Stoichiometric and Catalytic (η 5 -Cyclopentadienyl)cobalt-Mediated Cycloisomerizations of Ene-Yne-Ene Type Allyl Propargyl Ethers

Article abstract of DOI:10.1055/s-0039-1690727

The complexes CpCoL ₂ (Cp = C ₅ H ₅; L = CO or CH ₂ =CH ₂) mediate the cycloisomerizations of α,δ,ω-enynenes containing allylic ether linkages to 3-(oxacyclopentyl or cycloalkyl)furans via the interme

Full text of DOI:10.1055/s-0039-1690727

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–R
paper
A
en
C.-A. Chang et al.
Paper
Synthesis
Stoichiometric and Catalytic (η5-Cyclopentadienyl)cobalt-Mediated
Cycloisomerizations of Ene-Yne-Ene Type Allyl Propargyl Ethers
Chu-An Chang
O
Stefan Gürtzgen
Erik P. Johnson
K. Peter C. Vollhardt*
0
0
0
0-0
0
0
2-5
8
9
1-
1
3
2
0
CpCo
65%
O
CpCo(CH2=CH2)2
(1 equiv), 0 °C
Δ
Department of Chemistry, University of California at Berkeley,
Berkeley, California 94720-1460, USA
kpcv@berkeley.edu
Quantitative
O
O
O
CpCo(CO)2
(0.2 equiv), Δ, hν
83%
O
Received: 05.09.2019
Accepted after revision: 07.10.2019
Published online: 28.10.2019
prevalent (and relevant within the context of this report) is
the oxidative coupling pathway that engenders conjugated
dienes, as depicted in its simplest form in Scheme 1. Here,
the metal first enables the reorganization of the two types
of ligands in A to generate B, which, in the majority of cases,
undergoes rapid -hydride elimination to C, followed by re-
ductive elimination to liberate butadiene D. Much rarer is
the interception of B by another alkene component, as in E,
followed by insertion to metalla-4-cycloheptene F, its -hy-
dride elimination to G, and final reductive elimination from
G to give hexadiene H. The paucity of this pathway can be
traced to the intervention of competing trajectories, domi-
nant among which are the alternative to intermolecular B →
E, namely intramolecular B → C,1 or reductive elimination
from F to create the [2+2+2] cycloaddition products.2 In or-
der to minimize the former and enhance the likelihood of
the incorporation of the second alkene unit, a number of
studies have employed all-intramolecular options with
mixed results (Scheme 2).
DOI: 10.1055/s-0039-1690727; Art ID: ss-2019-m0511-op
Abstract The complexes CpCoL2 (Cp = C5H5; L = CO or CH2=CH2) medi-
ate the cycloisomerizations of ,,-enynenes containing allylic ether
linkages to 3-(oxacyclopentyl or cycloalkyl)furans via the intermediacy
of isolable CpCo-η4-dienes. A suggested mechanism comprises initial
complexation of the triple bond and one of the double bonds, then oxi-
dative coupling to a cobalt-2-cyclopentene, terminal double bond in-
sertion to assemble a cobalta-4-cycloheptene, -hydride elimination,
and reductive elimination to furnish a CpCo-η4-diene. When possible,
the cascade continues through cobalt-mediated hydride shifts and dis-
sociation of the aromatic furan ring. The outcome of a deuterium label-
ing experiment supports this hypothesis. The reaction exhibits variable
stereoselectivity with a preference for the trans-product (or, when ar-
rested, its syn-Me CpCo-η4-diene precursor), but is completely regiose-
lective in cases in which the two alkyne substituents are differentiated
electronically by the presence or absence of an embedded oxygen. Re-
gioselectivity is also attained by steric discrimination or blocking one of
the two possible -hydride elimination pathways. When furan forma-
tion is obviated by such regiocontrol, the sequence terminates in a sta-
ble CpCo-η4-diene complex. The conversion of the cyclohexane-fused
substrate methylidene-2-[5-(2-propenyloxy)-3-pentynyl]cyclohexane
into mainly 1-[(1R*,3aS*,7aS*)-7a-methyloctahydroinden-1-yl]-1-eth-
anone demonstrates the potential utility of the method in complex syn-
thesis.
−M
H
M
Reductive
elimination
C
D
Key words enynes, -hydride elimination, cobalt, cycloisomerization,
furans
β-Hydride
elimination
M
M
M
M
M
Insertion
Oxidative
coupling
Transition-metal-catalyzed hydroalkenylative coupling
reactions of alkenes with alkynes, particularly their intra-
molecular variants (‘enyne cycloisomerizations’) constitute
powerful additions to the arsenal of the synthetic chemist.1
Depending on substrates, the choice of the metal, and con-
ditions, various products may arise, including conjugated
and skipped dienes or their reduced analogues, as well as
cyclobutane and cyclopropane derivatives. Among the
mechanisms proposed for these conversions, particularly
H
A
B
E
−M
M
H
M
Reductive
elimination
β-Hydride
elimination
H
F
G
H
Scheme 1 Generic oxidative coupling mechanism of the hydroalkenyl-
ation of alkynes to give 1,3-butadienes and 1,3-hexadienes
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–R
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
C.-A. Chang et al.
Paper
Synthesis
Thus, titanacycloheptane 2, made from 1, converted 1
catalytically into a mixture of hydrocarbons, in which 3 was
believed to be the major component, although no spectral
data were given.3 A series of investigations aimed primarily
at effecting [2+2+2] cycloadditions of enynenes and di-
enynes to assemble the corresponding cyclohexenes de-
scribe the occasional generation of cycloisomerization
products according to Scheme 1 (in addition to other struc-
tures formed by competing mechanisms),1e their relative
preponderance depending on substrates and reaction con-
ditions. For example, a cationic Rh catalyst rearranged 4 to
5 and 6 via presumed intermediate I, the route to 6 obviated
by changing the tether between the double bonds or the tri-
ple bond substituent.4 The postulate of I is unusual, in as
much as it features insertion of the second double bond
into the usually less favored alkylmetal side of the initial
metallacyclopentene. In a report of thirteen examples of
the [2+2+2] cycloaddition of enynenes bearing oxa- and
azatethers mediated by cationic Rh, 7 was unique in its
transformation into the diene stereoisomers (E)- and (Z)-8,
presumably emerging via -hydride elimination from J.5
Similarly, [Me5CpRuCl(1,5-cyclooctadiene)] accomplished
Rothwell, 2003
Sato, 2012
E
E
E
E
H
[Ti(OC6H3Ph2-2,6)2Cl2]
(0.4 equiv), Na-Hg (0.9
equiv Na), C6H6, r.t., 12 h
E
E
E
E
[Me5CpRuCl(1,5-
cyclooctadiene)]
(0.05 equiv),
1 (excess),
100 °C
H
H
C
Ti(OAr)2
PhMe, 50 °C, 1 h
67%
+
H
3 (tentative)
1
2
E
E
E
E
12, 36%
Shibata, 2008
11, E = CO2Me
13, 33%
TolBINAP (0.1 equiv),
13 via β-hydride elimination from
Ph
Ph
[Rh(1,5-cyclooctadiene) ]BF
Ph
2
4
E
(0.1 equiv), H2, CH2Cl2, then
O
E
H
4, DCE, 40 °C, 6 h
+
O
O
6 via β-hydride elimination from
RuLn
L:
Ph
MLn
H
E
H
O
E
I:
5, 51%
4
6, 30%
Kudinov, 2015; Perekalin, 2017
Kudinov: [(C4Et4)Rh(p-xylene)PF6
Tanaka, 2008
[Rh(1,5-cyclooctadiene)2]BF4
(0.05 equiv), (R)-(+)-2,2'-
bis(diphenylphosphino)-
5,5',6,6',7,7',8,8'-octahydro-
1,1'-binaphthyl (0.05 equiv),
H2, CH2Cl2, 30 min, then 7,
DCE, 80 °C, 3 h
(0.02 equiv),
CHCl3-MeCN (20:1), 60 °C, 24 h;
Perekalin: CoBr2 (0.2 equiv),
Zn (0.2 equiv), ZnI2 (0.2 equiv),
1,2-bis(diphenylphoshino)ethane
(0.2 equiv), THF, r.t.
Ts
N
O
TsN
TsN
O
97 or 96%
70%
O
via β-hydride elimination from
N
O
Ts
O
H
15
14
J:
RhL2
7
8, Z/E = 3.3:1
15 via β-hydride elimination from
O
TsN
H
Sato, 2011
M:
MLn
H
TsN
Ts
N
TsN
[Me5CpRuCl(1,5-cyclooctadiene)]
(0.05 equiv), PhMe, 60 °C, 1 h
Sato, 2016
E
E
E
93%
[Rh(1,5-cyclooctadiene)2]BF4
(0.1 equiv), (R)-BINAP (0.1
equiv), H2, DCE, r.t., 30 min,
then 18, DCE, 40 °C, 3 h
E
via β-hydride elimination from
N
TsN
Ts
TsN
H
N
S
K:
RuLn
10
9
97%
N
TsN
H
S
O
O
via β-hydride elimination from
16, E = CO2Me
17
E
E
H
RhLn
N:
N
S
H
O
Scheme 2 Pertinent intramolecular cycloisomerizations of enynenes and dienynes, including imine analogue 16, to furnish various 1,2- or 1,4-dienes
according to the general mechanism in Scheme 1
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–R

