Synthesis of cyclic cis-enediynes from manganese carbyne complexes and α,ω-diynes

Article abstract of DOI:10.1021/om0303799

Cyclic cis-enediynes are readily prepared by a two-step one-pot procedure. The first step is the copper-catalyzed addition of α,ω-diynes to manganese carbyne complexes to give intermediate bis(alkynylcarbene) complexes that rearrange to enediyne complexes below room temperature. In the second step, the free enediyne is released from manganese by photolysis, copper-catalyzed air oxidation, or stoichiometric Cu(II) oxidation. These new procedures have been applied to a variety of five-, six-, and seven-membered-ring cyclic enediynes containing a range of ether, ester, and ketone functional groups.

Full text of DOI:10.1021/om0303799

Organometallics 2003, 22, 3915-3920
3915
Syn th esis of Cyclic cis-En ed iyn es fr om Ma n ga n ese
Ca r byn e Com p lexes a n d r,ω-Diyn es
Charles P. Casey,* Trevor L. Dzwiniel, Stefan Kraft, and Ilia A. Guzei†
Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706
Received May 22, 2003
Cyclic cis-enediynes are readily prepared by a two-step one-pot procedure. The first step
is the copper-catalyzed addition of R,ω-diynes to manganese carbyne complexes to give
intermediate bis(alkynylcarbene) complexes that rearrange to enediyne complexes below
room temperature. In the second step, the free enediyne is released from manganese by
photolysis, copper-catalyzed air oxidation, or stoichiometric Cu(II) oxidation. These new
procedures have been applied to a variety of five-, six-, and seven-membered-ring cyclic
enediynes containing a range of ether, ester, and ketone functional groups.
Sch em e 1
In tr od u ction
Heteroatom-substituted alkynylcarbene complexes
such as (CO)5MdC(OR)CtCR′ are highly reactive,
easily accessible, and useful in a plethora of high-
yielding transformations.1,2 Recently, we prepared non-
heteroatom-substituted alkynyl carbene complexes such
as Cp(CO)2RedC(Tol)CtCPh (1) (Cp ) η5-C5H5, Tol )
4-MeC6H4) to investigate the possibility of [1,3] metal
shifts. However, at 120 °C, the rearrangement of 1 to
Cp(CO)2RedC(Ph)CtCTol (2) was much slower3 than
the unexpected formation of the dimeric E-enediyne
complex [Cp(CO)2Re]2[η2,η2-TolCtC(Ph)CdC(Ph)Ct
CTol] (3) (Scheme 1).4 3 is formed by the regioselective
“tail-to-tail” coupling of the remote alkynyl carbons in
a kinetically second-order process.5 In contrast, Sierra
recently reported the selective “head-to-head” Pd-
catalyzed coupling of (CO)5CrdC(OEt)CtCPh to (E,Z)-
PhCtC(OEt)CdC(OEt)CtCPh.6,7
Sch em e 2
CH2CH2CtCC(Tol)dRe(CO)2Cp (4) readily rearranges
to the cyclic enediyne complex [Cp(CO)2Re]2[η2,η2-
TolCtCC(CH2CH2CH2)dCCtCTol] (5) below room tem-
perature by the coupling of the remote alkynyl carbons
(Scheme 2).5 This straightforward route to enediyne
complexes under mild conditions has potential value in
the synthesis of pharmaceutically interesting ene-
diynes.8
This new rhenium route to enediyne complexes suf-
fers from the high thermal stability of the rhenium
diyne complexes and the high costs associated with
stoichiometric rhenium reactions. To circumvent these
problems, we recently extended this chemistry to the
analogous manganese series.9 Simple manganese al-
kynylcarbene complexes such as Cp(CO)2MndC(Ph)Ct
We recently found that the tethered bis(alkynylcar-
bene) rhenium complex Cp(CO)2RedC(Tol)CtCCH2-
* Corresponding author. E-mail: casey@chem.wisc.edu.
† To whom correspondence should be addressed regarding X-ray
diffraction analysis. Molecular Structure Laboratory, Department of
Chemistry, University of Wisconsin-Madison, 1101 University Ave.,
Madison, WI 53706-1396.
(1) For reviews of heteroatom-substituted alkynylcarbene complexes,
see: (a) Aumann, R.; Nienaber, H. Adv. Organomet. Chem. 1997, 41,
163. (b) Wulff, W. D. In Comprehensive Organometallic Chemistry II;
Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon Press:
Oxford, 1995; Vol. 12, Chapter 5.3. (c) Herndon, J . W. Coord. Chem.
Rev. 1999, 181, 177. (d) Sierra, M. A. Chem. Rev. 2000, 100, 3591. (e)
de Meijere, A.; Schriemer, H.; Duetsch, M. Angew. Chem., Int. Ed.
2000, 39, 3964, and references therein. (f) Herndon, J . W. Tetrahedron
2000, 56, 1257.
(2) For group 7 Fischer alkynylcarbene complexes, see: (a) Weng,
W.; Ramsden, J . A.; Arif, A. M.; Gladysz, J . A. J . Am. Chem. Soc. 1993,
115, 3824. (b) Weng, W.; Arif, A. M.; Gladysz, J . A. Angew. Chem., Int.
Ed. Engl. 1993, 32, 891. (c) Terry, M. R.; Kelly, C.; Lugan, N.; Geoffroy,
G. L.; Haggerty, B. S.; Rheingold, A. J . Organometallics 1993, 12, 3607.
(d) Weng, W.; Bartik, T.; Gladysz, J . A. Angew. Chem., Int. Ed. Engl.
