Kinetic isotope effects in the thermal C2-C6 cyclization of enyne-allenes: Experimental evidence supports a stepwise mechanism

Article abstract of DOI:10.1021/jo0504971

Kinetic isotope effects suggest that the thermal C²-C ⁶ cyclization of enyne-allenes proceeds through a stepwise diradical mechanism. This is even true if steric bulk at the alkyne terminus is large, contrary to theoretical predictio

Full text of DOI:10.1021/jo0504971

its use in the synthesis of complex carbocycles,9 for DNA
cleavage,10 and recently in photochemical11 applications.
The kinetic competition between the C2-C6 and C2-C7
cyclization can be most conveniently steered through the
proper choice of substituents at the alkyne terminus:
with radical stabilizing groups or bulky groups at C7 the
C2-C6 cyclization is preferred, whereas with hydrogen
or n-alkyl substituents the C2-C7 reaction mode is
observed. Moreover, it has been emphasized that ben-
zannulation12 and oxyanion substitution at the allene13
provide a kinetic advantage for the C2-C6 cyclization.
Mechanistic and theoretical evidence is clearly in favor
of the intermediacy of a fulvenyl diradical in the course
of the C2-C6 cyclization, although most examples in the
literature could also be reconciled with a concerted ene
or Diels-Alder reaction.7,10 Certainly, the reaction does
not involve a polar transition state or polar intermedi-
ates.14 To date, the most convincing evidence for a
stepwise mechanism comes from direct trapping of the
fulvenyl diradical through hydrogen transfer,7e a kinetic
indifference in stepwise Diels-Alder processes,7b and
from computational studies.7e,8 Due to the wide variation
of substituents tolerated in the C2-C6 cyclization, how-
ever, there may be a changeover from the stepwise to
the concerted pathway.15 In this context, Engels16 has
computationally investigated the C2-C6 cyclization lead-
Kinetic Isotope Effects in the Thermal
C2-C6 Cyclization of Enyne-allenes:
Experimental Evidence Supports a
Stepwise Mechanism
Michael Schmittel* and Chandrasekhar Vavilala
Organische Chemie I, FB 8 (Chemie-Biologie), Universita¨t
Siegen, Adolf-Reichwein-Strasse, D-57068 Siegen, Germany
schmittel@chemie.uni-siegen.de
Received March 11, 2005
(7) (a) Schmittel, M.; Strittmatter, M.; Kiau, S. Angew. Chem., Int.
Ed. Engl. 1996, 35, 1843-1845. (b) Schmittel, M.; Strittmatter, M.;
Vollmann, K.; Kiau, S. Tetrahedron Lett. 1996, 37, 999-1002. (c)
Schmittel, M.; Steffen, J. P.; Auer, D.; Maywald, M. Tetrahedron Lett.
1997, 38, 6177-6180. (d) Schmittel, M.; Keller, M.; Kiau, S.; Stritt-
matter, M. Chem. Eur. J. 1997, 3, 807-816. (e) Engels, B.; Lennartz,
C.; Hanrath, M.; Schmittel, M.; Strittmatter, M. Angew. Chem., Int.
Ed. 1998, 37, 1960-1963. (f) Schmittel, M.; Strittmatter, M. Tetrahe-
dron 1998, 54, 13751-13760. (g) Li, H. B.; Zhang, H. R.; Petersen, J.
L.; Wang, K. K. J. Org. Chem. 2001, 66, 6662-6668. (h) Schmittel,
M.; Steffen, J. P.; Maywald, M.; Engels, B.; Helten, H.; Musch, P. J.
Chem. Soc., Perkin Trans. 2 2001, 1331-1339. (i) Yang, Y. H.; Petersen,
J. L.; Wang, K. K. J. Org. Chem. 2003, 68, 5832-5837. (j) Yang, Y. H.;
Petersen, J. L.; Wang, K. K. J. Org. Chem. 2003, 68, 8545-8549.
(8) (a) Engels, B.; Hanrath, M. J. Am. Chem. Soc. 1998, 120, 6356-
6361. (b) Schreiner, P. R.; Prall, M. J. Am. Chem. Soc. 1999, 121, 8615-
8627. (c) Cramer, C. J.; Kormos, B. L.; Seierstad, M.; Sherer, E. C.;
Winget, P. Org. Lett. 2001, 3, 1881-1884. (d) de Visser, S. P.; Filatov,
M.; Shaik, S. Phys. Chem. Chem. Phys. 2001, 3, 1242-1245. (e) Stahl,
F.; Moran, D.; Schleyer, P. V.; Prall, M.; Schreiner, P. R. J. Org. Chem.
