.
In examining a range of alkynes having different steric
Sterically encumbered Cp*2LnCH(TMS)2 (Cp* = Me5C5,
Ln = La (4), Sm (5), Lu (6)) complexes were chosen for the
(27) Alkyne dimers are not observed in NMR-scale reactions. The
presence of the small quantities of dimer early in the preparative scale
likely results from 5-mediated dimerization of 1-hexyne before the
benzylmercaptan thaws.
(28) Komeyama, K.; Sasayama, D.; Kawabata, T.; Takehira, K.;
Takaki, K. J. Org. Chem. 2005, 70, 10679–10687.
(29) Precipitate colors vary as a function of lanthanide. See Support-
ing Information.
(32) (a) Evans, W. J. Inorg. Chem. 2007, 46, 3435–3449. (b) Shannon,
R. D. Acta Crystallogr. 1976, A32, 751–767.
(30) (a) Zhang, L.-X.; Zhou, X.-G.; Huang, Z.-E.; Cai, R.-F.; Huang,
X.-Y. Polyhedron 1999, 18, 1533–1537. (b) Mashima, K.; Nakayama, Y.;
Shibahara, T.; Fukumoto, H.; Nakamura, A. Inorg. Chem. 1996, 35, 93–99.
(31) It is unclear if this Markovnikov hydrothiolation activity is the
result of the heterogeneous species exhibiting hydrothiolation activity or
if it results from traces of homogeneous catalyst still remaining in
solution.
(33) The turnover frequency for complex 1 was unobtainable due to
heavy precipitate formation immediately after addition of excess thiol.
(34) The bis(trimethylsilyl)methane 1H resonances appear at δ 0.05
and -0.37 ppm in benzene-d6.
(35) No NMR data on ring cleavage rates for complex 4 were
obtainable due to large quantities of precipitation in the NMR tube.

Article
Organometallics, Vol. 29, No. 23, 2010 6313
Table 3. Cp*2SmCH(TMS)2 (5)-Mediated Intermolecular Hydrothiolation of 1-Hexyne (7)
a Markovnikov selectivity determined by 1H NMR and GC/MS after 16.0 h at 120 °C with 5 mol % Cp*2SmCH(TMS)2 (5) and a 3ꢀ molar excess of
alkyne. b Conversions of Markovnikov product determined by 1H NMR with respect to an internal integration standard and are reported with respect to
thiol.
Table 4. Catalytic Cp*2SmCH(TMS)2 (5)-Mediated Intermolecular Alkyne Hydrothiolation by 1-Pentanethiol (10)
as a Function of Alkyne
a Markovnikov selectivity determined by 1H NMR and GC/MS after 16.0 h at 120 °C with 5 mol % Cp*2SmCH(TMS)2 (5) and a 3ꢀ molar excess of
alkyne. b Conversion of Markovnikov product determined by 1H NMR with respect to an internal integration standard and reported with respect to
thiol. c Performed with γ-terpinene as a radical inhibitor in a 1:1 molar ratio to alkyne.
characteristics (see below), precipitation was observed more
rapidly with R-monosubstituted alkynes and phenylacety-
lene than with other R-disubstituted alkynes.36 Additionally,
large excesses of alkyne are found to delay precipitate
formation.
Selectivity and Conversion. To examine substrate scope, a
diverse selection of thiols and alkynes with a range of electronic
and steric characteristics was examined for conversion and
Markovnikov selectivity.37 Large effects are observed on
varying both the steric and electronic characteristics of the
thiol. In switching from ethanethiol to 1-pentanethiol
(Table 3, entry 1 vs 2), an almost 2ꢀ decrease in conversion
is observed, while cyclohexylmercaptan (Table 3, entry 3) suffers
an even more dramatic fall in conversion. Interestingly, both
benzylmercaptan and thiophenol (Table 3, entries 4 and 5) exhibit
moderate to high conversions, despite the significant steric
encumbrances. In spite of the large variations in conversion,
good to excellent selectivities are observed for all thiols
examined with 1-hexyne. While all aforementioned hydrothio-
lation reactions are >90% Markovnikov selective, somewhat
lower selectivities are observed with cyclohexylmercaptan and
thiophenol.
(36) Images of the resulting precipitates are provided in the Support-
ing Information.
(37) Unfortunately, due to rapid catalyst precipitation, turnover
frequencies could not be accurately measured for most thiols and
alkynes, preventing quantitative comparison of substrate hydrothiola-
tion activity.
On varying the alkyne electronic and steric characteristics,
dramatic differences in both hydrothiolation selectivity

6314 Organometallics, Vol. 29, No. 23, 2010
Weiss et al.