C
C.-A. Chang et al.
Paper
Synthesis
mostly [2+2+2] cyclizations of enynenes, with minor excep-
tions, one of which is depicted in Scheme 2, namely the al-
most quantitative evolution of 10 from 9 via metallacycle
K.1m,6 The same catalyst effects analogous reorganizations
for thirteen enynallenes, and only in the case of 11 was the
cycloisomerization endpoint 13 isolated, in addition to
equal quantities of the cycloaddition framework 12.7 Per-
haps not unexpectedly, in light of the observations made
with 9, 14 converted exclusively into 15 in the presence of a
cationic cyclobutadiene Rh complex.8 Remarkable, however,
is the dependence of the product selectivity from 14 (and
the corresponding ether analogues) using Co (in the form of
a mixture of CoBr2, Zn, and ZnI2) on the nature of added
phosphine ligands. Hence, as shown, 1,2-bis(diphenyl-
phoshino)ethane led only to 15, whereas Ph3P created ex-
clusively the [2+2+2] cycloadducts.9 The latter were com-
pletely avoided in the cationic Rh-enabled cycloisomeriza-
tion of seven imines of the type 16, giving only products of
the type 17.10
As the preceding summary illustrates, there is poor
control over the outcome of the intramolecular transition-
metal-catalyzed stitching of two double bonds with a C≡C
bond. In this paper, we expand the range of current knowl-
edge by adding CpCoL2 (Cp = C5H5; L = CO or CH2=CH2) to
the number of catalysts that can be employed, leading to
complementary insights.11
The requisite starting materials, shown in Figure 1, were
either known (19,12 20,12 22,13 27,12 28,14 and 3015) or made
by established strategies [see experimental section and
Supporting Information (SI)].
O
Our experiments commenced with enynene 18, the
bishomologue of 1. Exposure to CpCo(CO)2 (0.3 equiv) in
boiling m-xylene under irradiation for six hours led to the
complete disappearance of starting material and formation
of a complex mixture of products (see experimental sec-
tion). Varying the reaction conditions [CpCo(CO)2 (1 equiv),
boiling decalin; CpCo(CH2=CH2)2, with and without irradia-
tion from –50 to 80 °C; CpCo(CH2=CH2)2, PPh3 (1 equiv)
with and without irradiation from 0 to 50 °C; CpCo(PPh3)2,16
60 °C] and following the progress of the disappearance of
18 by GC, MS, TLC, and NMR suggested the occurrence of
double bond isomerization,1a,b,11,17 dimerization, trimeriza-
tion, and alkyne cleavage to a biscarbyne18 (see experimen-
tal section). While the presence of the desired bishomo-
logue of 3 in the mixture could not be ruled out, this possi-
bility was not investigated further. Rather, and exploiting
the long-known accelerating effect of allylic and propargyl-
ic heteroatoms in transition-metal-catalyzed cyclizations
(which also appear to be of benefit in the relevant examples
of Scheme 2),19 we turned to 19 as the next substrate.
Gratifyingly, exposure of 19 to catalytic CpCo(CO)2 in
boiling and irradiated PhMe effected clean isomerization to
furan 36 in the form of only one isolated stereoisomer
(Scheme 3). However, the presence of another isomer in the
crude reaction mixture was suggested by low intensity
(2.5%) 1H NMR signals at  = 1.90 (s) and 0.75 (d, J = 6.7 Hz).
A control experiment verified the necessity of the cata-
lyst in this process, as 19 is untouched under these condi-
tions without it. The gross structural features of 36 were
O
O
O
18
19
27
28
O
O
O
O
O
O
O
O
O
O
MeO2C
O
O
CO2Me
20
29
O
O
21
30
O
O
O
O
SiMe3
22
31
O
O
23
32
O
O
O
O
24
25
26
33
34
35
O
O
1
corroborated by its NMR data. Thus, the H NMR spectrum
O
revealed two singlets in the aromatic region [ = 7.18 (1 H),
7.14 (1 H)], as well as two methyl resonances, one a singlet
at  = 1.96, the other a doublet at  = 1.05 (J = 6.6 Hz). Ab-
sorptions attributable to the four protons on the oxygen-
bearing carbons appeared as ABM spin systems between  =
4.5 and 3.5, and the remaining tetrahydrofuran peaks
showed up in the alkyl region. The 13C NMR spectrum ex-
hibited the expected ten peaks, occurring in three groups,
O
O
O
Figure 1 Starting materials used in this study
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–R

D
C.-A. Chang et al.
Paper
Synthesis
assignable to the furan ( = 140.0, 138.6, 124.7, 119.8), tet-
rahydrofuran ( = 75.1, 73.7, 43.0, 40.3), and methyl car-
bons ( = 16.0, 8.48), respectively.
Unfortunately, the proton couplings were undiagnostic
for the assignment of the stereochemistry in 36,20 and an
NOE experiment proved inconclusive for this purpose. Con-
sequently, and also because of the profound reorganization
occurring during the genesis of 36, X-ray structural support
for the formulated structure was sought. Since the sub-
stance was an oil, a sequence was devised that transformed
it into a crystalline derivative without compromising the
configuration around the stereocenters (Scheme 3). A mild
protocol of choice presented itself in the initial ozonolysis-
oxidation of the furan ring to the carboxylic acid, namely 37
(or its cis-isomer),21 which, if not crystalline, could then be
further altered to such a derivative. Confidence in the stere-
oretentive nature of this oxidation was derived from the
finding that the two stereoisomers of 2-methylcyclopen-
tanecarboxylic acid do not epimerize in strong acid (3 N
HCl).22 Moreover, the half-life for epimerization of the cor-
responding methyl esters with strong base at 35 °C (NaOMe,
MeOH) was estimated to be 8–29 hours, with a ratio of
trans/cis = 9.4 at equilibrium.23 In the event, ozonolysis and
oxidative workup of 36 with careful control of the pH pro-
ceeded uneventfully (Scheme 3). Acid 37 emerged as an oil
that could not be crystallized and was therefore reacted
with 2-bromo-1-(4-bromophenyl)ethan-1-one, again un-
der pH control,24 to afford 38. Crystallization from hot hex-
ane supplied material suitable for X-ray analysis (Figure
2).25 The stereochemistry is unequivocally trans in 38 and
thus, by inference, in 36.
Figure 2 Structure of 38 in the crystal
double bond insertion to assemble Q, -hydride elimination
to R, and reductive elimination to diene complex 39. Finally,
cobalt-mediated syn-hydride shifts1a,b,11,17 and departure of
the metal from the aromatized ring26 finishes the sequence.
As the color in Scheme 4 indicates, the process involves an
extensive redistribution of hybridization states. While the
stereochemistry of O (with the complexed alkenyl hydro-
gen positioned syn to the Cp) and of P (with the complexed
alkenyl hydrogen positioned anti to the Cp and the tertiary
hydrogen) are written such as to lead to that observed in
36, there are complementary alternatives that accomplish
the same. Thus, most steps are likely reversible,1,27 the
mechanism is expected to involve rapidly inverting triplet
16-electron CpCo intermediates (‘dual state mecha-
nism’),27h,l and the complexed diene unit in 39 may be sub-
ject to double inversion by an envelope flip,28 adding a
plethora of additional mechanistic options. Therefore, in
the absence of a computational treatment, Scheme 4 is
meant to be only suggestive. Finally, while the pronounced
stereoselectivity towards 36 invites mechanistic specula-
tion about its origins, the validity of such an effort is negat-
ed by the much less selective outcomes of additional exam-
ples (vide infra).
A mechanism for the catalytic reorganization of 19 to
36, patterned after the general outline of Scheme 1, is de-
picted in Scheme 4. It features initial complexation of the
triple bond and one of the double bonds, as in O, then oxi-
dative coupling to the cobalt-2-cyclopentene P, terminal
1. O3, CH2Cl2, MeOH,
–78 °C
O
O
O
2. H2O2 (excess),
NaOH, H2O, 0 °C,1.5 h
3. HCl, H2O, pH 2
H
O
O
CpCo(CO)2 (0.18 equiv),
H
O
Cp
H
Cp
Co
"CpCo"
PhMe, Δ, hν, 12 h
Cp Co
19
Co
H
70%
64%
O
H
O
H
O
O
36
19
O
P
Q
1. H2O, pH 9.5
O
O
O
O
O
O
2. 2-Bromo-1-(4-
bromophenyl)ethan-1-
one, EtOH, 80 °C, 2 h
O
O
O
O
HO
Cp(H)Co
51%
O
O
CpCo
Br
37
38
36
39
R
Scheme 3 Cycloisomerization of 19 to 36 and derivatization to crystal-
line 38
Scheme 4 Mechanism of the cycloisomerization of 19 to 36
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–R

E
C.-A. Chang et al.
Paper
Synthesis
Notwithstanding the preceding disclaimers, two addi-
tional experiments supported aspects of Scheme 4. The
first addressed the topological veracity of the -hydride
transfer process. For this purpose, 19-d2 (97% label incorpo-
ration by 1H NMR spectroscopy) was prepared from 3-
chloro-1-propene-2-d29 and 2-butyne-1,4-diol and subject-
ed to the isomerization conditions (Scheme 5). The 1H NMR
spectrum of 19-d2, when compared to that of 1912 exhibited
the expected (near) disappearance of the absorption at  =
5.87 due to the internal alkenyl hydrogens and the corre-
sponding simplification of the splitting patterns of their
neighbors (for a comparison of the spectra, see SI). In con-
sonance with Scheme 4, the resulting 36-d2 (94% label in-
corporation by 1H NMR spectroscopy) showed the presence
of the label only in the 4-methyl and 4-position of the tetra-
hydrofuranyl substituent (for numbering, see Scheme 5), as
indicated by the metamorphosis of the original methyl dou-
blet into a broad singlet, the (near) disappearance of the
multiplet at  = 2.28 arising from H4, and the simplification
of its three neighboring signals by removal of one coupling
each.
identified the complexed diene carbons at  = 100.0 and
95.8 (internal), and at 59.8 and 23.2 (terminal), in addition
to exhibiting lines for the remaining carbons with the ex-
pected chemical shifts. In further support of the proposed
mechanism in Scheme 4, 39 converted cleanly into 36 at
80–100 °C in PhMe (1H NMR).
To investigate the scope of this cycloisomerization, sev-
eral variations of the enynene substrates were scrutinized,
including adding alkyl substituents to the double bonds, in-
corporating electron-withdrawing units, changing the rela-
tive positioning of the triple bond, and replacing one of the
oxygens by carbon. First on the list was dimethylated 20, in
which the substituents obviate -hydride elimination,
therefore perhaps allowing the detection of competing
pathways of reactivity. Indeed, under standard cyclization
conditions and employing 20 and CpCo(CO)2 in equimolar
quantities, the air-sensitive diene complexes 40 and 41
were formed in a 1:1 ratio and 54% yield (Scheme 6). With
CpCo(CH2=CH2)2 at 0 °C and starting materials in the stoi-
chiometric ratio of 2:1, the products emerged in 80% yield
and a 1:3 ratio.
The second experiment was aimed at arresting the
progress of the isomerization at the stage of the diene com-
plex 39 by exposing 19 to the reactive CpCo source Cp-
Co(CH2=CH2)2 at 0 °C, inspired by a related strategy in the
[2+2+2] cycloaddition of ,,-enediynes.17a Gratifyingly,
this treatment produced 39 in 70% yield. Its structure was
strongly supported by the NMR spectra, in which the at-
tached metal serves to cause characteristic structurally and
stereochemically diagnostic shieldings.17,30 Specifically,
apart from the 1H NMR signals for the eight methylene hy-
drogens next to oxygen between  = 4.7 and 3.3, the two
terminal complexed diene protons appeared at  = 1.86
(outer or E-position) and 0.28 (inner or Z-position). The lo-
cation of the methyl group as syn to CpCo was divulged by
its relatively deshielded peak at  = 1.10, while the neigh-
boring tertiary anti-H exhibited a correspondingly relative-
ly shielded multiplet at  = 0.55. The 13C NMR spectrum
O
O
CpCo(CO)2
(1 equiv), PhMe,
Δ, hν, 6 h
CoCp
O
O
Me
O
O
syn or anti
to Co
20 (1 equiv)
40 (anti-CH3), 27%
41 (syn-CH3), 27%
Scheme 6 [2+2+2] Cocycloaddition of 20 to furnish 40 and 41
Their structural assignments rested on mass spectral
and NMR data. Most diagnostic with respect to stereochem-
istry were the positions of the angular methyl hydrogen sig-
1
nals in the H NMR spectra, characteristically shielded for
40 ( = 0.79) relative to those of 41 ( = 1.43). In addition,
accidentally isochronous peaks were observed for the re-
spective three terminal 2-propenyl hydrogens ( = 4.87–
4.97) and distinct AB quartets for one of the methylene
fragments of the tetrahydrofuran ring ( = 3.48 and 3.47, re-
spectively), the others overlapping to give rise to multiplets.
The corresponding pairs of doublets for the CH2 moiety of
the complexed cyclohexadiene ring occurred at  = 1.89 and
1.21, and at 1.03 and 0.06, respectively. The 13C NMR spec-
trum of only 41 was recorded and it exhibited all of the ex-
pected lines, several of which were assignable. For example,
there were two sets of three singlets due to the terminal
alkene carbons around 142 and 111 ppm, respectively; the
complexed internal diene carbons resonated at  = 90.7 and
85.5, close to the Cp signal at  = 81.0; ten lines from  =
75.8–66.0 included all carbons attached to oxygen and the
1. NaH (2 equiv),
DMSO, r.t., 3 h
D
2.
Cl
OH
(2 equiv), DMSO,
D
r.t., 18 h
O
O
D
38%
19-d2
HO
5
D
O
D
O
CpCo(CO)2 (0.33 equiv),
4
PhMe, Δ, hν, 6 h
3
2
74%
36-d2
Scheme 5 Fate of the deuterium label in the cycloisomerization of 19-
d2 to 36-d2
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–R