1994, 33, 2199. (e) Casey, C. P.; Kraft, S.; Powell, D. R.; Kavana, M.
J . Organomet. Chem. 2001, 617/ 618, 723.
(6) Sierra, M. A.; del Amo, J . C.; Manchen˜o, M. J .; Go´mez-Gallego,
M. J . Am. Chem. Soc. 2001, 123, 851.
(7) For earlier work on carbene coupling of metal carbene complexes,
see: (a) Casey, C. P.; Anderson, R. L. J . Chem. Soc., Chem. Commun.
1975, 895. (b) Casey, C. P.; Burkhardt, T. J .; Bunnell, C. A.; Calabrese,
J . C. J . Am. Chem. Soc. 1977, 99, 2127. (c) Casey, C. P.; Polichnowski,
S. W. J . Am. Chem. Soc. 1977, 99, 6097. (d) Fischer, H.; Schmid, J . J .
Mol. Catal. 1988, 46, 277. (e) Fischer, H.; Zeuner, S.; Ackermann, K.;
Schmid, J . Chem. Ber. 1986, 119, 1546. (f) Fischer, H.; Zeuner, S.;
Ackermann, K. Chem. Commun. 1984, 684. (g) Hohmann, F.; Siemo-
neit, S.; Nieger, M.; Kotila, S.; Do¨tz, K. H. Chem. Eur. J . 1997, 3, 853.
(8) For reviews of enediynes, see: (a) Nicolaou, K. C.; Smith, A. L.
The Enediyne Anitbiotics in Modern Acetylene Chemistry, Stang, P.
D., Diederich, F., Eds.; VCH: Weinheim, 1995; p 203. (b) Maier, M. E.
Synlett 1995, 13. (c) Grissom, J . W.; Gunawardena, G. U.; Klingberg,
D.; Huang, D. Tetrahedron 1996, 52, 6453. (d) Smith, A.; Nicolaou, K.
C. J . Med. Chem. 1996, 39, 2103. (e) Sander, W. Acc. Chem. Res. 1999,
32, 669. (g) Konig, B. Eur. J . Org. Chem. 2000, 381.
(3) Casey, C. P.; Kraft, S.; Powell, D. R. Organometallics 2001, 20,
2651.
(4) Casey, C. P.; Kraft, S.; Kavana, M. Organometallics 2001, 20,
3795.
(5) (a) Casey, C. P.; Kraft, S.; Powell, D. R. J . Am. Chem. Soc. 2000,
122, 3771. (b) Casey, C. P.; Kraft, S.; Powell, D. R. J . Am. Chem. Soc.
2002, 124, 2584.
10.1021/om0303799 CCC: $25.00 © 2003 American Chemical Society
Publication on Web 08/16/2003

3916 Organometallics, Vol. 22, No. 19, 2003
Casey et al.
Sch em e 3
Sch em e 5
Sch em e 4
Sch em e 6
route. First, we have developed a milder procedure for
synthesis of alkynylcarbene complexes from the copper-
(I)-catalyzed reaction of terminal alkynes with carbyne
complexes; this procedure gets around the use of alkyn-
yllithium reagents. Second, we have developed three
new mild methods for conversion of manganese ene-
diyne complexes to the free enediynes that involve
photolysis or Cu-catalyzed air oxidation or stoichiomet-
ric Cu(II) oxidation. The combination of these advances
has allowed us to synthesize new cyclic enediynes
containing a variety of reactive functionalities.
CTol (7) were readily prepared from [Cp(CO)2Mnt
10
CPh]BCl4 (6) and lithiotolylacetylene (Scheme 3).9,11
The classic Fischer synthesis of carbyne complex 6
involves (1) addition of PhLi to CpMn(CO)3 to give the
isolated acyl manganese complex Cp(CO)2MnCOPhLi,
(2) reaction of the acyl manganese complex with Me3-
SiCl to give the siloxycarbene complex Cp(CO)2Mnd
C(OSiMe3)Ph, and (3) reaction of the siloxycarbene
complex with BCl3 to give 6, which is very temperature
sensitive (Tdec < -20 °C).10
While both the rhenium and manganese alkynyl
carbene complexes were efficiently converted to ene-
diyne metal complexes upon heating above 100 °C, there
were two notable differences between the reactions.