Table 5. Catalytic Cp*2SmCH(TMS)2 (5)-Mediated Intermolecular Alkyne Hydrothiolation by Benzylmercaptan (15)
a Markovnikov selectivity determined by 1H NMR and GC/MS after 16.0 h at 120 °Cwith5mol%Cp*2SmCH(TMS)2 (5) anda 3ꢀ molar excess of alkyne.
b Conversion of Markovnikov product determined by 1H NMR with respect to an internal integration standard and reported with respect to thiol.
Figure 3. Plot of product formation rate for the reaction 7 þ 10 f 11 as a function of [Cp*2SmCH(TMS)2 (5)] (A) and [1-hexyne (7)] (B)
with [1-pentanethiol (10)] and [1-hexyne (7)] = 0.2 M unless otherwise indicated. Plot of hydrothiolation conversion (%) versus time
with 17ꢀ molar excess 1-hexyne (7) over 1-penthanethiol (10) exhibits a linear trend (C),42 indicating a pseudo-zero-order reaction,
demonstrating rate independence with respect to [1-penthanethiol (10)] except at the highest concentrations, where catalyst
precipitation becomes extensive. The lines in plots in panels A, B, and C are least-squares fits.
and conversion are observed. While cyclohexylacetylene
(Table 4, entry 1) still affords high selectivity, it yields ca.
half the conversion observed for less encumbered 1-hexyne
(Table 3, entry 2). Moving the steric bulk from the R- to the
β-position gives comparable conversion and only moder-
ately improved selectivity. Introducing aromaticity R and
β to the alkyne fragment results in slight to moderately
increased conversion efficiency but dramatically depresses
the Markovnikov selectivity. The hydrothiolation activity
and selectivity of 1-ethynylcylclohexene and phenylacetylene
are both rather low. Interestingly, while 3-ethynylpyridine
exhibits over 2ꢀ the selectivity of phenylacetylene (Table 4,
entry 5 vs 6), the conversion is still low.38
Adding γ-terpinene as a radical inhibitor6a,e,l-n in a 1:1
molar ratio with alkyne effects large decreases in the yields of
anti-Markovnikov products for both 1-ethynylcyclohexene
and phenylacetylene (Table 5, entries 4 and 5). While this
radical inhibitor results in high Markovnikov selectivity for
phenylacetylene hydrothiolation, only moderate selectivity
is observed in the hydrothiolation of 1-ethynylcyclohexene.
Additional catalytic experiments with benzylmercaptan
(38) Additional internal alkyne and terminal R-trisubstituted alkynes
were surveyed and displayed little or no activity.

Article
Organometallics, Vol. 29, No. 23, 2010 6315
Figure 4. The 2 mol % Cp*2SmCH(TMS)2 (5)-mediated hydrothiolation of phenylacetylene-d (26-d) with 1-penthanethiol (10) gives a
mixture of Markovnikov product isotopomers. After 0.2 h at 120 °C in benzene-d6, primarily 27-dE is observed. Additional heating for
0.4 h (B), 0.75 h (C), and 2.0 h (D) reveals increasing ratios of 27 and 27-dZ products to 27-dE. Signal intensities are normalized to an
internal integration standard.
(Table 5) reveal increased yields and selectivities versus
1-penthanethiol (Table 3), despite the lower pKa of benzyl-
mercaptan.6m,39 Regrettably, selectivity and conversion are not
as high as those observed in the hydrothiolation of 1-hexyne by
benzylmercaptan (Table 3, entry 4).
Finally, the dependence of Nt on [1-penthanethiol] from
0.01 to 0.2 M at fixed 1-hexyne concentration (i.e., 3.5 M) to
force the reaction to pseudo-zero-order6e,41 shows the reaction
to be zero-order with respect to [thiol] (Figure 3C). The fall in
rate near the end of the reaction corresponds to the onset of
observable catalyst precipitation (Figure 3C). Therefore, the
empirical rate law, under standard catalytic conditions with
minimal catalyst precipitation, is given by eq 7.
Kinetics of Organosamarium- and Organothorium-Mediated
Intermolecular Alkyne Hydrothiolation. To develop a better
understanding of the reaction pathway, kinetic experiments
were performed to understand the effect catalyst and reactant
concentrations have on hydrothiolation turnover. Experiments
were conducted on the Cp*2SmCH(TMS)2 (5)-mediated
hydrothiolation of 1-hexyne (7) by 1-penthanethiol (10) in
benzene-d6 at 120 °C. The empirical rate law is derived by
examining the turnover frequency (Nt) while systematically
varying [catalyst], [alkyne], and [thiol]. By examining [Cp*2-
SmCH(TMS)2] from 0.4 to 8.6 mM, a linear trend is observed
for concentrations in the 0.4-5.2 mM range (Figure 3A),
indicating a first-order dependence on [catalyst] at lower
concentrations,40 while a fall in activity is observed at higher
concentrations. Attempts to explore the reaction at even higher
[Cp*2SmCH(TMS)2] values, 9-17 mM, resulted in reduced
activity and rapid catalyst precipitation from solution. An
investigation of the effects of increasing [1-hexyne] from 0.1
to 3.5 M reveals a linear correlation with activity over the
[1-hexyne (7)] range, 0.1-0.9 M (Figure 3B), indicating initial
first-order dependence on [alkyne]. On increasing the alkyne
concentration further, a slight reduction in activity is observed,
which may be the result of partial alkyne saturation of the metal
center and/or alkyne acting as a hydrothiolation inhibitor.