F
C.-A. Chang et al.
Paper
Synthesis
complexed terminal diene carbons; the peak at  = 51.0
arose from the tertiary ring carbon, those at  = 32.4 and
29.2 from the cyclohexadiene CH2 and the methyl group,
and a broad singlet at  = 19.5 was assigned to the three ac-
cidentally isochronous alkenyl methyls.
Mechanistically, while it is tempting to assume that the
steric bulk around the neopentylic hydrogen renders the
endocyclic -hydride elimination process from the te-
tramethyl species analogous to P and Q (Scheme 4) relative-
ly noncompetitive,1,27c,32 it is difficult to rationalize the ab-
sence of its exocyclic counterpart involving the hydrogens
of one of the methyl groups, leading to the skipped diene
topology (an option deliberately omitted from Scheme 1,
because it was not recorded in the chemistry described in
this paper). Moreover, such an endocyclic -hydride elimi-
nation is observed for 23 (vide infra). We therefore prefer,
as above for 40 and 41, initial oxidative alkyne coupling as
the pathway to 42.
A plausible mechanistic rationale for the emergence of
40 and 41 from 20 is via the interception of the dimethyl
analogue of P in Scheme 4 (possibly in equilibrium with the
dimethyl analogue of Q, both frustrated with respect to -
hydride elimination) by another molecule of 20, thus enter-
ing the [2+2+2] cocycloaddition pathway to the product. Al-
ternatively, and perhaps more likely, the increased steric
encumbrance of the double bond (relative to 19) may slow
its participation in metallacycle of type P formation to favor
initial oxidative coupling of the triple bonds of two mole-
cules of 20 to the corresponding cobaltacyclopentadiene,
followed by incorporation of the alkene moiety to give 40
and 41.31
In view of the results with 20 and 21, it was of interest
to test 22 and 23, in which the level of impedance to cy-
cloisomerization had been attenuated such as to leave one
of the termini of 19 intact. Indeed, as shown in Schemes 8
and 9, these substrates mimicked the behavior of 19.
Next to be examined was 21, in which the -hydride
elimination pathway was enabled and the terminal methyl
groups served to test the tolerance of the cyclization to ste-
ric hindrance. From a practical standpoint, the latter would
also simplify the NMR spectral analysis of eventual prod-
ucts. In the event, the fate of 21, when confronted with Cp-
Co(CO)2, equaled that of 20, except that only diastereomer
42 was generated (Scheme 7).
O
CpCo
O
CpCo(CH2=CH2)2
(1 equiv), PhMe,
0 °C, 1 d
PhMe, 80 °C,
1 d
quant.
44
65%
O
O
O
CpCo(CO)2
(0.2 equiv), PhMe,
Δ, hν, 10 h
78%
O
O
O
CpCo(CO)2
(0.43 equiv),
CoCp
O
PhMe, Δ, hν, 6 h
O
46%
22
43
H
O
O
Scheme 8 Cycloisomerization of 22 to 43 directly and via 44
The structures of compounds 43 and 44 were readily as-
certained by the similarity of their NMR spectra to those of
36 and 39, respectively, including the changes expected by
the presence of the extra methyl group (see experimental
section and SI). The furans isolated from the cyclization of
21
42
Scheme 7 [2+2+2] Cocycloaddition of 21 to furnish 42
1
1
As hoped, the H NMR spectrum of 42 was largely re-
23 were inseparable. Nevertheless and fortunately, the H
solved to render first order patterns, facilitating the assign-
ment of the stereochemistry of the tertiary hydrogen of the
complexed cyclohexadiene ring as located syn to the metal
[ = 3.52 (dd, J = 7.1, 7.1 Hz)]. Its neighboring nuclei are
clearly differentiated with respect to their relative position:
 = 1.10 (CH3-syn), 0.57 (CH3-anti); 2.68 (CHH-syn), 2.24
(CHH-anti); remote tetrahydrofuran-CH2: 3.82 (CHH-syn),
3.25 (CHH-anti). The 13C NMR spectrum gave rise to the
complexed cyclohexadiene absorptions at  = 90.1 and 87.4
(internal) and 66.5 and 65.4 (terminal; pinpointed by
DEPT), the two remaining six-membered-ring carbons res-
onating at  = 61.1 (tertiary) and 28.8 (quaternary), the two
methyl carbons at  = 31.6 (syn to CpCo) and 27.2 (anti), re-
spectively.
NMR spectrum was completely resolved, allowing the rec-
ognition of the two isomers 45 and 46, present in the ratio
55:45, and assigned as the cis- and trans-isomers, respec-
tively. The regiochemistry of the alkyl groups was indicated
by the relatively deshielded positions and multiplicity of
the isopropyl methine resonances at  = 2.67 (sept) and
2.69 (sept), respectively, clearly pinpointing their attach-
ment to the furan ring. Conversely, the unique C4-methyl
groups (for numbering see Scheme 9) gave rise to doublet
absorptions at  = 0.74 and 1.07, respectively, confirming
their connectivity to the tetrahydrofuran substructure.
The designation of the stereochemistry of 46 as trans
rested on the similarity of the 1H NMR data for its tetrahy-
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–R

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C.-A. Chang et al.
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Synthesis
als was noted, no desired products were formed. A possible
explanation for this failure is that the insertion of the ter-
minal double bond into the saturated alkylcobalt side of the
initial cobaltacyclopentene intermediate is prohibitively
slow.16
5
5
O
O
O
CpCo(CO)2
(0.8 equiv), PhMe,
4
4
2
2
Δ, hν, 10 h
3
3
+
23%
An important aspect of this chemistry to be probed was
the necessity of the diallyl ether array for its success,
prompting the interrogation of monoallyl ethers 32–35.
Puzzlingly, when 32 was treated with CpCo(CO)2 in boiling
toluene, the consequence was a complex mixture, contain-
ing several complexes, as highlighted by their orange-red
color on TLC analysis. In an effort to access any free ligands,
the crude product was treated with CuCl2·2H2O,30 prompt-
ing decomposition. The issue was resolved by carrying out a
low temperature experiment with CpCo(CH2=CH2)2, which
provided the two complexes 47 and 48 in high yield, in a ra-
O
H
O
O
O
CoCp
via S:
55:45
H
O
23
45
46
Scheme 9 Cycloisomerization of 23 to 45 and 46
Table 1 Selection of Comparative 1H NMR data (ppm) for 45, 46, and
36a
Complex H2 ()
H3 ()
H4 () H5 ()
C4-CH3 ()
1
tio of 2:1 (Scheme 10). While inseparable, their H NMR
spectrum exhibited resolved features for each isomer, as-
45
46
36
4.07, 3.50
3.26
2.77
2.72
2.52
2.26
2.28
4.05, 3.78
0.74
1.07
1.05
signable by comparison with the corresponding data for 39
4.18, 3.56
4.14, 3.60
4.10, 3.44
4.08, 3.43
and 44 (see experimental section and SI). Similarly, the 13
C
NMR spectrum showed the expected doubling of relevant
absorptions. Attempted oxidative demetalation led to po-
lymerization, likely a reflection of the sensitivity of the free
ligand.33 Interestingly, although not unexpectedly,1,27c,32 -
hydride elimination from the desymmetrized version of Q,
namely T (Scheme 10), occurs away from the oxygen to
construct only the bis(alkylidenecyclopentane) regioiso-
mers shown in Scheme 10, evidently incapable of entering
the hydrogen shift manifold that leads to the emergence of
aromatic furans.
a For numbering, see Scheme 9.
drofuran ring with those of 36 and their divergence from
those of 45 (Table 1).
The outcome of the cycloisomerization depicted in
Scheme 9 provides some mechanistic insight. First, the near
equimolar formation of cis- and trans-isomers shows that
the reaction is not generally stereoselective, as implied ear-
lier by the (possibly) exclusive formation of the trans com-
pound 36 from 19. Therefore, cobalt-4-cycloheptene inter-
mediates of the type Q (Scheme 4) may be accessible in
both stereoisomeric forms (see also the conversion of 1 into
the cis complex 2 in Scheme 2). Such lack of stereoselectivi-
ty will repeat itself in other examples (vide infra). Second,
the regioselective formation of 45 and 46 signals that -hy-
dride elimination from the dimethyl analogue of Q, namely
S (Scheme 9), favors the more substituted trajectory, the re-
sult of stereoelectronic effects.1,27c,32
O
O
syn or anti
to Co
CpCo(CH2=CH2)2
(1 equiv), PhMe,
0 °C, 1 d
O
H
CpCo
via T:
CoCp
H
One notes that, as in the case of 21, -hydride elimina-
tion to the terminal methyl substituent in 23 was not ob-
served. Therefore, an attempt was made to enforce such a
pathway by exploring the reactivity of 24 (Figure 1), in
which the endocyclic pathway is blocked, but its exo coun-
terpart remains enabled. Unfortunately, its reaction with
CpCo(CO)2 under the standard conditions led to a complex
mixture that was not further characterized.
At this stage, it was thought instructive to activate (po-
tentially) the double bonds in 18 and 19 with electron-
withdrawing groups, as in the esters 25–29. Lamentably,
this exercise turned into a fiasco, as the starting materials,
on attempted cycloisomerization, polymerized. This meth-
odology could also not be extended to include enynenes
such as 30 and 31, in which the triple bond locus was ter-
minal. While complete consumption of the starting materi-
32
47 (syn-CH3), 57%
48 (anti-CH3), 29%
Scheme 10 Cycloisomerization of 32 to 47 and 48
The preceding conjecture was tested with the derivative
33, in which the pathway traversed by 32 is blocked. In-
deed, standard cyclization of this substrate led to furan 49
in good yield (Scheme 11), revealing spectral data that com-
pared well with those of its relatives 36, 43, 45, and 46.
On the other hand, simple chain extension of 32, as in
34, reproduced the trajectory depicted in Scheme 10, ex-
cept that the resulting diene complexes were stable to the
higher temperature conditions of their generation from
CpCo(CO)2 in boiling PhMe.
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–R