First, while rhenium complexes led exclusively to trans-
enediyne complexes, the manganese analogues gave
mixtures of cis- and trans-enendiyne complexes along
with free enediynes formed from loss of the manganese
fragment.9 Second, while dimerization of rhenium com-
plexes to “tail-to-tail” products was much faster than
[1,3]-rhenium migration, the dimerization of manganese
complex (C5H4Me)(CO)2MndC(Ph)CtCTol (8) was com-
petitive with a [1,3]-manganese shift to give isomer 9
and products were seen resulting from formal “head-
to-head” and “head-to-tail” dimerization: (E/Z)-PhCt
C(Tol)CdC(Tol)CtCPh (10), (E/Z)-TolCtC(Ph)CdC-
(Ph)CtCTol (11), and (E/Z)-PhCtC(Tol)CdC(Ph)Ct
CTol (12) (Scheme 4).9
The attempted synthesis of a tethered bis(alkynyl-
carbene) manganese complex, Cp(CO)2MndC(Ph)Ct
CCH2CH2CH2CtCC(Ph)dMn(CO)2Cp (13), led directly
to the rearranged cyclic enediyne complex [Cp(CO)2Mn]2-
[η2,η2-PhCtCC(CH2CH2CH2)dCCtCPh] (14) (Scheme
5). Thermolysis of the enediyne complex at 100 °C
generated free bis(phenylethynyl)cyclopentene (15) in
moderate yield.9
Resu lts
Cop p er -Ca ta lyzed Ad d ition of Alk yn es to [Cp -
(CO)2Mn tCAr ]+. Previous syntheses of manganese
alkynylcarbene complexes involved addition of reactive
alkynyllithium reagents to cationic manganese carbyne
complexes.8,10 We have now found that alkynylcopper
intermediates generated catalytically from terminal
alkynes, Cu(I) salts, and amine bases react with cationic
carbyne complexes to produce manganese alkynylcar-
bene complexes. Addition of a THF solution of 4-ethyn-
yltoluene and EtNi-Pr2 containing a catalytic amount
of CuBr (10%) and LiI to a yellow CH2Cl2 solution of
[Cp(CO)2MntCTol]BCl4 (16)10 formed the deep red-
brown alkynylcarbene complex Cp(CO)2MndC(Tol)Ct
CTol (17) in 73% yield (Scheme 6). IR spectroscopy
showed that the reaction was complete within a minute
at -35 °C. The carbyne νCO peaks at 2084 and 2042
cm-1 disappeared, and new peaks, assigned to the
manganese alkynylcarbene complex 17, grew in at 1972
and 1921 cm-1. The alkynylcarbene complex 17 was
isolated by column chromatography and characterized
spectroscopically. A study of reaction variables indicated
that higher yields were obtained using EtNi-Pr2 rather
than Et3N as base and using either CuBr or CuI rather
than CuCl as a catalyst; similar yields were obtained
using either phenyl or tolyl carbyne complexes or using
C5H5 or C5H4Me manganese complexes.
Here we report several improvements in the synthesis
of cyclic enediynes by this manganese alkynylcarbene
When the copper-catalyzed addition of tethered alkynes
to manganese alkynes was studied at low temperature,
color changes indicated the formation of tethered bis
alkyne complexes that underwent CdC bond formation
below room temperature to form manganese enediyne
complexes. When a mixture of dipropargyl ether (0.4 mol
(9) (a) Casey, C. P.; Dzwiniel, T. L.; Kraft, S.; Kozee, M. A.; Powell,
D. R. Inorg. Chim. Acta 2003, 345, 320. (b) Kraft. S. Ph.D. Thesis,
University of Wisconsin-Madison, 2001.
(10) Fischer, E. O.; Meineke, E. W.; Kreissl, F. R. Chem. Ber. 1977,
110, 1140.
(11) Ortin, Y.; Coppel, Y.; Lugan, N.; Mathieu, R.; McGlinchey, M.
J . Chem. Commun. 2001, 1690.

Synthesis of Cyclic cis-Enediynes
Organometallics, Vol. 22, No. 19, 2003 3917
Sch em e 7
Sch em e 8
per mol Mn), EtNi-Pr2, and catalytic amounts of CuBr
and LiI was added to a yellow solution of [Cp(CO)2Mnt
CTol]BCl4 (16) in CH2Cl2 at -78 °C, an immediate color
change to deep red-brown occurred, consistent with
formation of the bis(alkynylcarbene) complex Cp-
(CO)2MndC(Tol)CtCCH2OCH2CtCC(Tol)dMn(CO)2-
Cp (18) (Scheme 7). When a sample taken from the
-78 °C reaction mixture was immediately analyzed by
thin-layer chromatography, only the bright red coupled
product [Cp(CO)2Mn]2[η2,η2-TolCtCC(CH2OCH2)dCCt
CTol] (19) was seen. There was no evidence for a dark
red-brown manganese carbene complex such as 18. Slow
warming to room temperature over several hours led
to a noticeably lighter red solution, from which the
bright red enediyne complex 19 was isolated in moder-
ate (38%) yield after silica gel chromatography. Mass
spectroscopic data were consistent with the dimeric
manganese enediyne complex 19. The infrared spectrum
contained two peaks at 1973 and 1907 cm-1, consistent
1
with a dicarbonyl complex. The H NMR spectrum was
similar to those observed for known rhenium enediyne
F igu r e 1. X-ray crystal structure of [Cp(CO)2Mn]2[η2,η2-
PhCtCC(CH2C(CO2Me)2CH2)dCCtCPh] (21). Selected
bond lengths (Å) and angles (deg): Mn(1)-C(6), 1.771(5);
Mn(1)-C(7), 1.784(5); Mn(1)-C(14), 2.088(4); Mn(1)-C(15),
2.138(4); C(14)-C(15), 1.245(5); C(15)-C(16), 1.442(5);
C(16)-C(24), 1.353(5); C(13)-C(14)-C(15), 149.8(4); C(14)-
C(15)-C(16), 154.5(4); C(6)-Mn(1)-C(7), 87.3(2); C(6)-
Mn(1)-C(14), 86.5(2); C(7)-Mn(1)-C(15), 81.1(2); C(14)-
Mn(1)-C(15), 34.3(1).
complexes.5
When the reaction of carbyne complex 16 (16 mM)
with dipropargyl ether, EtNi-Pr2, and catalytic amounts
of CuBr and LiI was monitored by in situ IR spectros-
copy at -70 °C using a ReactIR system, carbyne
complex 16 was consumed within 30 s. However,
because of the similarity of the metal carbonyl stretch-
ing frequencies of the manganese alkynylcarbene com-
plexes (17, νCO ) 1971, 1921 cm-1) and enediyne
complexes (19, νCO ) 1973, 1907 cm-1), it was not
possible to follow the conversion of 18 to 19 by IR
spectroscopy. Attempts to follow the low-temperature
conversion of 18 to 19 by NMR spectroscopy were
unsuccessful due to the formation of trace paramagnetic
impurities.