1
1
0
rate ¼ kobs½Smꢁ ½alkyneꢁ ½thiolꢁ
ð7Þ
To trace the fate of the PhCC-D (26-d) hydrogens during
Cp*2SmCH(TMS)2 (5)- and Me2SiCp00Th(CH2TMS)2 (32)-
mediated hydrothiolation, deuterium-labeling studies were
performed using deuterated phenylacetylene (26-d) and
1-penthanethiol (10). Exclusive observation of H2C(TMS)2
in the 1H and 2H NMR evidence thiol-mediated protonolytic
activation of the catalyst.43 By comparing the activity with
that of nondeuterated phenylacetylene, apparent KIEs of
kH/kD = 1.40(0.1) and 1.35(0.1) are observed for catalysts 5
and 32, respectively. At early reaction times, a single product
isotopomer is primarily observed (Figure 4A). However,
upon further heating, other known isotopomeric products
are observed (Figure 4B-D), along with substantial loss of
the phenylacetylene deuterium label. On the basis of 1H and
2H NMR spectroscopy, deuterium is observed to scramble
from the alkyne terminus to the thiol functionality, as
evidenced by a prominent RSD resonance in the 2H NMR.
To determine if the migration is the result of the catalytic
cycle, tert-butylmercaptan (33), phenylacetylene-d (26-d),
and either complex 5 or 32 were heated in benzene-d6 at
(39) (a) Bordwell, F. G.; Zhang, X.-M.; Satish, A. V.; Cheng, J. P. J.
Am. Chem. Soc. 1994, 116, 6605–6610. (b) Bordwell, F. G. Acc. Chem.
Res. 1988, 21, 456–463. (c) Janousek, B. K.; Reed, K. J.; Brauman, J. I. J.
Am. Chem. Soc. 1980, 102, 3125–3129. (d) Danehy, J. P.; Noel, C. J. J. Am.
Chem. Soc. 1960, 82, 2511–2515. (e) Kreevoy, M. M.; Harper, E. T.; Duvall,
R. E.; Wilgus, H. S.; Ditsch, L. T. J. Am. Chem. Soc. 1960, 82, 4899–4902.
(40) A plot of ln(rate) vs ln([catalyst]) does not give a linear trend,
furthur demonstrating that the hydrothiolation reaction is not second-
order with respect to [catalyst].
(41) Espenson, J. H. Chemical Kinetics and Reaction Mechanisms, 2nd
ed.; McGraw-Hill, Inc.: New York, 1995.
(42) Large excesses of alkyne are found to delay precipitate forma-
tion.
(43) Because no DHC(TMS)2 is observed, it can be estimated that
thiol-mediated protonolysis is >50ꢀ faster than analogous alkyne-
mediated protonolysis.

6316 Organometallics, Vol. 29, No. 23, 2010
Weiss et al.
Figure 5. Hydrothiolation of 1-hexyne (7) with 1-pentanethiol
(10) catalyzed by 6 mol % Cp*2U(CH2TMS)2 (34) in benzene-d6
at 120 °C.
Figure 6. Steric openness46,47 effects on Cp*2U(CH2TMS)2
(34)-, Cp*2Th(CH2TMS)2 (35)-, Me2SiCp002U(Bn)2 (Bn = ben-
zyl, 36)-, and Me2SiCp002Th(CH2TMS)2 (32)-mediated hydro-
thiolation of 1-hexyne (7) by 1-pentanethiol (10) in benzene-d6 at
120 °C.48
120 °C for 0.75 h. Proton NMR integration indicates that
15-30% of the deuterium migrates from the alkyne during
this time period despite the fact that no measurable hydro-
thiolation product is observed.44 A control experiment with-
out the addition of catalyst results in no detectable deuterium
scrambling.6a
conversion, but the addition of a radical inhibitor substan-
tially increases both selectivity and conversion.
Organoactinide-Mediated Alkyne Hydrothiolation. The ef-
ficacy of Me2SiCp002Th(CH2TMS)2 (32) in alkyne hydro-
thiolation raises the question of how other Cp-based
actinide complexes might perform. In investigating Cp*2U-
(CH2TMS)2 (34)-mediated hydrothiolation, an interesting
pattern is observed (Figure 5). During the initial 2 h of
turnover, product is formed at a constant rate. After another
approximately 2 h, a gradual increase in activity is observed,
correlating with the observation of free Cp*H by 1H NMR.