2002, 67, 1453-1461. (f) Prall, M.; Schreiner, P. R. J. Org. Chem. 2002,
67, 1453-1461. (g) Schreiner, P. R.; Navarro-Vazquez, A.; Prall, M.
Acc. Chem. Res. 2005, 38, 29-37.
Kinetic isotope effects suggest that the thermal C2-C6
cyclization of enyne-allenes proceeds through a stepwise
diradical mechanism. This is even true if steric bulk at the
alkyne terminus is large, contrary to theoretical predictions
by Engels.
Thermal cycloaromatizations of enediynes (Bergman)1
and enyne-allenes (Myers-Saito, C2-C7)2 have elicited
extensive attention over the past decade,3 as the result-
ant diradicals represent key intermediates in the mode
of action of natural enediyne antitumor antibiotics.4 In
1995, a competing thermal reaction mode of enyne-
allenes (see Scheme 1) was disclosed.5,6 Since then, the
so-called C2-C6 cyclization has been extensively studied
mechanistically7 and theoretically,8 in particular due to
(9) (a) Zhang, H.-R.; Wang, K. K. J. Org. Chem. 1999, 64, 7996-
7999. (b) Wang, K. K.; Zhang, H.-R.; Petersen, J. L. J. Org. Chem. 1999,
64, 1650-1656.
(1) (a) Bergman, R. G.; Jones, R. R. J. Am. Chem. Soc. 1972, 94,
660-661. (b) Bergman, R. G. Acc. Chem. Res. 1973, 6, 25-31.
(2) (a) Myers, A. G.; Kuo, E. Y.; Finney, N. S. J. Am. Chem. Soc.
1989, 111, 8057-8059. (b) Nagata, R.; Yamanaka, H.; Okazaki, E.;
Saito, I. Tetrahedron Lett. 1989, 30, 4995-4998.
(3) Selected reviews: (a) Maier, M. E. Synlett 1995, 13-26. (b) K.
K. Wang, Chem. Rev. 1996, 96, 207-222. (c) Grissom, J. W.; Gunawar-
dena, G. U.; Klingberg, D.; Huang, D. Tetrahedron 1996, 52, 6453-
6518. (d) Basak, A.; Mandal, S.; Bag, S. S. Chem. Rev. 2003, 103, 4077-
4094. (e) Wenk, H. H.; Winkler, M.; Sander, W. Angew. Chem., Int.
Ed. 2003, 42, 502-528. (f) Rawat, D. S.; Zaleski, J. M. Synlett 2004,
3, 393-421. (g) Klein, M.; Walenzyk, T.; Ko¨nig, B. Collect. Czech. Chem.
Commun. 2004, 69, 945-965.
(4) (a) Nicolaou, K. C.; Dai, W.-M. Angew. Chem., Int. Ed. Engl.
1991, 30, 1387-1416. (b) Borders, D. B.; Doyle, T. W. Enediyne
Antibiotics as Antitumor Agents; Marcel Dekker: New York, 1995.
(5) Schmittel, M.; Strittmatter, M.; Kiau, S. Tetrahedron Lett. 1995,
36, 4975-4978.
(6) Equally, alternative thermal biradical cyclizations of enediynes
are under investigation: Prall, M.; Wittkopp, A.; Schreiner, P. R. J.
Phys. Chem. A 2001, 105, 9265-9274.
(10) (a) Schmittel, M.; Kiau, S.; Siebert, T.; Strittmatter, M.
Tetrahedron Lett. 1996, 37, 7691-7694. (b) Schmittel, M.; Maywald,
M.; Strittmatter, M. Synlett 1997, 165-166.
(11) (a) Schmittel, M.; Rodr´ıguez, D.; Steffen, J.-P. Angew. Chem.,
Int. Ed. 2000, 39, 2152-2155. (b) Schmittel, M.; Mahajan, A. A.;
Bucher, G. J. Am. Chem. Soc. 2005, 127, 5324-5325.
(12) Wenthold, P. G.; Lipton, M. A. J. Am. Chem. Soc. 2000, 122,
9265-9270.