The greater functional group tolerance of the copper-
catalyzed addition of terminal alkynes to carbyne
complexes compared with the use of alkynyllithium
reagents is illustrated by the reaction of dimethyl
dipropargylmalonate with [Cp(CO)2MntCPh]BCl4 (6).
In this reaction, the initially formed tethered bis-
(alkynylcarbene) complex Cp(CO)2MndC(Ph)CtCCH2-
C(CO2Me)2CH2CtCC(Ph)dMn(CO)2Cp (20) rearranged
below room temperature to the enediyne complex [Cp-
(CO)2Mn]2[η2,η2-PhCtCC(CH2C(CO2Me)2CH2)dCCt
CPh] (21) (Scheme 8). The deep red complex 21 was
isolated by column chromatography in 85% yield and
was characterized both spectroscopically and by X-ray
crystallography (Figure 1).12,13
P h otoch em ica l Relea se of En ed iyn es fr om Ma n -
ga n ese Com p lexes. Earlier we established that release
of the coordinated alkyne could be achieved by ther-
molysis. For example, when the manganese enediyne
complex [Cp(CO)2Mn]2[η2,η2-PhCtCC(CH2CH2CH2)d
CCtCPh] (14) was heated at 90 °C, the free enediyne
1,2-bis(phenylethynyl)cyclopentene (15) was obtained in
70% yield.9 We have now found three milder methods
for release of the enediynes: sunlamp photolysis, cop-
per-catalyzed air oxidation, and stoichiometric Cu(II)
oxidation. Application of the new copper-catalyzed ad-
dition of alkynes to manganese carbyne complexes
together with direct cleavage of the manganese enediyne
complexes with these new cleavage methods has allowed
the synthesis of a variety of cyclic enediynes with a
range of ring sizes and with incorporation of a range of
(13) For related manganese complexes, see: (a) Cash, G. G.;
Pettersen, R. C. J . Chem. Soc., Dalton Trans. 1979, 1630. (b) Lo¨we,
C.; Hund, H.-U.; Berke, H. J . Organomet. Chem. 1989, 378, 211. (c)
Akita, M.; Ishii, N.; Takabuchi, A.; Tanaka, M.; Moro-oka, Y. Orga-
nometallics 1994, 13, 258.
(14) 15 has been prepared previously. J ones, G. B.; Wright, J . M.;
Plourde, G., II; Purohit, A. D.; Wyatt, J . K.; Hynd, G.; Fouad, F. J .
Am. Chem. Soc. 2000, 122, 9872.
(12) See Supporting Information.

3918 Organometallics, Vol. 22, No. 19, 2003
Casey et al.
Sch em e 9
Sch em e 10
Ta ble 2. Syn th esis of En ed iyn es by Air Oxid a tion
of Ma n ga n ese En ed iyn e Com p lexes Der ived fr om
Cop p er -Ca ta lyzed Ad d ition of Diyn es to
Ma n ga n ese Ca r byn e Com p lexes
Ta ble 1. Syn th esis of En ed iyn es by P h otolysis of
Ma n ga n ese En ed iyn e Com p lexes Der ived fr om
Cop p er -Ca ta lyzed Ad d ition of Diyn es to
Ma n ga n ese Ca r byn e Com p lexes
a
b
For preparation of diynes, see Supporting Information. Con-
ditions: 0.42 equiv of diyne per carbyne, CuBr, LiI, EtNi-Pr2,
CH2Cl2, -78 °C. c After purification by column chromatography.
with CuBr, LiI, diyne 22, and EtNi-Pr2 was photolyzed
without isolation, a 67% yield of free enediyne 24 was
obtained (Scheme 9). Other enediynes obtained by
photolytic cleavage are reported in Table 1.
Cop p er -Ca ta lyzed Air Oxid a tion Relea ses En e-
d iyn es fr om Ma n ga n ese Com p lexes. Isolated man-
ganese enediyne complexes purified by column chroma-
tography are air stable as solids and in solution in the
dark. However, in the initial reaction solutions, these
manganese enediyne complexes were readily oxidized
by air to give free enediynes and uncharacterized brown
manganese solids (Table 2).
a
b
For preparation of diynes, see Supporting Information. Con-
ditions: 0.42 equiv of diyne per carbyne, CuBr, LiI, EtNi-Pr2,
CH2Cl2, -78 °C. c After purification by column chromatography.
d
Isomers separated as manganese enediyne complexes.
functional groups. Avoiding isolation of the manganese
enediyne complexes resulted in much higher yields of
enediynes.