After approximately 15 h of reaction, the activity falls
dramatically as an observable precipitate is formed. Similar
trends are observed with organoactinide complexes 32, 35,
and 36.45
In examining the importance of organoactinide complex
ionic radius32b and ligation geometry on hydrothiolation
activity,46 significant effects of steric constraints around the
metal center on hydrothiolation activity are observed. Changing
the ancillary ligation from Cp*2 to Me2SiCp002 and the metal ion
size from U(IV) to Th(IV) results in a substantial opening of the
coordination sphere.46,47 As steric encumbrance is decreased,
hydrothiolation turnover frequency increases (Figure 6). To
examine the efficacy of Cp*2Th(CH2TMS)2 (35)-mediated
hydrothiolation, selectivity and conversion were examined for
several thiol þ alkyne combinations. While the hydrothiolation
of cyclohexylacetylene by 1-pentanethiol (Table 6, entry 1)
results in good selectivity, the conversion is relatively low.
Similarly, good selectivity is observed in the hydrothiolation
of 1-hexyne by benzylmercaptan (Table 6, entry 2), but low
conversion is again achieved. Finally, phenylacetylene and
thiophenol (Table 6, entry 3) afford both low selectivity and
Discussion
Ancillary Ligand and Metal Effects on Catalyst Stability.
Ancillary ligand selection has major consequences for the
stability of organolanthanide and organoactinide6e com-
plexes in hydrothiolation catalysis. While the addition of
excess thiol to Ln[N(TMS)2]3 precatalysts results in immediate
precipitation,10e cyclopentadienyl (Cp)-based ligation delays
precipitation. This is similar to observations in analogous
organozirconium-mediated alkyne hydrothiolation6a where
Zr[NMe2]4 undergoes precipitation soon after addition of excess
thiol, whereas no precipitate is observed with organozirconium
Cp* and CGC (CGC = Me2SiCp00NCMe3, Cp00 = C5Me4)
complexes. The nonbonded repulsions of the Cp-based ligands
likely suppress the formation of insoluble, highly aggregated
species.6e Likewise, the Cp* and Me2SiCp00 ligands must
2
similarly delay the formation of previously reported, insoluble
lanthanide10e,15b-15e and actinide49 thiolate aggregates. Never-
theless, at higher Cp*2SmCH(TMS)2 concentrations, precipi-
tate formation occurs more rapidly, consistent with a catalyst
aggregation model.
In contrast to the behavior of the zirconium Cp*, Cp*2, and
CGC complexes,50 addition of excess thiol (typically 20-40ꢀ
excess) to the present organolanthanide and organoactinide
complexes results in immediate to gradual catalyst precipitation.
Due to the highly polar nature of f-element-ligand bonding,51
(48) Rate measured as beginning of reaction before signifigant ligand
protonolysis.
(49) Roger, M.; Barros, N.; Arliguie, T.; Thuery, P.; Maron, L.;
ꢀ
Ephritikhine, M. J. Am. Chem. Soc. 2006, 128, 8790–8802.
(50) Cp-based zirconium complexes are not observed to form insolu-
able aggregates except at extremely high thiol concentrations, exceeding
1 M, and after extended heating. Despite the observed aggregation, no
ligand cleavage is observed.
(51) (a) Krogh-Jespersen, K.; Romanelli, M. D.; Melman, J. H.;
Emge, T. J.; Brennan, J. G. Inorg. Chem. 2009, 49, 552–560. (b) Ingram,
K. I. M.; Tassell, M. J.; Gaunt, A. J.; Kaltsoyannis, N. Inorg. Chem. 2008, 47,
7824–7833. (c) Liu, G. K.; Jensen, M. P.; Almond, P. M. J. Phys. Chem. A
2006, 110, 2081–2088. (d) Guillaumont, D. J. Phys. Chem. 2004, 108,
6893–6900. (e) Strittmatter, R. J.; Bursten, B. E. J. Am. Chem. Soc. 1991,
113, 552–559. (f ) Nugent, L. J.; Laubereau, P. G.; Werner, G. K.;
Vander Sluis, K. L. J. Organomet. Chem. 1971, 27, 365–372.
(44) The 2H NMR spectrum after further heating shows that the
deuterium is migrating to the tBuSH resonance (1.6 ppm).
(45) Cp ring cleavage for both Cp*2An< and Me2SiCp002An<
complexes is observed occurring at approximately the same rate. Mean-
while, a comparison of Cp* ring cleavage from complexes 34 and 35
evidences ring cleavage from U at approximately 1/4 the rate observed
for Th.
(46) Stubbert, B. D.; Marks, T. J. J. Am. Chem. Soc. 2007, 129, 4253–
4271.
(47) Stubbert, B. D.; Marks, T. J. J. Am. Chem. Soc. 2007, 129, 6149–
6167.