(13) Brunette, S. R.; Lipton, M. A. J. Org. Chem. 2000, 65, 5114-
5119.
(14) (a) Schmittel, M.; Maywald, M. Chem. Commun. 2001, 155-
156. (b) Schmittel, M.; Strittmatter, M.; Kiau, S. Angew. Chem., Int.
Ed. Engl. 1996, 35, 1843-1845.
(15) For other ene cyclizations, the changeover from concerted to
stepwise mechanism has equally been discussed: Mikami, K.; Ohmura,
H.; Yamanaka, M. J. Org. Chem. 2003, 68, 1081-1088. Lu, X. Org.
Lett. 2004, 6, 2813-2815 and refs therein.
(16) Musch, P. W.; Engels, B. J. Am. Chem. Soc. 2001, 123, 5557-
5562.
10.1021/jo0504971 CCC: $30.25 © 2005 American Chemical Society
Published on Web 05/04/2005
J. Org. Chem. 2005, 70, 4865-4868
4865

SCHEME 1. Thermal C2-C7 (Myers-Saito) and C2-C6 Cyclization of Enyne-allenesa
a The latter reaction leads to a formal ene or formal Diels-Alder (DA) products.
SCHEME 2. Mechanistic Options for the Thermal
ing to ene products. On the basis of calculations, he
inferred that there is a transition from the stepwise to
concerted pathway with a tert-butyl group at the alkyne
terminus. This prediction seems to be in accordance with
the experimental finding that C2-C6 ene reactions indeed
proceed much cleaner with bulky groups than with aryl
groups at the alkyne terminus.17 For the concerted ene
reaction, the kinetic isotope effect kH/kD was calculated
to be 2-2.3,16 whereas for the diradical mechanism
kH/kD should be close to unity. Herein, we describe an
experimental study of the kinetic isotope effect that
demonstrates that, even with sterically extremely bulky
groups, the observed ene reaction proceeds in a stepwise
manner, lending further support to a diradical mecha-
nism of the C2-C6 cyclization.
Ene Reaction of Enyne-allenes
1
13C NMR, IR, and HRMS. Importantly, in the H NMR,
the methoxy group of 2a at δ 3.78 ppm was well
separated from the methoxy group signal of 1a at δ 3.81
ppm.
Results and Discussion
To evaluate the kinetic isotope effect, we have chosen
the benzannulated enyne-allene 1a and its deuterium
analogue 1b that are both characterized by a very bulky
substituent at the alkyne terminus and an alkyl group
at the allene terminus for hydrogen transfer. Prior
screening of a wide variety of substituents R1-R3 had
indicated that other enyne-allenes 1 were less suited due
to yields for the ene reaction of less than 85%.
Preparation of 1a,b started out with a Sonogashira
cross coupling of o-bromobenzaldehyde (3) with triiso-
propylsilyl acetylene to afford 4 in 83% yield (Scheme 3).18
Addition of BrMgC≡C-R (R ) n-Bu, -CD2CH2CH2CH3;
cf. Scheme 4) provided the propargyl alcohols 5a,b.19
Reaction of 5a,b with acetic anhydride at room temper-
ature in the presence of 4-N,N-(dimethylamino)-pyridine
(DMAP) afforded the corresponding propargyl acetates20
6a,b. Enyne-allenes 1a,b were finally received through
a Pd-promoted reaction of p-AnZnCl21 with 6a,b at -60
°C. 1H and 13C NMR, IR, and HRMS convincingly
supported the structural assignment of 1a,b.
Kinetic isotope effect (KIE) measurements are a pow-
erful diagnostic tool for the distinction between stepwise
and concerted mechanisms.22 The observation of a large
KIE (kH/kD > 2) should be indicative of a hydrogen
transfer in the rate-limiting step and has often been
taken as evidence for a concerted mechanism,23 while
absence of a substantial deuterium KIE was considered
to be the signature of a stepwise mechanism.24
Thermolysis of 1a,b was carried out in closed vessels
at 100.0 ( 0.1 °C in toluene after a first evaluation of
the thermal reactivity had been made by differential
scanning calorimetry. A kinetic isotope effect kH/kD
)
1.174 ( 0.039 (at 100.0 ( 0.1 °C) was determined from
six rate constants for thermal cyclization of enyne-allene
1a and its deuterated analogue 1b (Table 1).