We suggest that copper salts remaining in solution
from the copper-catalyzed addition of alkynes to man-
ganese carbyne complexes catalyze the air oxidation of
the manganese enediyne complexes. Copper(I) com-
pounds are readily oxidized to copper(II) species, and
(see below) CuCl2‚2H2O efficiently oxidizes manganese
enediyne complexes to release the free enediyne in good
yield. Compared with stoichiometric oxidation, the
copper-catalyzed air oxidation offers the advantage that
smaller amounts of copper salts need to be separated
from the free enediyne product. In one example, a
solution of manganese enediyne complex [Cp(CO)2Mn]2-
[η2,η2-PhCtCC(CH2CH2CH2)dCCtCPh] (14) was gen-
erated in situ from reaction of [Cp(CO)2MntCPh]BCl4
(6) with 1,6-heptadiyne, CuBr, LiI, and EtNi-Pr2; air
was bubbled through the crude reaction solution to give
a 93% isolated yield of free enediyne 15. Similarly, air
oxidation of the crude reaction mixture from the prepa-
ration of [Cp(CO)2Mn]2[η2,η2-PhCtCC(CH2OCH2)dCCt
CPh] led to isolation of 2,3-(phenylethynyl)1,4-dihydro-
furan (36) in 95% yield (Scheme 10).
Photolysis of solutions of manganese enediyne com-
plexes with a sunlamp was followed by TLC. The
disappearance of a bright red spot due to the manganese
enediyne complex was accompanied by the appearance
of a strongly fluorescent spot due to the free enediyne.
At the end of photolysis, a fine brown precipitate that
had formed was removed by filtration. For small-scale
work involving less than 1 mmol of enediyne complex,
photolysis is the preferred method, as photolysis byprod-
ucts are the easiest to separate chromatographically.
However, this method suffers from scale-up difficulties
since dilute (<0.01 M) solutions are required and since
the buildup of suspended insoluble manganese-contain-
ing byproducts interferes with the photolysis.
Photolysis of the isolated enediyne complex 14 pro-
duced the free enediyne 15 in 70% yield. When the
enediyne complex 23 generated in situ from the low-
temperature reaction of [Cp(CO)2MntCTol]BCl4 (16)

Synthesis of Cyclic cis-Enediynes
Organometallics, Vol. 22, No. 19, 2003 3919
Sch em e 11
substituents on the propargylic center of the starting
diynes are tolerated well, and unsymmetric enediyne
complexes are readily prepared by suitable choice of the
diyne precursor. The yields of the enediyne products
depended upon the size of the ring system formed: five-
membered cyclic enediynes were formed in highest yield,
six-membered cyclic enediynes were formed in good
yields, and seven-membered cyclic enediynes were
formed in moderate yield. Bicyclic systems (37-40) have
also been formed via this process. However, all attempts
to cyclize eight-membered or larger systems failed,
resulting in uncharacterized decomposition products.
Ta ble 3. Syn th esis of En ed iyn es by Cu (II)
Oxid a tion of Ma n ga n ese En ed iyn e Com p lexes
Der ived fr om Cop p er -Ca ta lyzed Ad d ition of
Diyn es to Ma n ga n ese Ca r byn e Com p lexes
Su m m a r y
Compared with our initial synthesis of rhenium
enediyne complexes, this new one-pot manganese-based
synthesis of free enediynes offers the advantage of
economical manganese starting materials and ease of
release of the enediynes from their metal complex. A
drawback of the current synthetic procedure is the need
to use very temperature sensitive and functional group
intolerant manganese carbyne complexes as starting
materials. Further efforts to improve this route will
focus on finding suitable substitutes for the highly
electrophilic carbyne complexes.
Exp er im en ta l Section
Cp (CO)2Mn dC(Tol)CtCTol (17). 4-Ethynyltoluene (0.089
mL, 0.702 mmol), CuBr (10.7 mg, 0.075 mmol), LiI (7.8 mg,
0.058 mmol), and EtNi-Pr2 (0.135 mL, 0.780 mmol) in 4 mL of
tetrahydrofuran were added to a solution of [Cp(CO)2Mnt
CTol]BCl4 (16) (0.3372 g, 0.781 mmol) in CH2Cl2 (35 mL) at
-78 °C. The yellow solution quickly turned a dark red. After
30 min at -78 °C, solvents were evaporated under vacuum.
Column chromatography (silica, 10% ether/hexanes) gave dark
red-black crystals of 17 (203 mg, 73%). 1H NMR (250 MHz,
CD2Cl2): δ 7.93 (d, J ) 8.5 Hz, 2H, Tol), 7.48 (d, J ) 8.0 Hz,
2H, Tol), 7.24 (d, J ) 8.5 Hz, 2H, Tol), 7.25 (d, J ) 8.5 Hz, 2H,
Tol), 5.19 (s, 5H, Cp), 2.37 (s, Me), 2.34 (s, Me). 13C{1H} NMR
(125 MHz, CD2Cl2): δ 300.6 (MndC), 233.8 (CO), 152.5 (Cipso),
139.9 (CMe), 129.6 (CMe), 134.7 (Cipso), 130.7 (HCTol), 129.3
(HCTol), 128.5 (HCTol), 125.5 (HCTol), 121.5 (CtC), 104.7
(CtC), 93.27 (Cp), 21.1 (Me), 20.8 (Me). IR (hexanes): 1978,
a
b
For preparation of diynes, see Experimental Section. Con-
ditions: 0.42 equiv of diyne per carbyne, CuBr, LiI, EtNi-Pr2,
CH2Cl2, -78 °C. c After purification by column chromatography.