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C.-A. Chang et al.
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Synthesis
O
O
O
O
CpCo(CO)2
(0.4 equiv), PhMe,
Δ, hν, 6 h
CpCo(CO)2
(0.8 equiv),
PhMe, Δ, hν, 5 h
0.91 (53)
0.75 (54)
1
59%
7a
5
H
33
49
35
53 (cis,trans), 47%
54 (cis,cis), 11%
Scheme 11 Cycloisomerization of 33 to 49
Scheme 13 Cycloisomerization of 35 to 53 and 54 and the 1H NMR
chemical shifts of the methyl groups in the products
Here, the main consequence of switching to
CpCo(CH2=CH2)2 at 0 °C was an increased ratio of syn to anti
complexes 50 and 51 (Scheme 12). The structural assign-
ments of these compounds followed those made for their
analogues 39, 44, 47, and 48. Further chemical corrobora-
tion of their identities as diastereomers was obtained by
oxidative demetalation, which provided a single diene 52
(Scheme 12).
and determination of their ratio of 4:1, the latter confirmed
by 1H NMR spectroscopy.
The NMR spectra of 53 and 54 were sufficiently re-
solved to allow assignments of all signals but for the six
methylene groups (see experimental section and SI), a find-
ing that, unfortunately, did not reveal stereochemical iden-
tity. Two considerations led us to adopt a bias toward the
formulation of the hydrindane fusion as being cis. The first
was mechanistic and based on molecular models, which
showed that the approach U of the methylidenecyclohex-
ane double bond to the metal that leads to the cis configura-
tion is sterically considerably more favorable than the alter-
native V (Figure 3).
O
O
syn or anti
to Co
CpCo(CO)2 (1 equiv),
PhMe, Δ, hν, 6 h
or (1H NMR)
CpCo(CH2=CH2)2
(1 equiv), PhMe-d8,
0 °C, 1 h
CpCo
H
H
O
O
Co
H
H
Co
34
50 (syn-CH3), 46%
51 (anti-CH3), 27%
or (1H NMR)
50 (syn-CH3), 75%
51 (anti-CH3), 15%
CuCl2·2H2O
(3.5. equiv),
DME, r.t., 15 min
U
V
Figure 3 The two approaches of the methylidenecyclohexane double
bond to cobalt: U leads to the eventual cis-hydrindane fusion, V to the
trans-alternative
53%
O
The second rested on the relatively greater similarities
of the NMR chemical shifts of the atoms at the fusion of 53
52
1
and 54 – H NMR:  (CH3) = 0.91 and 0.75, Htert = 1.94 and
2.11; 13C NMR:  (CH3) = 23.4 and 24.0, fusion = 42.3/47.5
Scheme 12 Cycloisomerization of 34 to 50 and 51, followed by de-
metalation to 52
and 43.6/45.2 – when compared to the dissimilarities at the
1
point of attachment of the furyl substituent H NMR:  =
A final substrate to be inspected was the annulated
enynene 35, in which substitution at the alkyl end was ex-
pected to ensure furan formation, and the presence of a ste-
reocenter raised the issue of potential diastereoselectivity.
Cycloisomerization of 35 in the presence of CpCo(CO)2 un-
der the usual conditions led to a mixture of only two of the
four possible furylhydrindanes 53 and 54, which could not
be separated preparatively by standard column chromatog-
raphy (Scheme 13). Segregation occurred on GC, however,
allowing for the recording of the individual mass spectra
2.51 and 2.93; 13C NMR:  = 45.5 and 39.2.
Turning to the choice of the disposition of the furyl
group in the major isomer 53 as trans to the adjacent meth-
yl, it was indicated by the larger chemical shift of the angu-
lar methyl group compared to that in 54 (Scheme 13). This
assignment finds precedence in the reported larger chemi-
cal shifts (Δ = 0.2–0.3) for related trans- versus cis-isomers
of a series of cis-fused 7a-methyl-5-oxooctahydroindene-1-
carboxylic acid derivatives (Scheme 13 and vide infra).34
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–R

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C.-A. Chang et al.
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Synthesis
The tenuousness of these arguments prompted an effort
to convert the mixture of 53 and 54 into known compounds
(Scheme 14). In this vein, ozonolysis, using a modified liter-
ature procedure,35 furnished a 4:1 mixture of the carboxylic
acids 55 and 56,36 exhibiting the expected IR and NMR
spectral fingerprints, in particular the projected changes
when going from starting materials to products. Moreover,
and strengthening the preceding argument for the relative
stereochemistry at C1, the major isomer exhibited  (CH3) =
1.19, its minor kin  (CH3) = 0.93. The corresponding 5-
oxoacids show  (CH3) = 1.45 and 1.14, respectively.34 Treat-
ment of 55 and 56 with MeLi, TMSCl, and aqueous HCl37 in
sequence supplied a 4:1 mixture of the known38 diastereo-
meric methyl ketones 57 and 58, whose stereochemistry
pletely regioselective in cases in which the starting alkyne
is unsymmetrical: When one side of the enynene is blocked
with respect to -hydride elimination, the other side is cho-
sen (Scheme 8); when one side features terminal substitu-
tion, the intermediate cobaltacycloheptene favors a hydride
shift from the more substituted site (Scheme 9); when only
one side contains an electron-withdrawing oxygen, -hy-
dride elimination is directed away from it (Scheme 12), un-
less this option is blocked (Scheme 11). When both double
bonds are blocked or excessively encumbered by substitu-
tion, the cycloisomerization option is outcompeted by
[2+2+2] cycloaddition to produce CpCo-η4-cyclohexadiene
products derived from the coupling of two substrate
molecules (Schemes 6 and 7). The synthetic potential of the
method is highlighted by the conversion of methylidene-
2-[5-(2-propenyloxy)-3-pentynyl]cyclohexane into 1-
[(1R*,3aS*,7aS*)-7a-methyloctahydroinden-1-yl]-1-ethanone
as the major isomer.
1
was corroborated by comparison of the H NMR chemical
shifts of the angular CH3 groups [ (CH3) = 1.25 and 0.87]
with those in the literature [ (CH3) = 1.27 and 0.88].38 Note
that the ratio of diastereomers remained constant through-
out the sequence from furans to methyl ketones, making
epimerization highly unlikely, thus lending credibility to
the assigned structures for 53 and 54.
Unless otherwise noted, all materials were obtained from commercial
suppliers and used without further purification. Solvents and/or reac-
tants were degassed by purging with dry N2 or argon for 3 min. All
reactions with water-sensitive materials were carried out under dry
N2. Melting points were obtained with a Büchi melting point appara-
tus and are uncorrected. THF, DME, and Et2O were distilled directly
from Na/benzophenone ketyl prior to use. CH2Cl2, DMSO, pyridine,
and Et3N were distilled from CaH2 and stored over 3Å molecular
sieves. PhMe was extracted sequentially with concd H2SO4 at 0 °C (4 ×
100 mL per L of solvent), H2O (2 × 100 mL), and sat aq NaHCO3, then
predried via azeotropic distillation, and stored over 3Å molecular
sieves. MeOH was distilled from Mg under N2. t-BuOH was recrystal-
lized until its melting point exceeded 24.5 °C. TLC was performed on
commercial silica gel (Analtech, GHLF 250 micron, 10 × 2.5 cm glass,
containing CaSO4 and fluorescent indicator) plates, and visualizations
were accomplished with anisaldehyde-H2SO4, phosphomolybdic acid-
Ce4+-H2SO4 spray, or UV illumination. GC was performed on either a
Shimadzu Mini-2 instrument, interfaced with a Model TPM 2R tem-
perature programmer and Hewlett-Packard Model 3390A Integrator,
or a Hewlett-Packard Model 5880A integrating chromatograph, both
equipped with 12 m OV-101 fused silica capillary columns. 1H NMR
spectra were recorded on any of these superconducting FT instru-
ments: Varian EM-390, UCB-250, BVX-300, Bruker AM-400, or AM-
500 MHz, respectively. They are reported on the  scale in ppm, with
chemical shifts referenced to the residual signal of the solvent, and
are tabulated in the order: multiplicity (standard abbreviations), cou-
pling constant(s), number of protons, and, if possible, assignment. As-
signments (see SI) were made using the COSY pulse sequence or by
decoupling experiments. 1H-Decoupled 13C NMR spectra were ob-
tained on either the BVX-300 or Bruker AM-400 spectrometers.
Chemical shifts are referenced to the residual signal of the solvent.
Unless trivial, assignments were made routinely with the assistance
of the DEPT 135° pulse sequence and/or by comparison with the
spectra of similar compounds. 31P NMR (relative to the chemical shift
of 85% H3PO4) data are the result of proton decoupling. IR spectra
were measured on PerkinElmer Model 681 or 137 instruments, refer-
enced to polystyrene (1601 cm–1); liquids were analyzed neat on NaCl
plates and solids in KBr pellets. Low-resolution mass spectra are given
as m/z values and were obtained at 70 eV with Atlas MS-12, Hewlett-
Packard 5970A, or Finnigan 4000 mass spectrometers. Peak intensity
1. O3, CH2Cl2,
MeOH (3:1), –78 °C
2. H5IO6 (3 equiv),
H2O, H2SO4,
O
CO2H
acetone, r.t., 6 h
76%
H
H
53 + 54, 4:1
55 + 56, 4:1
1. MeLi (2.8. equiv),
THF, 0 °C, 2 h
2. TMSCl (4 equiv), 0 °C,
5 min, r.t., 1 h
O
O
3. HCl (1 N), r.t., 4.5 h
+
42%
H
H
57
58
4:1
Scheme 14 Sequential conversion of 53 and 54 via 55 and 56 into 57
and 58
To conclude, we have shown that the complexes CpCoL2
(Cp = C5H5; L = CO or CH2=CH2) facilitate the cycloisomeri-
zations of ,,-enynenes containing allylic ether linkages,
thus complementing related chemistry in the literature.
Uniquely, the reaction cascades can be arrested at the stage
of the intermediate CpCo-η4-diene complexes derived from
-hydride elimination of the postulated cobalta-4-cyclo-
heptenes (Schemes 8, 10, and 12). Similarly, when possible,
these complexes can proceed by hydride shifts to furan
products, thus rendering the process catalytic (Schemes 3,
8, 9, 11, and 13). The transformation is not stereoselective,
but exhibits a preference for the trans-furan product
(Schemes 3, 9, and 13) or, when arrested, the syn-Me CpCo-η4-
diene complex (Schemes 10 and 12). It is, however, com-
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–R