Article
Organometallics, Vol. 29, No. 23, 2010 6317
Table 6. Cp*2Th(CH2TMS)2-Mediated Intermolecular Alkyne Hydrothiolation of 1-Hexyne by 1-Pentanethiol
a Markovnikov selectivity determined by 1H NMR and GC/MS after 16.0 h in benzene-d6 at 120 °C with 5 mol % Cp*2Th(CH2TMS)2 and a 3ꢀ molar
excess of alkyne. b Conversion of Markovnikov product determined by 1H NMR with respect to an internal integration standard and reported with
respect to thiol. c Performed with γ-terpinene as a radical inhibitor in a 1:1 molar ratio to alkyne.
cleavage products, further supporting the hypothesis that
reduction in coordination sphere nonbonding repulsions
accelerates alkyne hydrothiolation activity. Subsequent
declines in activity can be correlated with visible catalyst
precipitation and are accompanied by significantly reduced
hydrothiolation activity for any aggregated, heterogeneous
species.
Table 7. Charge and Ionic Radius of Lanthanides, Actinides, and
Zirconium32b
a
˚
radius (A)
metal
charge
La
Nd
Th
Sm
U
Y
Lu
Zr
3þ
3þ
4þ
3þ
4þ
3þ
3þ
4þ
1.160
1.109
1.09
1.079
1.05
1.019
0.977
0.890
Ancillary Ligand and Metal Effects on Catalytic Activity.
Metal and ancillary ligation exert a pronounced influence on
hydrothiolation activity, with decreased nonbonding inter-
actions around the metal invariably enhancing the hydro-
thiolation activity. In increasing the ionic radius from Lu to
Sm (Table 7), a 20-fold increase in initial activity is observed
(Table 2, entries 2 and 3), similar to trends observed in
analogous lanthanide-mediated alkyne hydroalkoyxlation.13i,m
a Ionic radius reported for octacoordinate, trivalent lanthanides and
nonacoordinate, tetravalent actinides and zirconium.
thiol-mediated Cp* and Me2SiCp00 protonolysis occurs
2
rapidly, leaving the metal centers open to aggregation into
insoluble, presumably μ-SR species. Greater covalency in
actinide versus lanthanide bonding51d,e undoubtedly is a
factor in the greater resistance of the Cp*2An< versus
Cp*2Ln- complexes to ring cleavage. Consistent with lit-
erature reports on related processes,10e metal ionic radius10a,32
also exerts a large influence on catalyst thiolytic stability, with
smaller ions exhibiting greater resistance to precipitation
despite similar susceptibility to the first Cp* ligand cleavage.
This is presumably a result of smaller, more sterically con-
gested coordination spheres resulting in less favorable ag-
gregation and slower protonolysis of the second Cp* ligand.
The organoactinide complexes Cp*2Th[CH2(TMS)]2 and
Cp*2U[CH2(TMS)]2 exhibit greater protonolytic stability
versus Cp*2SmCH(TMS)2, even after initial ligand cleavage,
likely for similar reasons of metal size and greater charge/
radius ratio.
Monitoring thereactionprogress forthe organolanthanide-
and organoactinide-mediated hydrothiolation of 1-hexyne (7)
by 1-pentanethiol (10) reveals interesting reactivity trends
with regard to catalyst structure. An initial surge of activity
is often observed both at room temperature and at 120 °C
with the Sm and Lu catalysts, possibly the result of transi-
tory, less aggregated, catalytic species, whereas no initial
phase of heightened activity is observed with the aforemen-
tioned organoactinide complexes, likely reflecting the
bulky ligation. Upon further heating, regions of invariant
rate are observed, with both types of catalyst displaying
periods of no obvious change in catalyst structure. Subse-
quent increases in activity correlate with observed ligand
˚
A comparison of U and Th (1.05 and 1.09 A, respectively)
catalysts evidences an almost 6ꢀ increase in hydrothiolation
rate (Figure 6)
In constraining the organoactinide ancillary ligands from
Cp*2 to Me2SiCp00 , the opening of the coordination sphere
2
results in a >12ꢀ increase in activity (Figure 6), similar to that
observed in organoactinide-mediated hydroamination.46,47
Furthermore, as the cyclopentadienyl ligands in Cp*2Sm-,
Cp*2An<, and Me2SiCp002An< (An = U and Th) are
removed by protonolysis, an increase in hydrothiolation rate
is observed, prior to catalyst precipitation (Figure 5). As a
result, the steric properties of the catalytically active species
are the dominant factor in dictating the hydrothiolation
activity of homogeneous lanthanide and actinide catalysts.
Substrate Scope and Conversion for Intermolecular Alkyne
Hydrothiolation. Both the electronic and steric characteris-
tics of the thiol substrates are found to exert a significant
influence on hydrothiolation conversion rates, with steric
factors exerting a greater influence than electronic factors.