Cu (II) Oxid a tion Relea ses En ed iyn es fr om Ma n -
ga n ese Com p lexes. Stoichiometric oxidation of man-
ganese enediyne complexes with CuCl2‚2H2O occurs
rapidly and releases the enediyne in good yield (Table
3). The chief advantage of this method is the speed of
the oxidation; its disadvantage is the use of large
quantities of copper salts that need to be removed in
the purification of the free enediynes. For example, a
solution of manganese enediyne complex [Cp(CO)2Mn]2-
[η2,η2-PhCtCC(CH2CH2OCH2)dCCtCPh] (41) gener-
ated in situ from the low-temperature reaction of
[Cp(CO)2MntCPh]BCl4 (6) with HCtCCH2CH2OCH2-
CCtCH, CuBr, LiI, and EtNi-Pr2 was oxidized with
CuCl2 to give an 82% yield of free enediyne 42 (Scheme
11). Similar yields of enediynes were obtained either
from photolysis, copper-catalyzed air oxidation, or sto-
ichiometric Cu(II) oxidation of enediyne complexes.
Scop e of En ed iyn e Syn th esis. This new procedure
involving copper-catalyzed addition of diynes to man-
ganese carbyne complexes followed by release of the
enediyne from the intermediate manganese enediyne
complexes has a broad scope. The procedure is highly
tolerant of most functional groups, including alkenes,
ethers, esters, and ketones (Tables 1-3). However, the
amine-containing substrates, tripropargylamine and
benzyl dipropargylamine, failed to undergo cyclization
and instead generated intractable material. Simple
1922 cm-1
.
[Cp (CO)2Mn ]2[η2,η2-TolCtCC(CH 2OCH 2)dCCtCTol]
(19). A solution of dipropargyl ether (0.026 mL, 0.252 mmol),
CuBr (8.8 mg, 0.061 mmol), LiI (9.0 mg, 0.067 mmol), and
EtNi-Pr2 (0.104 mL, 0.601 mmol) in 3 mL of tetrahydrofuran
was added to a solution of [Cp(CO)2MntCTol]BCl4 (0.2592 g,
0.600 mmol) in CH2Cl2 (50 mL) at -78 °C. After 30 min at
-78 °C, solvents were evaporated under vacuum. Column
chromatography (silica, 20-50% ether/hexanes) gave 19 (63
mg, 38%) as a bright red powder. 1H NMR (500 MHz, CD2Cl2,
-30 °C): δ 7.07 (d, J ) 7.5 Hz, 4H, HTol), 6.93 (d, J ) 7.5 Hz,
4H, HTol), 5.46 (d, J ) 9 Hz, 2H, CHH), 5.04 (d, J ) 9 Hz, 2H,
CHH), 4.80 (s, Cp), 2.20 (s, Me). 13C{1H} NMR (125 MHz,
CDCl3, -30 °C): δ 232.2 (CO), 231.2 (CO), 137.0 (CMe), 133.3
(CdC), 132.3 (HCTol), 131.8 (Cipso), 127.9 (HCTol), 88.3 (CtC),
84.9 (Cp), 78.9 (CH2), 63.2 (CtC), 20.04 (Me). IR (CH2Cl2):
1973, 1907 cm-1. MS (ESI): m/z calcd for C36H28O555Mn2 (M+)
650.1, found 650.1.
[Cp(CO)2Mn ]2[η2,η2-P h CtCC(CH2C(CO2Me)2CH2)dCCt
CP h ] (21). A solution of dimethyl dipropargylmalonate (183
mg, 0.88 mmol), CuBr (60 mg, 0.42 mmol), LiI (58 mg, 0.43
mmol), and EtNi-Pr2 (365 µL, 2.11 mmol) in 10 mL of
tetrahydrofuran was added to a solution of [Cp(CO)2MntCPh]-
BCl4 (6) (881 mg, 2.11 mmol) in CH2Cl2 (170 mL) at -78 °C.

3920 Organometallics, Vol. 22, No. 19, 2003
Casey et al.
After 30 min at -78 °C, solvents were evaporated under
vacuum, and the residue was extracted with CH2Cl2 (20 mL)
and diluted with 200 mL of hexanes. The solution was filtered
and evaporated under a nitrogen stream to give 21 (0.549 g,
85%) as a bright red powder. A sample for NMR experiments
was further purified by column chromatography (silica, 20-
50% ether/hexanes). X-ray quality crystals were grown by
(CO)2MntCPh]BCl4 (6) (558 mg, 1.33 mmol) in CH2Cl2 (90 mL)
at -78 °C. The red solution was stirred at room temperature
for several hours and poured into an equal volume of THF.
Air was slowly bubbled through the solution for 90 min,
resulting in a color change from deep red to brown. One
strongly fluorescent spot was observed by TLC analysis.
Solvents were evaporated under vacuum, and the residue was
purified by flash chromatography (silica, 10% ethyl acetate/
hexanes) to give 15 (139 mg, 93%) as a pale yellow solid.