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C.-A. Chang et al.
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Synthesis
is expressed as percent total ion current normalized with respect to
the base peak. High-resolution mass spectra were determined with a
Consolidated 12-110B mass spectrometer. Elemental analyses were
performed by the Microanalytical Laboratory operated by the College
of Chemistry, University of California at Berkeley.
mL). Column chromatography on silica gel, eluting with Et2O/hexane
(3:50), furnished 23 as a colorless, moderately air-sensitive oil; yield:
530 mg (69%).
IR (film): 2970, 2920, 2850, 1445, 1375, 1350, 1120, 1070, 1020, 990,
925 cm–1
.
1H NMR (300 MHz, CDCl3):  = 5.88 (ddt, J = 17.3, 11.3, 5.7 Hz, 1 H),
5.31 (m, 1 H), 5.28 (br d, J = 17.3 Hz, 1 H), 5.19 (br d, J = 10.8 Hz, 1 H),
4.18 (t, J = 2.6 Hz, 2 H), 4.15 (t, J = 2.7 Hz, 2 H), 4.05 (m, 2 H), 4.02 (m,
2 H), 1.73 (s, 3 H), 1.68 (s, 3 H).
13C NMR (75 MHz, CDCl3):  = 138.2, 133.9, 120.2, 117.8, 82.6, 82.0,
70.5, 66.0, 57.4, 57.1, 25.8, 18.0.
1,13-Tetradecadien-7-yne (18)
To anhydrous liquid NH3 (freshly distilled from Na; 150 mL) were add-
ed Na (1.20 g, 52 mmol) and a few crystals of anhyd Fe(NO3)3. The
mixture was stirred for 1 h at –33 °C, cooled to –78 °C, and then treat-
ed with a solution of 1-octen-7-yne39 (2.80 g, 25.9 mmol) in Et2O (150
mL) for 30 min. To this solution was added slowly 6-bromo-1-hexene
(5.00 g, 30.6 mmol) in Et2O (150 mL) and the resulting reaction mix-
ture stirred at r.t. until the solvent had evaporated. The residual mate-
rial was taken up in Et2O, washed with H2O (3 × 50 mL), the solvent
evaporated, and the remaining oil distilled through a Kugelrohr to
give 18 as a colorless liquid; yield: 3.00 g (61%); bp 80–85 °C/5 Torr.
Anal. Calcd for C12H18O2: C, 74.19; H, 9.34. Found: C, 73.83; H, 9.37.
1-[(E)-2-Methyl-2-butenyloxy]-4-(2-methyl-2-propenyloxy)-2-bu-
tyne (24)
The general etherification procedure was executed using 4-(2-meth-
yl-2-propenyloxy)-2-butyn-1-ol42 (2.300 g, 16.41 mmol), KOH (4.33
g, 77 mmol), DMSO (50 mL), and 1-bromo-2-methyl-2-butene43
(2.446 g, 16.41 mmol). Column chromatography on silica gel, eluting
with Et2O/hexane (1:20), afforded 24 as a colorless oil; yield: 2.231 g
(65%).
IR (film): 3100, 2950, 2850, 1820, 1640, 1460, 1440, 1330, 1000, 910
cm–1
.
1H NMR (300 MHz, CDCl3):  = 5.78 (ddt, J = 16.5, 9.0, 7.5 Hz, 2 H), 4.99
(dd, J = 16.5, 1.5 Hz, 2 H), 4.85 (dd, J = 9.0, 1.5 Hz, 2 H), 2.35 (m, 4 H),
2.03 (m, 4 H), 1.48 (m, 8 H).
IR (film): 3080, 2970, 2940, 2910, 2840, 1650, 1445, 1370, 1345,
13C NMR (75 MHz, CDCl3):  = 138.7, 114.5, 80.1, 33.4, 28.7, 28.2, 18.7.
13C NMR (75 MHz, PhMe-d8):  = 138.9, 114.7, 80.4, 33.8, 29.1, 28.6,
1200, 1140, 1115, 1070, 895, 835 cm–1
.
1H NMR (250 MHz, CDCl3):  = 5.49 (m, 1 H), 4.95 (br s, 1 H), 4.89 (br s,
1 H), 4.14 (t, J = 1.7 Hz, 2 H), 4.09 (t, J = 1.7 Hz, 2 H), 3.93 (s, 2 H), 3.89
(s, 2 H), 1.71 (br s, 3 H), 1.61 (s, 3 H), 1.58 (br d, J = 8.3 Hz, 3 H).
13C NMR (75 MHz, CDCl3):  = 141.4, 132.1, 123.6, 112.8, 82.5, 82.0,
75.8, 73.5, 57.2, 56.7, 19.5, 13.6, 13.2.
19.1.
MS (EI, 70 eV): m/z (%) = 190 ([M+], 2), 147 (10), 133 (18), 119 (19),
107 (54), 93 (74), 79 (100), 67 (67).
Anal. Calcd for C14H22: C, 88.42; H, 11.57. Found: C, 88.21; H, 11.49.
General Etherification Procedure for the Synthesis of 21, 23, and
2440
1-[4-(2-Propenyloxy)-2-butynyl] Propenoate (25)
To a stirred solution of 4-(2-propenyloxy)-2-butyn-1-ol41 (1.000 g,
7.927 mmol) and Et3N (2.2 mL, 1.6 g, 16 mmol) in CH2Cl2 (20 mL) at
0 °C was added neat propenoyl chloride (1.086 g, 12.00 mmol) via sy-
ringe over 5 min with the formation of a brown precipitate. The mix-
ture was stirred for 12 h at r.t., treated with sat. aq NaOAc (10 mL), the
layers separated, and the aqueous phase extracted with CH2Cl2 (20
mL). The combined organic layers were dried (MgSO4), filtered, con-
centrated in vacuo, and subjected to column chromatography on silica
gel, eluting with Et2O/hexane (1:9), to sequester 25 as a faintly yellow,
unstable oil; yield: 670 mg (47%).
To a vigorously stirred solution of the unsaturated alcohol in DMSO
contained in a 125 mL conical flask was added KOH in one portion.
The brown slurry was stirred for 45 min at r.t. and the neat halide
dripped in at 0–5 °C over 15–30 min. The mixture was stirred for 30
min at 0 °C, then 1–3 h at 40–45 °C. The brown slurry was poured into
ice-H2O (200 mL) and extracted with hexane (3 × 85 mL). The com-
bined organic phases were washed with H2O (100 mL), dried (MgSO4),
filtered, and concentrated in vacuo to yield the crude product.
1,4-Bis[(3-methyl-2-butenyl)oxy]but-2-yne (21)
IR (film): 3070, 2980, 2940, 2850, 1735, 1635, 1435, 1410, 1355,
1265, 1180, 1140, 1080, 1050, 980, 930, 810 cm–1
.
The general etherification procedure was employed using 2-butyne-
1,4-diol (491 mg, 5.70 mmol), KOH (1.45 g, 25.8 mmol), DMSO (10
mL), and 1-bromo-3-methyl-2-butene (1.000 g, 6.710 mmol). Ex-
tractions were performed with pentane (3 × 10 mL). Column chroma-
tography on silica gel, eluting with Et2O/hexane (1:4), rendered 21 as
an air-sensitive oil; yield: 398 mg (31%).
1H NMR (250 MHz, CDCl3):  = 6.43 (dd, J = 17.3, 1.4 Hz, 1 H), 6.11 (dd,
J = 17.3, 10.4 Hz, 1 H), 5.86 (ddt, J = 17.2, 10.4, 5.8 Hz, 1 H), 5.85 (dd,
J = 10.4, 1.4 Hz, 1 H), 5.27 (ddt, J = 17.2, 1.6, 1.5 Hz, 1 H), 5.22 (ddt, J =
10.4, 1.6, 1.5 Hz, 1 H), 4.78 (t, J = 1.8 Hz, 2 H), 4.17 (t, J = 1.8 Hz, 2 H),
4.02 (ddd, J = 5.8, 1.3, 1.3 Hz, 2 H).
13C NMR (75 MHz, CDCl3):  = 165.2, 133.7, 131.7, 127.6, 117.9, 82.8,
80.2, 70.7, 57.3, 52.3.
IR (film): 2970, 2920, 2850, 1670, 1445, 1375, 1350, 1110, 1070, 930
cm–1
.
1H NMR (300 MHz, CDCl3):  = 5.31 (tsept, J = 7.0, 1.4 Hz, 2 H), 4.15 (s,
4 H), 4.02 (d, J = 7.0 Hz, 4 H), 1.73 (br s, 6 H), 1.68 (br s, 6 H).
13C NMR (75 MHz, CDCl3):  = 138.2, 120.2, 82.4, 66.0, 57.1, 25.8, 18.0.
1-[4-(2-Propenyloxy)-2-butynyl] (E)-2-Butenoate (26)
To a solution of 4-(2-propenyloxy)-2-butyn-1-ol41 (700 mg, 5.55
mmol) and anhyd pyridine (8 mL) in CH2Cl2 (30 mL) at r.t. was intro-
duced trans-2-butenoyl chloride (0.70 mL, 76 mg, 73 mmol) via sy-
ringe in one portion. The mixture was stirred for 12 h, H2O (20 mL)
added, the layers separated, and the aqueous phase extracted with
hexane (15 mL). The combined organic fractions were extracted suc-
cessively with H2O (15 mL) and sat. aq CuSO4 (15 mL), filtered, dried
1-(3-Methyl-2-butenyloxy)-4-(2-propenyloxy)-2-butyne (23)
The general etherification procedure was implemented using 4-(2-
propenyloxy)-2-butyn-1-ol41 (500 mg, 3.96 mmol), KOH (890 mg,
15.9 mmol), DMSO (10 mL), and 4-bromo-2-methyl-2-butene (671
mg, 4.50 mmol). Extractions were performed with pentane (3 × 10
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–R