(22) (a) Wiberg, K. B. Chem. Rev. 1955, 55, 713-743. (b) Collins, C.
J., Brown, N. S., Eds. Isotope Effects in Chemical Reactions; von
Nostrand Reinhold: New York, 1970. (c) Bell, R. P. The Proton in
Chemistry, 2nd ed.; Cornell University Press: Ithaca, NY, 1974. (d)
Stephenson, L. M.; Grdina, M. J.; Orfanopoulos, M. Acc. Chem. Res.
1980, 13, 419-425. (e) Melander, L.; Saunders, W. H., Jr. Reaction
Rates of Isotopic Molecules; Wiley-Interscience: New York, 1980. (f)
Singleton, D. A.; Hang, C.; Szymanski, M. J.; Greenwald, E. E. J. Am.
Chem. Soc. 2003, 125, 1176-1177.
(23) (a) Dai, S. H.; Dolbier, W. R. Jr. J. Am. Chem. Soc. 1972, 94,
3953-3954. (b) Stephenson, L. M.; Mattern, D. L. J. Org. Chem. 1976,
41, 3614-3619. (c) Beak, P.; Berger, K. J. Am. Chem. Soc. 1980, 102,
3848-3856. (d) Snider, B. B.; Ron, E. J. Am. Chem. Soc. 1985, 107,
8160-8164. (e) Song, Z.; Beak, P. J. Am. Chem. Soc. 1990, 112, 8126-
8134. (f) Adam, W.; Krebs, O.; Orfanopoulos, M.; Stratakis, M.;
Vougioukalakis, G. C. J. Org. Chem. 2003, 68, 2420-2425.
Thermolysis of enyne-allene 1a in toluene furnished
the cyclization product 2a in high yield (91% after
isolation). It was completely characterized using 1H and
(17) Maywald, M. Ph.D. Thesis, Wu¨rzburg, 2000.
(18) Kevin, R. R.; Larock, R. C. J. Org. Chem. 2002, 67, 86-94.
(19) Schmittel, M.; Strittmatter, M.; Schenk, W. A.; Hagel, M. Z.
Naturforsch, B. 1998, 53, 1015-1020.
(20) Borzilleri, R. M.; Weinreb, S. M.; Parvez, M. J. Am. Chem. Soc.
1994, 116, 9789-9790.
(21) Elsevier, C. J.; Stehouwer, P. M.; Westmijze, H.; Vermeer, P.
J. Org. Chem. 1983, 48, 1103-1105.
4866 J. Org. Chem., Vol. 70, No. 12, 2005

SCHEME 3a
a Reaction conditions: (i) TIPS-C≡C-H, Pd(PPh3)2Cl2, CuI, Et3N, 90 °C, 78 h, 83%. (ii) EtMgBr, H-C≡C-nBu, THF, rt, 14 h, 5a:
96%; or EtMgBr, H-C≡C-CD2(CH2)2CH3, THF, rt, 14 h, 5b: 66%. (iii) Ac2O, DMAP, Et3N, CH2Cl2, rt, 12 h, 6a: 92%; 6b: 84%.
SCHEME 4a
SCHEME 5a
a Reaction conditions: (i) LiAlD4, Et2O, 0 °C to rt. (ii) 48% HBr,
H2SO4, 3 h, 62%. (iii) n-BuLi, HMPA, TMS-CtC-H, THF, -78
°C to rt, 12 h, 63%. (iv) KOH, t-BuOH, H2O, 4 h, rt, 45%.
TABLE 1. Rate Constant for the Cyclization of
Enyne-allene in Toluene at 100.0 ( 0.1 °C
a Reaction conditions: (i) p-AnMgBr, ZnCl2 (1 M in diethyl
ether), Pd(PPh3)4, -60 °C to rt, 16 h, 1a: 93%, 1b: 75%. (ii)
toluene, reflux, 14 h, 91%.
a
b
no. of
points
kobsd
kobsd
(10-4 s-1
)
entry
compd
R
(10-4 s-1
)
1
2
3
4
5
6
1a (d0)
1a (d0)
1a (d0)
1b (d2)
1b (d2)
1b (d2)
8
8
8
8
8
8
0.9977
0.9975
0.9979
0.9993
0.9986
0.9972
2.16
2.28
2.23
1.88
1.95
1.85
2.22 ( 0.06
1.89 ( 0.04
SCHEME 6. Visualization of the Two Competing
Transition States in the Diradical Cyclization of 1
that Arise from the Rotation about the Terminal
Allene Terminus
a First-order rate constant. b Average rate constant from three
runs.