1
layering ether onto a concentrated CH2Cl2 solution of 21. H
NMR (300 MHz, CD2Cl2): δ 7.21-7.17 (m, 4H, HPh), 7.10-
7.05 (m, 6H, HPh), 4.83 (s, Cp), 3.86 (s, CO2Me), 4.0-3.6 (broad,
CH2). 13C{1H} NMR (125 MHz, CDCl3, -30 °C): δ 232.3 (CO),
231.3 (CO), 171.0 (CO2Me), 134.3 (CdC), 132.5 (HCPh), 129.9
(Cipso), 127.0 (HCPh), 126.2 (HCPh), 87.5 (CtC), 85.1 (Cp), 67.8
(CtC), 57.1 (C(CO2Me)2), 52.7 (CO2Me), 44.9 (Me). IR (CH2-
P h CtCC(CH2OCH2)dCCtCP h (36). A solution of dipro-
pargyl ether (54 µL, 0.524 mmol), CuBr (30 mg, 0.209 mmol),
LiI (29 mg, 0.22 mmol), and EtNi-Pr2 (227 µL, 1.31 mmol) in
3 mL of THF was added to a solution of [Cp(CO)2MntCPh]-
BCl4 (6) (548 mg, 1.31 mmol) in CH2Cl2 (100 mL) at -78 °C.
The red solution was stirred at room temperature for 1 h and
poured into an equal volume of THF (90 mL). Air was slowly
bubbled through the solution for 1.5 h, resulting in a color
change from deep red to brown. One strongly fluorescent spot
was observed by TLC analysis. The combined solvents were
removed by rotary evaporation. The residue was dissolved in
ethyl acetate, and the solution was filtered and evaporated
again. The residue was purified by flash chromatography
(silica, 25% ethyl acetate/hexanes) to give 36 (135.2 mg, 95%)
Cl2): 1972, 1907, 1734 cm-1. MS (ESI): m/z calcd for C39H30
-
O855Mn2 (M+) 736.07, found 736.0.
TolCtCC[(C6H4)CH2C(CO2Me)2CH2]dCCtCTol (24). A
solution of diyne 22 (118 mg, 0.415 mmol), CuBr (12 mg, 0.084
mmol), LiI (17 mg, 0.12 mmol), and EtNi-Pr2 (170 µL, 1.00
mmol) in 3 mL of tetrahydrofuran was added to a solution of
[Cp(CO)2MntCTol]BCl4 (16) (472 mg, 1.09 mmol) in CH2Cl2
(70 mL) at -78 °C. The solution was stirred overnight at room
temperature and poured into 20% ether/hexanes (200 mL) and
photolyzed with a 150 W sunlamp for several hours. One
strongly fluorescent spot was observed by TLC analysis. The
combined solvents were evaporated, and the residue was
purified by flash chromatography (silica, 10% ethyl acetate/
hexanes) to give 24 (130 mg, 67%) as a pale yellow oil. 1H NMR
(500 MHz, CDCl3): δ 7.66 (d, J ) 7.5 Hz, 1H, HAr), 7.46 (d,
J ) 8.0 Hz, 4H, HTol), 7.37 (td, J ) 7.3, 2.0 Hz, 1H, HAr), 7.32-
7.26 (m, 2H, HAr), 7.17 (d, J ) 8.0 Hz, 2H, HTol), 7.16 (d, J )
8.0 Hz, 2H, HTol), 3.81 (s, CO2Me), 3.34 (s, CH2), 2.88 (s, CH2),
2.39 (s, Me), 2.38 (s, Me). 13C NMR (125 MHz, CDCl3): δ 170.8
(s, CO2Me), 138.6 (s, CAr), 138.2 (s, CAr), 136.0 (s, CAr), 131.4
1
as an off-white solid. H NMR (500 MHz, CDCl3): δ 7.53 (br
s, 4H, Ph), 7.37 (br s, 6H, Ph), 4.85 (s, 4H, CH2). 13C NMR
1
(125 MHz, CDCl3): δ 132.5 (d, J CH ) 160 Hz, CPh), 129.6 (dt,
2
1
1J CH ) 161 Hz, J CH ) 8 Hz, CPh), 129.1 (d, J CH ) 160 Hz,
CPh), 126.4 (s, CdC), 123.3 (s, Cipso), 99.8 (s, CtCAr), 82.0 (s,
1
CtCAr), 78.2 (t, J CH ) 151 Hz, CH2). HRMS(EI): m/z calcd
for C20H14O (M+) 278.1045, found 270.1036.