The results of organosamarium-mediated hydrothiolation of
1-hexyne (Table 3) indicate that thiol nonbonding repulsions
dramatically influence catalytic turnover. This is consistent
with turnover frequencies observed in organothorium-
mediated13b and organozirconium-mediated6a alkyne hy-
drothiolation where the activity dependence on thiol encum-
brance is attributed to thiolate ligation. Despite the increased
nonbonded repulsions imposed by thiophenol (16) and
benzylmercaptan (14) versus 1-pentanethiol (10), moderate-
to-high conversions are observed, arguing for a thiol electronic

6318 Organometallics, Vol. 29, No. 23, 2010
Weiss et al.
Figure 8. Structure of known Cp*2Sm-allyl complexes.55
Figure 7. Insertive transition state for the formation of
Markovnikov (A) and anti-Markovnikov (B) hydrothiolation
products.
effect on hydrothiolation activity. The high activity of benzyl-
mercaptan (14), despite the moderate steric encumbrances,
indicates an optimization of both steric and electronic factors.
On varying alkyne substituents, both electronic and steric
factors are found to influence catalytic activity. Similar to
organozirconium-mediated alkyne hydrothiolation,6a ali-
phatic, R-disubstituted alkynes appear to exhibit moderately
lower hydrothiolation activity versus similar R-monosubsti-
tuted alkynes. In switching to a β-disubstituted alkyne, a
similar low conversion is observed. The addition of aroma-
ticity to either the R- or β-position increases the conversion,
suggesting electronic effects or possible preorganization
effects. While this may stem from a change in the alkyne
electronic character, it could also result from the slight
reduction in steric encumbrance in phenyl versus cyclohexyl.
Regioselectivity of Intermolecular Terminal Alkyne Hydro-
thiolation. The observed quantities of anti-Markovnikov hy-
drothiolation products provide evidence for a known, free
radical pathway5b-f in kinetic competition with the catalytic
pathway. While most thiols afford excellent Markovnikov
selectivities, the samarium-mediated hydrothiolations of
1-hexyne (7), cyclohexylmercaptan (12), and thiophenol (16)
yield non-negligible quantities of anti-Markovnikov products.
While the lower selectivities of the secondary thiols might
suggest that nonbonded repulsive effects in the insertive
transition state (Scheme 1) could afford anti-Markovnikov
products, the congested metal center coordination sphere
(Figure 7B) suggests that this is unlikely. More probable is
the intrusion of a previously reported, free radical side
reaction5b-f,6a,52,53 in kinetic competition with the metal-
centered catalytic pathway. The low conversion/activity using
cyclohexylmercaptan (12) is consistent with the analogous
organothorium-13b and organozirconium-mediated hydrothio-
lation results.6a This result argues that the lower Markovnikov
selectivity results from the low catalytic activity of cyclohexyl-
mercaptan (12) in competition with the free radical process.
While thiophenol (16) gives moderate conversion to
Markovnikov product, a mixture of anti-Markovnikov prod-
ucts is still observed in both the Sm- and Th-mediated
hydrothiolation reactions. This likely reflects the weaker
RS-H bond39a,c more effectively initiating the radical side
reactions (eq 8). Variations in hydrothiolation selectivity are
also observed as a function of the alkyne substituent, with aryl
and nonconjugated substituents affording lower Markovnikov
selectivity. These lower selectivities likely arise from an
enhanced ability to stabilize free radicals (eqs 9 and 10) via
Figure 9. Proposed insertive transition state for the formation
of Markovnikov product (A) and a possible, competing transi-
tion state for the formation of anti-Markovnikov product (B)
with 1-ethynylcyclohexene (24).
Scheme 2. Proposed Pathway for the Scrambling of Deuterium
between Terminal Alkynes and Thiols
delocalization of the radical through conjugation with the
vinyl sulfide.
Further support for the contention that the anti-Markovnikov
side product is not primarily the result of a metal-
catalyzed process but rather arises from a known radical
pathway comes from the effects of radical inhibitors. On
introducing γ-terpinene as a radical inhibitor,54 the yield of
anti-Markovnikov products is substantially suppressed, by
3-14ꢀ. Despite this modification, the 1-ethynylcyclohexene
hydrothiolation (Table 5, entry 4) yields only moderate
selectivity, suggesting the possibility that the low selec-
tivity may also reflect the intrinsic selectivity of the catalytic
reaction. The deep purple color (see Supporting Information) of
the reaction mixture suggests an extended π-interaction: a
possible interaction between 1-ethynylcyclohexene (24) and
(52) Silva, M. S.; Lara, R. G.; Marczewski, J. M.; Jacob, R. G.;
~
Lenardao, E. J.; Perin, G. Tetrahedron Lett. 2008, 49, 1927–1930.
(53) Control experiments performed without catalyst evidence the
formation of free radical-derived anti-Markonikov products under
reaction conditions presented in this study.