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C.-A. Chang et al.
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Synthesis
(MgSO4), and concentrated in vacuo to give a yellow syrup that was
subjected to Kugelrohr distillation to supply 26 as a faintly yellow, un-
stable oil; yield: 873 mg (81%); bp 120–129 °C/15 Torr.
1H NMR (250 MHz, CDCl3):  = 5.88 (ddt, J = 17.2, 10.3, 5.7 Hz, 1 H),
5.71 (ABX4m, 2 H), 5.24 (ddt, J = 17.2, 1.6, 1.6 Hz, 1 H), 5.15 (ddt, J =
10.3, 1.4, 1.3 Hz, 1 H), 4.10 (s, 2 H), 4.10 (br d, J = 5.3 Hz, 2 H), 4.05 (br
d, J = 5.4 Hz, 2 H), 3.95 (dt, J = 5.6, 1.4 Hz, 2 H), 0.15 (s, 9 H).
IR (film): 3060, 2920, 2830, 1715, 1640, 1435, 1355, 1295, 1235,
1150, 1125, 1070, 1010, 980, 955, 920 cm–1
.
13C NMR (62.5 MHz, CDCl3):  = 134.5, 130.3, 128.4, 117.2, 101.3, 91.4,
71.2, 65.6, 64.9, 57.8, –0.19.
1H NMR (300 MHz, CDCl3):  = 6.95 (dq, J = 15.6, 6.9 Hz, 1 H), 5.80 (m,
2 H), 5.21 (dt, J = 17.2, 1.7 Hz, 1 H), 5.12 (dt, J = 10.4, 1.3 Hz, 1 H), 4.69
(t, J = 1.8 Hz, 2 H), 4.10 (t, J = 1.8 Hz, 2 H), 3.96 (ddd, J = 5.8, 1.3, 1.3 Hz,
2 H), 1.81 (dd, J = 6.9, 1.7 Hz, 3 H).
Synthesis of 32–35 from 3-(2-Propynyloxy)-1-propene; General
Procedure
13C NMR (75 MHz, CDCl3):  = 165.3, 145.7, 133.6, 121.6, 117.6, 82.4,
80.3, 70.4, 57.1, 51.7, 17.9.
A 100 mL round-bottomed flask fitted with a septum was charged
with NaH (1.05 equiv), rendered oil-free by washing with anhyd Et2O
(3 × 10 mL), and DMSO (30 mL). The resulting slurry was heated to
65–75 °C in an oil bath with stirring until the NaH had dissolved, giv-
ing a green-grey solution. After cooling to r.t., 3-(2-propynyloxy)-1-
propene was added via syringe over 5 min, the mixture stirred for 1 h,
and the bromoalkene introduced via syringe over 10 min with suffi-
cient cooling to maintain a reaction temperature below 30 °C. After
6–12 h, the mixture was diluted with H2O (60 mL) and extracted with
hexane (3 × 20 mL). The combined organic phases were washed with
H2O (50 mL), dried (MgSO4), filtered, and concentrated in vacuo to
supply the crude product.
Dimethyl trans,trans-Tetradeca-2,12-dien-7-ynedioate (29)
5-Decynedial
To a suspension of powdered PCC (1.80 g, 8.35 mmol) and NaOAc (150
mg, 1.82 mmol) in CH2Cl2 was added 5-decyn-1,10-diol30d (400 mg,
2.35 mmol) at r.t. After stirring for 1.5 h, the solvent was evaporated
and the dark residue chromatographed on silica gel, eluting with Et2O,
to lead to 5-decynedial as a colorless oil; yield: 250 mg (64%).
IR (film): 2950, 2740, 1730, 1395, 1340, 1135, 1080, 940 cm–1
.
1H NMR (250 MHz, CDCl3):  = 9.77 (t, J = 1.2 Hz, 2 H), 2.53 (dt, J = 7.2,
1.2 Hz, 4 H), 2.19 (t, J = 5 Hz, 4 H), 1.78 (m, 4 H).
MS (EI, 70 eV): m/z (%) = 166 ([M+], 0.5), 123 (23), 110 (30), 95 (44), 78
8-(2-Propenyloxy)-1-octen-6-yne (32)
The preceding general procedure was employed using NaH (669 mg,
27.86 mmol), 3-(2-propynyloxy)-1-propene (2.500 g. 26.01 mmol),
and 5-bromo-1-pentene (4.024 g. 27.00 mmol). Kugelrohr distillation
presented 32 as a colorless oil; yield: 2.795 g (65%); bp 94–104 °C/18
Torr.
(91), 55 (100).
29
IR (film): 3080, 2980, 2940, 2860, 1645, 1445, 1355, 1135, 1090, 990,
5-Decynedial (400 mg, 2.41 mmol) and methoxycarbonylmethylene-
triphenylphosphorane (2.23 g, 6.67 mmol) were stirred in benzene
(15 mL) at r.t. for 3 h and at 80 °C for 8 h. The solvent was evaporated
and the residue chromatographed on neutral alumina (activity), elut-
ing with Et2O/pentane (3:2), to deliver 29 as a colorless oil; yield: 194
mg (29%).
910 cm–1
.
1H NMR (300 MHz, CDCl3):  = 5.88 (ddt, J = 17.2, 11.4, 5.7 Hz, 1 H),
5.76 (ddt, J = 16.9, 13.4, 6.7 Hz, 1 H), 5.27 (dd, J = 17.2, 1.5 Hz, 1 H),
5.18 (dd, J = 10.4, 1.5 Hz, 1 H), 5.01 (dd, J = 18.5, 1.4 Hz, 1 H), 4.96 (dd,
J = 10.1, 1.0 Hz, 1 H), 4.11 (t, J = 2.0 Hz, 2 H), 4.02 (dd, J = 4.7, 1.0 Hz, 2
H), 2.22 (tt, J = 7.0, 1.9 Hz, 2 H), 2.12 (dt, J = 7.4, 7.3 Hz, 2 H), 1.59 (tt,
J = 7.3, 7.3 Hz, 2 H).
IR (film): 2942, 1726, 1658, 1432, 1325, 1272, 1200, 1150, 1095,
1043, 979, 913, 856 cm–1
.
13C NMR (75 MHz, CDCl3):  = 137.7, 134.1, 117.6, 115.1, 86.6, 76.1,
70.4, 57.7, 32.8, 27.7, 18.2.
1H NMR (250 MHz, CDCl3):  = 6.93 (dt, J = 15.6, 7.0 Hz, 2 H), 5.81 (dt,
J = 15.6, 1.5 Hz, 2 H), 3.70 (s, 6 H), 2.28 (m, 4 H), 2.15 (t, J = 7.0 Hz, 4
H), 1.61 (m, 4 H).
Anal. Calcd for C11H16O: C, 80.44; H, 9.82. Found: C, 80.30; H, 9.94.
13C NMR (62.5 MHz, CDCl3):  = 167.8, 149.4, 122.3, 80.8, 52.2, 32.0,
28.1, 19.0.
2-Methyl-8-(2-propenyloxy)-1-octen-6-yne (33)
The preceding general procedure was employed using NaH (264 mg,
11.0 mmol), 3-(2-propynyloxy)-1-propene (1.153 g, 12.00 mmol),
and 5-bromo-2-methyl-1-pentene (1.600 g, 9.812 mmol). The crude
product was chromatographed on silica gel, eluting with Et2O/hexane
(1:20), to give 33 as a colorless oil; yield: 627 mg (36%).
MS (EI, 70 eV): m/z (%) = 278 ([M+], 2), 277 (5), 263 (15), 187 (37), 159
(70), 91 (84), 81 (100).
HRMS (EI, 70 eV): m/z [M+ – 1] calcd for C16H21O4: 277.1439; found:
277.1434.
IR (film): 3070, 2930, 2850, 1650, 1450, 1370, 1350, 1135, 1085,
cis-1-(2-Propenyloxy)-4-(3-trimethylsilyl-2-propynyloxy)-2-
butene (31)
1020, 995, 925, 890 cm–1
.
1H NMR (300 MHz, CDCl3):  = 5.89 (ddt, J = 16.2, 10.4, 5.8 Hz, 1 H),
5.27 (dd, J = 17.3, 1.5 Hz, 1 H), 5.18 (d, J = 10.4 Hz, 1 H), 4.71 (br s, 1 H),
4.67 (br s, 1 H), 4.12 (t, J = 2.0 Hz, 2 H), 4.03 (br dt, J = 5.8, 1.1 Hz, 2 H),
2.20 (tt, J = 7.2, 1.9 Hz, 2 H), 2.09 (br t, J = 7.4 Hz, 2 H), 1.70 (s, 3 H),
1.64 (tt, J = 7.5, 7.0 Hz, 2 H).
13C NMR (75 MHz, CDCl3):  = 144.9, 134.1, 117.6, 110.4, 86.7, 76.0,
70.4, 57.7, 36.8, 26.5, 22.3, 18.3.
To a stirred solution of 3015 (1.000 g, 6.016 mmol) in Et2O (100 mL) at
0 °C was added BuLi (3.4 mL, 1.8 M in hexane, 6.12 mmol) over 5 min
via syringe, giving a yellow suspension. After 1 h, TMSCl (1.0 mL, 860
mg, 7.9 mmol) was introduced via syringe over 5 min. The mixture
was stirred at 23 °C for 3 h, treated with sat. aq NaHCO3 (100 mL), and
the layers separated. The organic phase was dried (MgSO4), filtered,
and concentrated in vacuo to leave a yellow oil. Chromatography on
silica gel, eluting with Et2O/hexane (1:9), afforded 31 as a faint yellow
oil; yield: 849 mg (59%).
Anal. Calcd for C12H18O: C, 80.85; H, 10.18. Found: C, 80.69; H, 10.26.
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–R