The kH/kD ) 1.17 has to be compared with KIEs from
Engels’ calculations and from experimental ene reactions.
Engels16 calculated a kH/kD ) 1.97 for the concerted
thermal ene reaction of 1 (R1 ) t-Bu, R2 ) R3 ) H), while
experimental kH/kD for concerted ene reactions range
from 2.3 to 3.2.23e,25 As such, the observed kH/kD ) 1.17
clearly suggests a stepwise mechanism. While, it is too
small to represent a primary kinetic isotope effect, the
observed KIE is notably higher than kH/kD ) 1.00-1.04
as found by Singleton and Hang26 for a stepwise ene
reaction. Also, hyperconjugation cannot explain a kH/kD
) 1.17, though it is generally accepted as the major
contributor to â-deuterium secondary kinetic isotope
effects for reactions with radicaloid transition states and
for equilibrium isotope effects involving radicals.15b,27 To
understand this discrepancy, we have analyzed the bona
fide diradical C2-C6 cyclization of 1 (R1 ) Ph, R2 ) R3 )
H) as described in a computational study by Engels.16
C2-C6 diradical cyclizations are special insofar as there
exist two competing pathways, one leading to an s-cis and
the other to an s-trans diradical (Scheme 6).
(24) (a) Chang, M. H.; Crawford, R. J. Can. J. Chem. 1981, 59, 2556-
2567. (b) Song, Z.; Chrisope, D. R.; Beak, P. J. Org. Chem. 1987, 52,
3938-3940. (c) Jacobsen, J. R.; Cochran, A. G.; Stephans, J. C.; King,
D. S.; Schultz, P. G. J. Am. Chem. Soc. 1995, 117, 5453-5461. (d)
Singleton, D. A.; Hang, C. J. Am. Chem. Soc. 1999, 121, 11885-11893.
(e) Vassilikogiannakis, G.; Stratakis, M.; Orfanopoulos, M.; Foote, C.
S. J. Org. Chem. 1999, 64, 4130-4139. (f) Singleton, D. A.; Hang, C.
J. Org. Chem. 2000, 65, 895-899. (g) Leach, A. G.; Houk, K. N. Org.
Biomol. Chem. 2003, 1, 1389-1403. (h) Baldwin, J. E.; Gallagher, S.
S.; Leber, P. A.; Raghavan, A. Org. Lett. 2004, 6, 1457-1460.
(25) (a) Achmatowicz, O., Jr.; Szymoniak, J. J. Org. Chem. 1980,
45, 4774-4776. (b) Stephenson, L. M.; Orfanopoulos, J. Org. Chem.
1981, 46, 2201-2202. (c) Song, Z.; Chrisope, D. R.; Beak, P. J. Org.
Chem. 1987, 52, 3938-3940.
This is a consequence of the rotation of the terminal
allene carbon in order to maximize overlap of the incipi-
ent radical center with the fulvene unit. In a first
(26) Singleton, D. A.; Hang, C. J. Am. Chem. Soc. 1999, 121, 11885-
11893.
(27) Sunko, D. E.; Hehre, W. J. Prog. Phys. Org. Chem. 1983, 16,
205-246.
J. Org. Chem, Vol. 70, No. 12, 2005 4867

1H); 13C NMR (100 MHz, CDCl3) δ 11.3, 13.9, 18.7, 22.6, 29.9,
30.1, 55.2, 95.6, 95.9 105.1, 109.3, 113.9, 121.3, 126.1, 126.4,
127.2, 128.1, 128.5, 133.0, 136.8, 158.8, 207.0; MS-EI (70 eV)
m/z 458.3 [M+]; HRMS calcd for C31H42OSi 458.300, found
458.301.