(54) The radical inhibitor is added in a 1:1 molar ratio with alkyne.

Article
Organometallics, Vol. 29, No. 23, 2010 6319
Scheme 3. Thiol (A) and Alkyne (B) Protolytic/Deuterolytic Pathways for the Formation of Product Isotopomers
the Sm center similar to that observed in Cp*2Sm-allyl com-
plexes (Figure 8).55 While a favorable interaction between the
cyclohexene substituent and the electrophilic metal center in the
insertive transition state might be expected to yield E anti-
Markovnikov product (Figure 9B), the approximately equimo-
lar formation of both E and Z isomers argues against this
pathway. Alternatively, the imperfect selectivity of 1-ethynyl-
cyclohexene could result from a combination of early catalyst
deactivation and an alkyne known to be highly active toward
radical hydrothiolation.6a
lanthanide- and actinide-heteroelement bonds suggests a
pathway such as shown in Scheme 2. Interestingly, the more
rapid formation of the product isotopomers in lanthanide- and
actinide-mediated hydrothiolation than in zirconium-mediated
hydrothiolation is consistent with the more polar bonding and
larger ionic radii of lanthanide and actinide complexes, as
well as lanthanide and actinide complexes exhibiting a lower
protonolytic/deuterolytic barrier.51e Bond enthalpy estimates
indicate that the protonolytic detachment of alkyne from
organo-Th or organo-Sm complexes is ca. -24 and -22 kcal/
mol, respectively (eq 11). Due to the Markovnikov selectivity58
and exothermicity of thiol-mediated protonolysis of metal-
alkynyl bonds,8i,57 the
Deuterium Labeling. Isotopic labeling of the alkyne yields
insights into the hydrothiolation mechanism. The apparent
kH/kD = 1.4(0.1) and 1.35(0.1) for the organo-Sm and
organo-Th catalysts, respectively, is consistent with a sec-
ondary kinetic isotope effect in a turnover-limiting insertion
mechanism (Scheme 1) and is similar to that reported for
analogous insertion reactions.56 The observation of 27-dE
product early in the reaction is consistent with thiol-
mediated protonolysis. As the reaction progresses, increas-
ing quantities of other product isotopomers form, corre-
sponding to redistribution of the alkyne 2H label. The
observed 2H exchange between phenylacetylene-d (26-d)
RS-H þ M-C tCR0 f M- SR
þ H-C tCR0 M ¼ Th=Sm
ð11Þ
metal-alkynyl h metal-thiolate equilibrium should strongly
favor the corresponding thiolates. In the 5- and 32-mediated
hydrothiolation of phenylacetylene-d (26-d) by 10, the forma-
tion of primarily 27-dE further supports the insertion/thiol-
mediated protonolysis mechanism (Scheme 3A). The observa-
tion of small quantities of 27-dZ and 27 early in the reaction
demonstrates the rapid nature of deuterium/proton scrambling
between the alkyne and thiol positions.
t
and BuSH (33), prior to significant catalytic turnover, as
2
well as negligible H migration in the absence of catalyst,
strongly supports a metal complex-mediated pathway, in-
dependent of the hydrothiolation catalytic cycle.
While alkyne deuterolysis of the M-vinyl product from
the lanthanide or actinide center could result in 2H delivery
to the Z product position (e.g., Scheme 3B), it seems more
likely to originate from thiol-mediated deuterolysis of prod-
ucts bound to the metal center (eq 12), because of the RSD
detected in situ by 2H NMR and REH (E = O and S)
protonolysis pathways in analogous organozirconium-
mediated hydrothiolation6a and lanthanide-mediated hydro-
alkoxylation processes.13d,g,i,m
Hydrogen/deuterium scrambling involving terminal alkynes
has been previously observed in analogous organoactinide-
mediated hydrothiolation,13b lanthanide-mediated hydroalkoxyl-
ation,13i and organozirconium-mediated hydrothiolation,6a as a
result of the type of metal-alkynyl/metal-heteroelement equi-
libration previously reported for organouranium complexes.8h,i
The known protonolytic reactivity of terminal alkynes8i,57 with
(55) Evans, W. J.; Ulibarri, T. A.; Ziller, J. W. J. Am. Chem. Soc.
1990, 112, 2314–2324.
(56) Tobisu, M.; Nakai, H.; Chatani, N. J. Org. Chem. 2009, 74,
5471–5475.
(57) (a) Barnea, E.; Andrea, T.; Berthet, J.-C.; Ephritikhine, M.;
Eisen, M. S. Organometallics 2008, 27, 3103–3112. (b) Nishiura, M.; Hou,
Z. J. Mol. Catal. A: Chem. 2004, 213, 101–106. (c) Nishiura, M.; Hou, Z.;
Wakatsuki, Y.; Yamaki, T.; Miyamoto, T. J. Am. Chem. Soc. 2003, 125,
1184–1185. (d) Wang, J.; Kapon, M.; Berthet, J. C.; Ephritikhine, M.; Eisen,
M. S. Inorg. Chim. Acta 2002, 334, 183–192. (e) Heeres, H. J.; Teuben, J. H.
Organometallics 1991, 10, 1980–1986.