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C.-A. Chang et al.
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Synthesis
9-(2-Propenyloxy)-1-nonen-7-yne (34)
35
The preceding general procedure was employed using NaH (324 mg,
13.5 mmol), 3-(2-propynyloxy)-1-propene (1.300 g, 13.52 mmol),
and 6-bromo-1-hexene (2.201 g, 13.50 mmol). The crude product
was chromatographed on silica gel, eluting with Et2O/pentane (3:50),
to afford 34 as a colorless oil; yield: 1.519 g (63%).
The preceding general synthetic procedure was employed using NaH
(216 mg, 9.00 mmol), 3-(2-propynyloxy)-1-propene (961 mg, 10.0
mmol), and 1-(2-bromoethyl)-2-methylidenecyclohexane (1.692 g,
8.330 mmol). The crude product was chromatographed on silica gel,
eluting with Et2O/hexane (1:50), to supply 35 as a colorless oil; yield:
952 mg (52%).
IR (film): 3080, 2980, 2940, 2860, 1645, 1445, 1355, 1135, 1085, 995,
915 cm–1
.
IR (film): 3080, 2930, 2850, 1640, 1445, 1350, 1135, 1080, 925, 890
cm–1
.
1H NMR (300 MHz, CDCl3):  = 5.89 (ddt, J = 17.2, 10.4, 5.8 Hz, 1 H),
5.78 (ddt, J = 17.0, 10.3, 6.6 Hz, 1 H), 5.28 (ddt, J = 17.2, 1.6, 1.6 Hz, 1
H), 5.18 (dtd, J = 10.4, 1.4, 1.2 Hz, 1 H), 4.98 (ddt, J = 17.2, 1.7, 1.6 Hz, 1
H), 4.92 (dtd, J = 10.2, 2.1, 1.2 Hz, 1 H), 4.11 (t, J = 2.1 Hz, 2 H), 4.03
(ddd, J = 5.7, 1.3, 1.3 Hz, 2 H), 2.21 (tt, J = 6.8, 2.1 Hz, 2 H), 2.05 (dt, J =
7.0, 7.0 Hz, 2 H), 1.50 (AA′BB′m, 4 H).
1H NMR (300 MHz, CDCl3):  = 5.89 (ddt, J = 17.2, 10.4, 5.8 Hz, 1 H),
5.28 (ddt, J = 17.3, 1.6, 1.6 Hz, 1 H), 5.18 (ddt, J = 10.3, 1.3, 1.2 Hz, 1 H),
4.65 (br s, 1 H), 4.55 (br s, 1 H), 4.12 (t, J = 2.1 Hz, 2 H), 4.03 (dt, J = 5.8,
1.3 Hz, 2 H), 2.19 (m, 4 H), 2.02 (m, 1 H), 1.84 (m, 1 H), 1.73 (m, 1 H),
1.62 (m, 1 H), 1.51 (m, 4 H), 1.26 (m, 1 H).
13C NMR (75 MHz, CDCl3):  = 138.5, 134.2, 117.6, 114.5, 86.8, 75.9,
13C NMR (75 MHz, CDCl3):  = 151.8, 134.2, 117.6, 106.1, 87.1, 75.8,
70.4, 57.7, 33.2, 28.02, 28.01, 18.6.
70.4, 57.8, 42.1, 34.4, 33.4, 31.0, 28.7, 24.0, 16.8.
Anal. Calcd for C12H18O: C, 80.85; H, 10.18. Found: C, 80.84; H, 10.04.
Methylidene-2-[5-(2-propenyloxy)-3-pentynyl]cyclohexane (35)
2-(2-Methylidenecyclohexyl)ethyl Methanesulfonate
To a stirred solution of 2-(2-methylidenecyclohexyl)ethanol44 (2.137
g, 15.24 mmol) and MsCl (1.3 mL, 1.9 g, 17 mmol) in CH2Cl2 (50 mL) at
0 °C was added Et3N (2.2 mL, 1.6 g, 16 mmol) dropwise via syringe
over 2 min, causing the formation of a colorless precipitate. The mix-
ture was stirred for 12 h at r.t., diluted with hexane (80 mL) and H2O
(40 mL), and the separated aqueous phase extracted with hexane (30
mL). The combined organic layers were washed with H2O (50 mL),
dried (MgSO4), filtered, and concentrated in vacuo to yield 2-(2-me-
thylidenecyclohexyl)ethyl methanesulfonate44 as a colorless oil, to be
applied directly to the next reaction; yield: 3.192 g (96%).
Anal. Calcd for C15H22O: C, 82.52; H, 10.16. Found: C, 82.43; H, 10.10.
Attempted CpCo-Mediated Cycloisomerization of 18
Reactions were performed with 1–2 mmol of 18 or, on a smaller scale,
in NMR tubes with thoroughly degassed reagents and solvents. Their
progression was followed by GC, MS, TLC, and 1H/13C NMR spectrosco-
py, until all of 18 had disappeared or conversion stopped. When a
workup was executed, the reaction mixture was filtered through a
short column of neutral alumina, eluting with pentane/Et2O (95:5).
In a typical experiment, 18 (115 mg, 0.60 mmol) and CpCo(CO)2 (25
L, 33.8 mg, 0.19 mmol) in decalin (1:1 mixture of cis- and trans-iso-
mers; 10 mL) was heated to reflux for 4 h. The deep red solution slow-
ly turned brown with concurrent formation of a fine black precipi-
tate. After workup, the product oil (90 mg, 78% mass recovery)
showed a 1H NMR spectrum (CDCl3) in which the terminal alkene sig-
nal at  = 5.78 had disappeared and absorptions at  = 5.3 (m), 2.1 (m),
1.6 (m), 1.3 (m), and 0.9 (m) in the ratio of 1:2:1:2:1 were evident.
IR (film): 2920, 2850, 1640, 1445, 1355, 1170, 970, 955, 890, 835, 820,
790 cm–1
.
IR (film): 2950, 1450, 1380, 1330, 960 cm–1
.
1H NMR (300 MHz, CDCl3):  = 4.70 (br s, 1 H), 4.57 (br s, 1 H), 4.22 (m,
2 H), 2.94 (s, 3 H), 2.20 (m, 2 H), 2.05 (m, 2 H), 1.77–1.42 (m, 6 H), 1.31
(m, 1 H).
MS (EI, 70 eV): m/z (%) = 190 ([M+], 1), 175 (13), 161 (50), 147 (50),
133 (44), 122 (65), 107 (71), 93 (83), 79 (84), 67 (83), 55 (83), 41
(100).
1-(2-Bromoethyl)-2-methylidenecyclohexane
In another experiment, 18 (255 mg, 1.34 mmol) and CpCo(CO)2 (50
L, 67.6 mg, 0.38 mmol) in boiling m-xylene (10 mL) was irradiated
with a projector lamp for 2 h, the light turned off, and reflux contin-
ued for another 4 h. Chromatography on alumina, eluting with
Et2O/pentane (1:1), separated first an oil (159 mg, 62% mass recovery)
of similar composition to that above (1H NMR), followed by a purple
fraction of biscarbyne complex {[CpCo]3[3-trans-CH=CH(CH2)3CH3]2}
(14 mg, 20%).
1H NMR (90 MHz, CDCl3):  = 8.84 (dt, J = 15, 1.5 Hz, 2 H), 6.70 (dt, J =
15, 7.2 Hz, 2 H), 4.30 (s, 15 H), 2.37 (m, 4 H), 1.60 (m, 8 H), 1.05 (t, J =
8 Hz, 6 H).
To a stirred solution of 2-(2-methylidenecyclohexyl)ethyl methane-
sulfonate (3.187 g, 14.60 mmol) in acetone (50 mL) at r.t. was added
anhyd LiBr (2.606 g, 30.01 mmol) in one portion. After 24 h, the sol-
vent was removed in vacuo at 0 °C, pentane (60 mL) and H2O (30 mL)
were added to the residue, and the separated aqueous layer extracted
with pentane (20 mL). The combined organic phases were washed
with H2O, dried (MgSO4), filtered, and concentrated in vacuo at 0 °C.
Chromatography on silica gel, eluting with pentane, gave 1-(2-bro-
moethyl)-2-methylidenecyclohexane44 as a colorless oil; yield: 2.609
g (88%).
IR (film): 3170, 2930, 2860, 1645, 1445, 1260, 1240, 1210, 895 cm–1
.
MS (EI, 70 eV): m/z (%) = 686 ([M+], 11), 578 (12), 562 (43), 438 (1),
314 (2), 213 (13), 199 (37), 189 (76), 97 (40), 71 (51), 69 (61), 57
(100).
1H NMR (300 MHz, CDCl3):  = 4.68 (br s, 1 H), 4.58 (br s, 1 H), 3.40 (m,
2 H), 2.28 (m, 1 H), 2.16 (m, 2 H), 2.01 (m, 1 H), 1.79 (m, 2 H), 1.53 (m,
4 H), 1.28 (m, 1 H).
13C NMR (75 MHz, CDCl3):  = 150.9, 106.6, 41.5, 35.1, 34.2, 33.3, 32.3,
Allylic Ether Cyclizations with CpCo(CO)2; General Procedure
28.5, 23.9.
A solution of CpCo(CO)2 (0.2 or 1 equiv) and the enynene in anhyd,
degassed, alkene-free PhMe (5–10 mL) was introduced via syringe
pump over several h to boiling, stirred, anhyd, degassed, alkene-free
PhMe (25–35 mL), contained in a 100 mL round-bottomed flask that
had been pretreated with hexamethyldisilazane. The vessel was irra-
diated with a filtered (Corning GS0-52-1, 340 nm cutoff) slide projec-
Anal. Calcd for C9H15Br: C, 53.22; H, 7.44. Found: C, 53.44; H, 7.49.
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–R

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C.-A. Chang et al.
Paper
Synthesis
tor lamp (Sylvania ELH 120 V, 300 W) controlled by a voltage regulator
set at 50 V during the entire addition to ensure continuous decarbon-
ylation of CpCo(CO)2. Boiling was sustained for several hours, until all
of the starting material had disappeared, the mixture cooled to r.t.,
and the volatiles were removed by vacuum transfer. The orange-
brown residue was chromatographed on silica gel, eluting with
Et2O/hexane.
2-(4-Bromophenyl)-2-oxoethyl trans-4-Methyl-3-oxacyclopen-
tanecarboxylate (38)
A solution of 37 (250 mg, 1.92 mmol) in H2O (3 mL) stirred at r.t. was
treated with a few crystals of phenolphthalein and a sufficient num-
ber of drops of aq 3 N NaOH to turn the solution pink. Enough HCl
(0.3 N) was then added to discharge the pink color, followed by 2-bro-
mo-1-(4-bromophenyl)-1-ethanone (500 mg, 1.80 mmol) in EtOH
(17 mL). A precipitate formed, which dissolved on heating to reflux
for 2 h. The EtOH was removed in vacuo, the residue covered with H2O
(20 mL), and the mixture extracted with CH2Cl2 (2 × 30 mL). The com-
bined organic layers were dried (MgSO4), filtered, and concentrated in
vacuo to give a yellow oil. Crystallization from hexane provided 38 as
a colorless solid; yield: 300 mg (51%); mp 74–75 °C.
Allylic Ether Cyclizations with CpCo(CH2=CH2)2; General Procedure
To CpCo(CH2=CH2)2 (100 mg, 0.56 mmol) in PhMe (2 mL) at 0 °C was
added the enynene (1 equiv) dropwise by syringe over a few min and
the mixture allowed to stir at r.t. for several h. The color changed from
deep-brown to dark red. To complete conversion, the mixture was
heated 50 °C for several min. The solvent was removed in vacuo and
the residue purified by chromatography on basic Al2O3, eluting with
Et2O/hexane. The so-obtained dark red or dark orange neat oils were
stable to air for several h, but decomposed relatively rapidly in solu-
tion.
IR (KBr): 2930, 2880, 1735, 1705, 1590, 1425, 1385, 1190, 1080, 985,
930, 830, 815 cm–1
.
1H NMR (250 MHz, CDCl3):  = 7.74 (d, J = 8.6 Hz, 2 H), 7.61 (d, J = 8.6
Hz, 2 H), 5.30 (ABq, 2 H), 4.06 (m, 3 H), 3.38 (dd, J = 8.1, 7.6 Hz, 1 H),
2.82 (ddd, J = 7.4, 7.4, 7.4 Hz, 1 H), 2.68 (dddq, J = 7.0, 7.0, 6.9, 6.9 Hz, 1
H), 1.18 (d, J = 6.7 Hz, 3 H).
13C NMR (75 MHz, CDCl3):  = 190.9, 172.9, 132.7, 132.2, 129.2, 129.1,
75.2, 70.3, 65.9, 51.5, 38.8, 17.2.
MS (EI, 70 eV): m/z (%) = 328 ([M+], 0.1), 326 ([M+], 0.1), 200 (60), 198
(61), 185 (83), 183 (84), 157 (41), 155 (43), 129 (70), 113 (56), 84 (40),
83 (75), 76 (47), 75 (35), 69 (49), 57 (70), 55 (100).
trans-3-Methyl-4-(4-methyloxacyclopent-3-yl)furan (36)
CpCo(CO)2 (510 L, 689 mg, 3.82 mmol) and 19 (3.600 g, 21.66 mmol)
were subjected to the general cyclization conditions over 12 h to re-
sult in 36 as a colorless oil; yield: 2.524 g (70%).
IR (film): 2960, 2930, 2870, 1465, 1390, 1365, 1150, 1055, 870, 790
cm–1
.
Anal. Calcd for C14H15BrO4: C, 51.40; H, 4.62. Found: C, 51.33; H, 4.60.
1H NMR (250 MHz, CDCl3):  = 7.18 (s, 1 H), 7.14 (s, 1 H), 4.14 (dd, J =
8.0, 7.7 Hz, 1 H), 4.08 (dd, J = 7.9, 7.5 Hz, 1 H), 3.60 (dd, J = 8.4, 8.4 Hz,
1 H), 3.43 (dd, J = 8.2, 8.2 Hz, 1 H), 2.72 (ddd, J = 8.3, 8.3, 8.3 Hz, 1 H),
2.28 (m, 1 H), 1.96 (s, 3 H), 1.05 (d, J = 6.6 Hz, 3 H).
13C NMR (75 MHz, CDCl3):  = 140.0, 138.6, 124.7, 119.8, 75.1, 73.7,
43.0, 40.3, 16.0, 8.48.
1,4-Bis(2-deuterio-2-propenyloxy)-2-butyne (19-d2)
To a slurry of NaH (744 mg, 31.00 mmol) in DMSO (25 mL) at r.t. was
added 2-butyne-1,4-diol (1.310 g, 15.22 mmol) in DMSO (10 mL) over
15 min via syringe. The brown mixture was stirred until H2 evolution
had ceased (3 h) and then 3-chloro-1-propene-2-d29 (2.360 g, 30.44
mmol) in DMSO (5 mL) introduced via syringe, while keeping the
temperature below 30 °C. After stirring for 18 h, the mixture was
treated with sat. aq NaHCO3 (60 mL) and hexane (75 mL). The layers
were separated and the aqueous phase extracted with hexane (2 × 25
mL). The combined organic layers were washed with brine (50 mL),
dried (Na2SO4), filtered, and concentrated in vacuo to furnish a yellow
oil. Kugelrohr distillation provided 19-d2 as a colorless oil; yield: 961
mg (38%); bp 107–110 °C/12 Torr (Lit. 1912 bp 104–106/10 Torr).
Anal. Calcd for C10H14O2: C, 72.26; H, 8.49. Found: C, 71.93; H, 8.55.
trans-4-Methyl-3-oxacyclopentanecarboxylic Acid (37)
Through a solution of 36 (400 mg, 2.41 mmol) in CH2Cl2/MeOH (1:3,
35 mL) was passed ozone at –78 °C until a green color persisted. The
mixture was purged with N2 and treated with aq H2O2 (8 mL, 30% by
wt) and aq 3 N NaOH (4 mL). After stirring at 0 °C for 1.5 h, the vola-
tiles were removed in vacuo, and the residue was extracted with Et2O
(30 mL). The pH of the aqueous layer was adjusted to 2 with aq HCl
and the solution saturated with NaCl, followed by extraction with
Et2O (3 × 20 mL). The combined organic phases were dried (MgSO4),
filtered, concentrated in vacuo, and the resulting pink oil subjected to
Kugelrohr distillation to afford 37 as a colorless oil; yield: 201 mg
(64%); bp 125–131 °C/13 Torr.
1H NMR (250 MHz, CDCl3):  = 5.87 (m, 0.06 H), 5.28 (narrow m, 2 H),
5.18 (narrow m, 2 H), 4.17 (s, 4 H), 4.03 (br s, 4 H).
trans-3-Methyl-4-(4-deuterio-4-deuteriomethyloxacyclopent-3-
yl)furan (36-d2)
The deuterated enynene 19-d2 (168 mg, 1.00 mmol) was subjected to
the general enynene cyclization procedure in the presence of
CpCo(CO)2 (42 L, 57 mg, 0.32 mmol) over 6 h. The orange-brown res-
idue was chromatographed on silica gel, eluting with Et2O/hexane
(1:9), to give 36-d2 as a colorless oil; yield: 125 mg (74%).
IR (film): 3300–2800 (br), 2970, 2870, 1720, 1460, 1415, 1380, 1180,
1055, 915 cm–1
.
1H NMR (300 MHz, CDCl3):  = 9.10 (br s, 1 H), 4.05 (m, 3 H), 3.36 (dd,
J = 7.9, 7.9 Hz, 1 H), 2.67 (ddd, J = 7.3, 7.3, 7.3 Hz, 1 H), 2.57 (dddq, J =
7.0, 7.0, 6.9, 6.9 Hz, 1 H), 1.13 (d, J = 6.8 Hz, 3 H).
IR (film): 2930, 2860, 2180, 1675, 1440, 1280, 1140, 1050, 920, 785
cm–1
.
13C NMR (75 MHz, CDCl3):  = 179.2, 75.2, 70.1, 51.5, 38.5, 17.1.
1H NMR (250 MHz, CDCl3):  = 7.18 (s, 1 H), 7.14 (s, 1 H), 4.14 (dd, J =
8.0, 7.7 Hz, 1 H), 4.08 (d, J = 7.9 Hz, 1 H), 3.60 (dd, J = 8.4, 8.4 Hz, 1 H),
3.43 (d, J = 8.2 Hz, 1 H), 2.72 (dd, J = 8.3, 8.3 Hz, 1 H), 2.28 (m, 0.07 H),
1.96 (s, 3 H), 1.05 (br s, 2.06 H).
MS (EI, 70 eV): m/z (%) = 130 ([M+], 2), 112 (5), 100 (29), 88 (27), 85
(36), 82 (28), 73 (100).
HRMS (EI, 70 eV): m/z [M+] calcd for C6H10O3: 130.0630; found:
130.0625.
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–R