approximation, both pathways should exhibit the same
C(HR2)-H elongation due to equal hyperconjugation
effects in the transition state. However, the calculations
reveal that for the s-cis diradical transition state, there
is a notable C(HR2)-H elongation to 1.108 Å that is less
pronounced in the s-trans transition state (1.099 Å) of 1
(R1 ) Ph, R2 ) R3 ) H). Although this difference (ca. 0.01
Å) seems to be small, one has to keep in mind that the
transition state for the concerted ene reaction of 1 (R1 )
t-Bu, R2 ) R3 ) H) is characterized by only a slightly
increased C(HR2)-H bond (l ) 1.190 Å), resulting in a
calculated kH/kD ) 1.97. How can one, however, under-
stand the difference in the C(HR2)-H elongation of the
s-cis and s-trans transition state structures? We suggest
that in the bona fide diradical cyclization of 1 (R1 ) Ph,
R2 ) R3 ) H), a slight C(HR2)-H elongation results in
the s-cis transition state due to a weakly bonding
C7‚‚‚‚‚H interaction that is not possible in the s-trans
pathway. Therefore, the experimental kH/kD ) 1.17 for
1a,b is slightly increased due to a C(HR2)-H stretching
that is only observable in the s-cis transition state.
Further investigation, however, will have to await high-
level calculations on the cyclization of 1a,b that are
beyond the scope of this paper.
Conclusion. The present study supports the view that
the C2-C6 cyclization proceeds through a stepwise dirad-
ical mechanism. This is even true if steric bulk at the
alkyne terminus is large, contrary to theoretical predic-
tions by Engels.16 One must state that these conclusions
were drawn on the basis of the classical interpretation
of KIEs, as the role of nonstatistical effects has not been
taken into consideration. Hence, further insight may
become possible through molecular dynamics simula-
tions.22f
Triisopropyl-{2-[3-(4-methoxyphenyl)-[4,4-2H2]-hepta-
1,2-dienyl]-phenylethynyl}-silane (1b). Procedure as de-
scribed for the synthesis of 1a, yield 75%: IR (KBr) 3061, 2942,
2864, 2151, 1929, 1606, 1510, 1444, 1383, 1297, 1089, 883, 835
cm-1 1H NMR (400 MHz, CDCl3) δ 0.93 (t, J ) 7.3 Hz, 3H),
;
1.11 (bs, 21H), 1.43 (sextet, J ) 7.1 Hz, 2H), 1.53-1.65 (m, 2H),
3.81 (s, 3H), 6.88 (d, J ) 8.8 Hz, 2H), 7.13 (td, J ) 7.8, 1.3 Hz,
1H), 7.15 (s, 1H), 7.23 (td, J ) 7.8, 1.3 Hz, 1H), 7.38 (d, J ) 8.8
Hz, 2H), 7.45 (dd, J ) 7.8, 1.3 Hz, 1H), 7.49 (dd, J ) 7.8, 1.3 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 11.3, 13.9, 18.7, 22.6, 29.2
(CD2), 29.8, 55.2, 95.6, 95.9, 105.1, 109.2, 113.9, 121.3, 126.0,
126.4, 127.2, 128.1, 128.5, 133.0, 136.8, 158.7, 207.0; MS-EI (70
eV) m/z 460.3 [M+]; HRMS calcd for C31H40D2OSi 460.313, found
460.313.
Triisopropyl-{2-[1-(4-methoxyphenyl)-pent-1-enyl]-inden-
1-ylidenemethyl}-silane (2a). Enyne-allene 1a (35 mg, 76
µmol) was dissolved in dry toluene (30 mL), and after degassing
the resulting solution was refluxed for 14 h. After removal of
toluene under reduced pressure and purification by chromatog-
raphy (preparative TLC, silica gel 60 F254, n-pentane), compound
2a was isolated as a yellow oil (32 mg, 91%): IR (KBr) 3053,
2960, 2942, 2865, 1606, 1558, 1509, 1246, 1037, 881 cm-1 1H
;
NMR (400 MHz, CDCl3) δ 0.89 (t, J ) 7.3 Hz, 3H), 1.03 (d, J )
7.5 Hz, 18H), 1.39 (septet, J ) 7.5 Hz, 3H), 1.44 (sextet, J ) 7.3
Hz, 2H), 2.15 (q, J ) 7.3 Hz, 2H), 3.78 (s, 3H), 6.23 (t, J ) 7.3
Hz, 1H), 6.28 (d, J ) 0.8 Hz, 1H), 6.71 (s, 1H), 6.81 (d, J ) 8.8
Hz, 2H), 7.14-7.18 (m, 1H), 7.28 (t, J ) 3.4 Hz, 1H), 7.29 (d, J
) 8.8 Hz, 2H), 7.31 (d, J ) 3.4 Hz, 1H), 7.72 (dd, J ) 7.3, 0.8
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 12.8, 13.8, 19.0, 23.0,
32.2, 55.2, 113.4, 120.4, 122.0, 124.5, 127.3, 128.0, 130.2, 130.8,
132.3, 134.9, 135.3, 135.9, 143.6, 144.2, 155.5, 158.5; MS-EI (70
eV) m/z 458.3 [M+]; HRMS calcd for C31H42OSi 458.300, found
458.298.