(58) As is discussed earlier, Markovnikov selectivity is suggestive of
alkyne insertion into the M-SR bond.

6320 Organometallics, Vol. 29, No. 23, 2010
Weiss et al.
Scheme 4. Proposed Turnover-Limiting Alkyne Insertion (k2) Pathway for Organosamarium-Mediated Terminal Alkyne
Hydrothiolation
LnSm-vinylic product from the metal after the turnover-
limiting step. This is consistent with lanthanide-mediated
hydroalkoxylation and organoactinide-mediated hydrothiola-
tion mechanistic patterns but stands in contrast to organo-
zirconium-mediated alkyne hydrothiolation,6a where thiol pro-
tonolysis of the Zr-vinylic product from the metal center is slow
enough to be kinetically relevant. Differences between orga-
nozirconium and organo-f-element hydrothiolation likely
result from the greater covalency in organozirconium
bonding,51e affording more sluggish protonolysis. While orga-
noactinide complexes are experimentally more covalent than
organolanthanide complexes,51d these slight differences are still
rather modest and not observable in thiol protonolysis under
the present reaction conditions.
Summary
Kinetic and Mechanistic Data for Organolanthanide- and
Organoactinide-Mediated Intermolecular Alkyne Hydrothio-
lation
1.
Approximate empirical rate law: rate
=
kobs[catalyst]1[alkyne]1[thiol]0
2. Markovnikov selectivity
3. Hydrothiolation conversion heavily dependent upon
thiol steric encumbrance
4. Alkyne RCtC-H/D isotopic labeling yields kH/kD
1.40(0.1) and 1.35(0.1) for samarium and thorium, respectively
5. A single product isotopomer is predominant in the early
stages of turnover
=
6. Multiple product isotopomers are produced throughout
the reaction
7. Deuterium/hydrogen scrambling between alkyne
Conclusions
RCtC-H/D and thiol RS-H/D is observed
Organolanthanide and organoactinide complexes are
Markovnikov-selective catalysts for the hydrothiolation of
terminal alkynes under homogeneous conditions. Catalyst
aggregation is observed but can be ameliorated by using
smaller ionic radius metals and sterically encumbering Cp-
based ancillary ligation. While anti-Markovnikov products
are occasionally observed under reaction conditions, these
are often efficiently suppressed by the addition of a radical
inhibitor. On the basis of kinetic experiments, deuterium
labeling, and other results, an insertion/protonolysis mech-
anism in which alkyne insertion is turnover-limiting followed
by rapid thiol protonolysis is proposed for both lanthanide-
and actinide-mediated alkyne hydrothiolation. Comparison
of different metal ions, ligation, and substrates reveals that
nonbonding repulsions largely dominate hydrothiolation
catalytic activity.
8. Thiol protonolysis of An-/Ln-C products and alkyne
release from the metal center is predicted to be highly exothermic
9. Insertion of alkyne into M-SR (M = Sm or Th) bonds
is predicted to be exothermic.
The activation of catalyst upon addition of thiol to pre-
cursor amides and alkyls is very rapid and quantitative by 1H
NMR, consistent with similar observations in organolantha-
nide-mediated hydroamination11g and hydroalkoxylation13g,i,m
(but not in hydrophosphination).12b-e This is indicative of the
relatively strong M-SR (M = Ln and An) and H-C bonds.
The absence of significant HDC(TMS)2 in the in situ 1H and 2H
NMR spectra of the deuterium-labeling experiments indicates
that thiol protonolysis is significantly more rapid than alkyne
protonolysis.
The high Markovnikov selectivity, empirical rate law,
deuterium-labeling results, and bond enthalpy considera-
tions are consistent with an insertion/protonolysis pathway
for organosamarium-mediated alkyne hydrothiolation.
Here alkyne insertion into the LnSm-SR bond (Scheme 4,
k2) is turnover-limiting and subsequent thiol LnSm-C pro-
tonolysis (Scheme 4, k3) is rapid (i.e., k3 . k2), with a catalyst
metal-thiolate resting state (i.e., k1 > k-1). The invariance
of rate with respect to [thiol] under the present experimental
conditions indicates very rapid protonolytic cleavage of the
Acknowledgment. The National Science Foundation
(CHE-0809589) is gratefully acknowledged for financial
support of this research. We also thank Mr. M. Weberski
for helpful discussions.
Supporting Information Available: Kinetic data, thermody-
namic calculations, NMR spectra, and digital images. This
material is available free of charge via the Internet at http://
pubs.acs.org.