P h CtCC(CH2CH 2OCH2)dCCtCP h (42). A solution of
(3-butynyl) propynyl ether (79 µL, 81% solution in toluene,
0.978 g mL-1, 0.579 mmol), CuBr (23 mg, 0.161 mmol), LiI
(21 mg, 0.15 mmol), and EtNi-Pr2 (239 µL, 1.38 mmol) in 3
mL of THF was added to a solution of [Cp(CO)2MntCPh]BCl4
(6) (577 mg, 1.38 mmol) in CH2Cl2 (110 mL) at -78 °C. The
resulting red solution was stirred at room temperature for
several hours. The solution was poured into an equal volume
of THF (150 mL), and an ethanol solution (20 mL) of CuCl2‚
2H2O (530 mg, 3.12 mmol) was added. A color change from
deep red to brown occurred, and one strongly fluorescent spot
was observed by TLC analysis. The combined solvents were
evaporated under vacuum, and the residue was extracted into
ethyl acetate. The solution was filtered and evaporated. The
residue was purified by flash chromatography (silica, 25%
ethyl acetate/hexanes) to give 42 (135.3 mg, 82%) as a slightly
yellow solid. 1H NMR (300 MHz, CDCl3): δ 7.55-7.45 (m, 4H,
Ph), 7.35-7.30 (m, 6H, Ph), 4.34 (t, J ) 3 Hz, OCH2CdC), 3.87
(t, J ) 6 Hz, OCH2CH2), 2.49 (tt, J ) 6, 3 Hz, OCH2CH2). 13C
NMR (125 MHz, CDCl3): δ 132.3 (d, 1J CH ) 160 Hz, CPh), 129.1
1
1
(d, J CH ) 160 Hz, CTol), 131.4 (d, J CH ) 160 Hz, CTol), 130.2
1
1
(d, J CH ) 140 Hz, CAr), 130.0 (s, CAr), 129.1 (d J CH ) 153 Hz,
1
1
C
Tol), 129.0 (d J CH ) 153 Hz, CTol), 128.4 (dd, J CH ) 158 Hz,
2J CH ) 7 Hz, CAr), 128.2 (dd, 1J CH ) 160 Hz, 2J CH ) 8 Hz, CAr),
1
2
127.2 (dd, J CH ) 159 Hz, J CH ) 8 Hz, CAr), 126.0 (s, CdC),
2
2
120.3 (t, J CH ) 8 Hz, Cipso), 120.1 (t, J CH ) 8 Hz, Cipso), 97.5
(s, CtCTol), 97.1 (s, CtCTol), 90.7 (s, CtCTol), 88.7 (s,
CtCTol), 66.8 (s, C(CO2Me)2), 52.8 (q, 1J CH ) 147 Hz, CO2Me),
1
1
37.3 (t J CH ) 131 Hz, CH2), 37.0 (t J CH ) 134 Hz, CH2), 21.4
1
(q, J CH ) 126 Hz, Me). IR (CH2Cl2): 1735 cm-1. HRMS(ESI):
m/z calcd for C33H28O4Na (M+) 511.1886; found, 511.1907.
P h CtCC(CH2CH2CH2)dCCtCP h (15).14 Addition of 1,6-
heptadiyne (55.2 mg, 0.60 mmol), CuI (57 mg, 0.30 mmol, 25
mol % per CtCH), LiI (40 mg, 0.30 mmol), and 500 mg of EtNi-
Pr2 in 2 mL of THF to an orange solution of [Cp(CO)2Mnt
CPh]BCl4 (6) (687 mg, 1.64 mmol) in 5 mL of THF at -35 °C
produced a dark red color immediately. The crude product was
washed through a 3 cm silica pad with 2:1 hexane/diethyl ether
to give [Cp(CO)2Mn]2[η2,η2-PhCtCC(CH2CH2CH2)dCCtCPh]
(14) as a red solid (318 mg, 0.51 mmol, 85%). Photolysis with
a medium-pressure Hg lamp (254 nm maximum) in 100 mL
of THF/CH3CN under air gave 15 as a colorless solid (96.0 mg,
70% yield from 14, yield from 1,6-heptadiyne: 60%). 1H NMR
1
(d, J CH ) 162 Hz, CPh), 126.0 (s, CdC), 124.5 (s, CdC), 123.9
(s, Cipso), 123.7 (s, Cipso), 97.1 (s, CtCPh), 95.5 (s, CtCPh), 89.4
1
(s, CtCPh), 86.7 (s, CtCPh), 68.5 (t, J CH ) 146 Hz, CH2),
1
1
64.6 (t, J CH ) 137 Hz, CH2), 30.0 (t, J CH ) 130 Hz, CH2).
HRMS(EI): m/z calcd for C21H16O (M+) 284.1201; found,
284.1200.
3
(500 MHz, CD2Cl2): δ 2.03 (t, J ) 8 Hz, CH2CH2CH2), 2.70
3
Ack n ow led gm en t. Financial support from the Na-
tional Science Foundation is gratefully acknowledged.
Grants from NSF (CHE-9629688) for the purchase of
the NMR spectrometers and a diffractometer (CHE-
9709005) are acknowledged.
(t, J ) 8 Hz, CH2CdC), 7.30-7.40 (m, aromatic CH), 7.46-
7.56 (m, aromatic CH). 13C NMR (125 MHz, CD2Cl2): δ 23.5
1
1
(t, J CH ) 131 Hz, CH2CH2CH2), 37.4 (t, J CH ) 132 Hz, CH2-
CH2CH2), 86.6 (s, CtCAr), 96.8 (t, 3J CH ) 5 Hz, CtCAr), 123.8
(t, 3J CH ) 7 Hz, aromatic), 128.8 (d, 1J CH ) 162 Hz, aromatic),
1
3
128.8 (dd, J CH ) 163 Hz, J CH ) 7 Hz, aromatic), 130.7 (m,
CdC), 131.9 (dt, 1J CH ) 160 Hz, 3J CH ) 6 Hz, aromatic). HRMS-
(EI): m/z calcd for C21H16 (M+) 268.1252, found 268.1239.
P h CtCC(CH2CH2CH2)dCCtCP h (15). A solution of 1,6-
heptadiyne (64 µL, 0.56 mmol), CuBr (18 mg, 0.123 mmol),
LiI (16 mg, 0.12 mmol), and EtNi-Pr2 (230 µL, 1.33 mmol) in
3 mL of tetrahydrofuran was added to a solution of [Cp-
Su p p or tin g In for m a tion Ava ila ble: Preparation of com-
pounds, spectroscopic data, and X-ray crystal structures. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OM0303799