Kinetics. The temperature of the bath was maintained at
100.0 ( 0.1 °C. For the determination of the rate constant, an
enyne-allene solution was prepared in a 10 mL volumetric flask.
A portion of this standard solution (0.5 mL) was then pipetted
into the glass ampules, degassed, sealed under a vacuum, and
heated. Samples were removed at known intervals and quenched
by cooling to -40 °C. Then, 0.5 mL of a m-nitroacetophenone
solution in toluene was added to the reaction ampule. After the
removal of the solvent, the 1H NMR integration of selected
hydrogen resonances [methoxy group (δ 3.81 ppm) in enyne-
allene to methyl group in m-nitroacetophenone (δ 2.21 ppm)]
was determined on a 400 MHz 1H NMR apparatus. In general,
eight aliquots were collected. All samples for a given kinetic run
were analyzed under identical conditions. The kinetic results
from three such reaction sets with enyne-allene 1a and 1b are
displayed in Table 1.
Experimental Section
Triisopropyl-{2-[3-(4-methoxyphenyl)-hepta-1,2-dienyl]-
phenylethynyl}-silane (1a). p-Anisole magnesium bromide
solution [prepared from 59.0 mg (2.43 mmol) of Mg and 450 mg
(2.43 mmol) of p-bromoanisole in dry THF (10 mL)] was added
dropwise to a 1 M solution of ZnCl2 (323 mg in 2.35 mL of dry
diethyl ether) at room temperature under a nitrogen atmosphere.
The reaction mixture was stirred for 30 min at room tempera-
ture. Then, it was cooled to -60 °C, and Pd(PPh3)4 (0.35 g, 0.30
mmol) in dry THF (3 mL) was added dropwise. After the reaction
mixture was stirred for 15 min at the same temperature,
propargyl acetate 6a (0.25 g, 0.61 mmol) in dry THF (5 mL) was
added dropwise. After stirring for 16 h at room temperature,
the reaction mixture was quenched with saturated ammonium
chloride solution. The aqueous layer was extracted with diethyl
ether (2 × 25 mL). The combined organic layers were dried
(Na2SO4) and concentrated under reduced pressure. After puri-
fication by column chromatography (silica gel, n-pentane/diethyl
ether ) 19:1), compound 1a was isolated as colorless oil (0.26 g,
93%): IR (KBr) 3059, 2943, 2864, 2151, 1929, 1607, 1510, 1444,
Acknowledgment. We are very much indebted to
the Deutsche Forschungsgemeinschaft and the Fonds
der Chemischen Industrie for continued support of our
research. We thank Dr. Demuth for help with the
manuscript.
1
1388, 1297, 1073, 883, 835 cm-1; H NMR (400 MHz, CDCl3) δ
Supporting Information Available: Experimental pro-
cedures, characterization data for compounds 4, 5a-b, 6a-b, 9
and 10. This material is available free of charge via the
Internet at http://pubs.acs.org.
0.92 (t, J ) 7.3 Hz, 3H), 1.10 (bs, 21H), 1.43 (sextet, J ) 7.1 Hz,
2H), 1.54-1.66 (m, 2H), 2.48-2.61 (m, 2H), 3.81 (s, 3H), 6.87
(d, J ) 8.8 Hz, 2H), 7.13 (td, J ) 7.8, 1.5 Hz, 1H), 7.14 (t, J )
1.8 Hz, 1H), 7.22 (td, J ) 7.8, 1.5 Hz, 1H), 7.38 (d, J ) 8.8 Hz,
2H), 7.45 (dd, J ) 7.8, 1.3 Hz, 1H), 7.48 (dd, J ) 7.8, 1.3 Hz,
JO0504971
4868 J. Org. Chem., Vol. 70, No. 12, 2005