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C.-A. Chang et al.
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Synthesis
Diene Complex 39
Anal. Calcd for C33H49CoO4: C, 69.70; H, 8.68. Found: C, 69.32; H, 8.63.
CpCo(CH2=CH2)2 (100 mg, 0.56 mmol) and enynene 19 (93 mg, 0.56
mmol) were transformed according to the general cyclization proto-
col and subjected to chromatography on alumina, eluting with hex-
ane/Et2O (10:1), to sequester 39 as a dark red oil; yield: 114 mg (70%).
4-Methyl-3-(4,4-dimethyloxacyclopent-3-yl)furan (43)
Enynene 22 (2.381 g, 13.21 mmol) and CpCo(CO)2 (381 L, 514 mg,
2.86 mmol) were subjected to the general cyclization protocol over 10
h. Chromatography on silica gel, eluting with Et2O/hexane (1:4), pre-
sented 43 as a colorless oil; yield: 1.856 g (78%).
IR (film): 2970, 2930, 2850, 1675, 1473, 1459, 1377, 1342, 1265,
1113, 1080, 1063, 1042, 1027, 943, 910, 741 cm–1
.
1H NMR (300 MHz, PhMe-d8):  = 4.59 (br s, 2 H), 4.53 (d, J = 9 Hz, 1
H), 4.33 (s, 5 H), 4.32 (d, J = 9 Hz, 1 H), 3.64 (d, J = 9 Hz, 1 H), 3.40 (m, 3
H), 1.86 (d, J = 2 Hz, 1 H), 1.10 (d, J = 7 Hz, 3 H), 0.55 (m, 1 H), 0.28 (d,
J = 2 Hz, 1 H).
13C NMR (75 MHz, CDCl3, DEPT):  = 100.0 (Cquat), 95.8 (Cquat), 81.9
(CH), 74.9 (CH2), 73.9 (CH2), 73.7 (CH2), 73.4 (CH2), 59.8 (Cquat), 34.7
(CH), 23.2 (CH2), 21.0 (CH3).
IR (film): 2960, 2925, 2870, 1465, 1385, 1365, 1150, 1055, 920, 870,
790 cm–1
.
1H NMR (250 MHz, CDCl3):  = 7.17 (br s, 2 H), 4.18 (dd, J = 8.2, 8.0 Hz,
1 H), 3.82 (dd, J = 8.6, 8.5 Hz, 1 H), 3.63 (ABq, 2 H), 2.92 (dd, J = 8.3, 8.2
Hz, 1 H), 1.96 (s, 3 H), 1.09 (s, 3 H), 0.83 (s, 3 H).
13C NMR (75 MHz, CDCl3):  = 139.6, 139.4, 122.5, 120.3, 80.7, 73.1,
45.00, 41.9, 25.8, 21.6, 8.63.
MS (EI, 70 eV): m/z (%) = 290 ([M+], 16), 286 (2), 262 (8), 260 (8), 217
(7), 166 (7), 124 (100).
Anal. Calcd for C11H16O2: C, 73.30; H, 8.95. Found: C, 73.43; H, 9.02.
Diene Complex 44
Cyclohexadiene Complexes 40 and 41
CpCo(CH2=CH2)2 (100 mg, 0.56 mmol) and enynene 22 (101 mg, 0.56
mmol) were transformed according to the general cyclization routine
over 1 d and subjected to chromatography on alumina, eluting with
hexane/Et2O (1:1), to secure 44 as a dark red oil; yield: 111 mg (65%).
Enynene 20 (194 mg, 1.00 mmol) and CpCo(CO)2 (127 L, 171 mg,
0.95 mmol) were subjected to the general enynene cyclization condi-
tions over 6 h. Chromatography on silica gel, eluting with Et2O/hex-
ane (3:7), afforded first 40 as an air-sensitive orange syrup; yield: 70
mg (27%, based on 20).
1H NMR (250 MHz, CDCl3):  = 4.97 (br s, 3 H), 4.90 (br s, 3 H), 4.62 (s,
5 H), 4.54 (m, 1 H), 4.16 (m, 1 H), 3.96 (m, 12 H), 3.48 (ABm, 2 H), 1.89
(d, J = 15 Hz, 1 H), 1.74 (br s, 9 H), 1.21 (d, J = 15 Hz, 1 H), 0.79 (s, 3 H).
IR (film): 3100, 2970, 2930, 2840, 1670, 1470, 1415, 1390, 1370,
1360, 1340, 1265, 1110, 1080, 1060, 1020, 950, 920, 890, 810, 760,
710 cm–1
.
1H NMR (300 MHz, PhMe-d8):  = 4.63 (d, J = 8 Hz, 1 H), 4.61 (br s, 2
H), 4.37 (d, J = 8 Hz, 1 H), 4.35 (s, 5 H), 3.48 (ABq, 2 H), 3.45 (d, J = 8 Hz,
1 H), 3.21 (d, J = 8 Hz, 1 H), 1.78 (d, J = 4 Hz, 1 H), 1.22 (s, 3 H), 0.69 (d,
J = 4 Hz, 1 H), 0.24 (s, 3 H).
13C NMR (75 MHz, C6D6, DEPT):  = 100.3 (Cquat), 94.8 (Cquat), 83.7
(CH2), 82.2 (CH), 79.7 (CH2), 75.3 (CH2), 74.4 (CH2), 65.0 (Cquat), 41.2
(Cquat), 29.8 (CH3), 27.1 (CH3), 22.0 (CH2).
MS (FAB, 70 eV): m/z (%) = 512 ([M+], 83), 511 (100).
A second band contained 41, also as an air-sensitive orange syrup;
yield: 70 mg (27%, based on 20).
1H NMR (250 MHz, CDCl3):  = 4.96 (br s, 3 H), 4.87 (br s, 3 H), 4.63 (s,
5 H), 4.56 (m, 1 H), 4.30 (m, 1 H), 3.95 (m, 11 H), 3.47 (ABm, 2 H), 2.70
(d, J = 7.5 Hz, 1 H), 1.74 (br s, 9 H), 1.43 (s, 3 H), 1.03 (d, J = 15 Hz, 1 H),
0.06 (d, J = 15 Hz, 1 H).
MS (EI, 70 eV): m/z (%) = 304 ([M+], 39), 180 (36), 124 (100), 109 (89),
108 (78), 95 (56), 79 (56), 66 (55).
13C NMR (50 MHz, CDCl3):  = 142.6, 142.51, 142.47, 111.94, 111.89,
111.55, 90.7, 85.5, 81.0, 75.8, 75.7, 74.89, 74.85, 74.52, 74.08, 68.6,
67.8, 66.7, 66.0, 51.0, 32.4, 29.2, 19.5 (br, 3 C).
cis-3-(1-Methylethyl)-4-(4-methyltetrahydrofuran-3-yl)furan(45)
and trans-3-(1-Methylethyl)-4-(4-methyltetrahydrofuran-3-
yl)furan (46)
HRMS (FAB, 70 eV): m/z [M+] calcd for C29H41CoO4: 512.2337; found:
512.2341.
Enynene 23 (230 mg, 1.18 mmol) and CpCo(CO)2 (127 L, 172 mg,
0.95 mmol) were subjected to the general cyclization technique over
10 h. The orange-brown crude product was chromatographed, eluting
with Et2O/hexane (1:9), to give an inseparable mixture of 45 and 46
in the ratio 55:45; yield: 54 mg (23%).
Cyclohexadiene Complex 42
Enynene 21 (198 mg, 0.891 mmol) and CpCo(CO)2 (51 L, 69 mg, 0.38
mmol) were subjected to the general cyclization method over 6 h.
Chromatography on silica gel, eluting with Et2O/hexane (3:7), afford-
ed 42 as an orange syrup; yield: 100 mg (46%).
45
1H NMR (300 MHz, CDCl3):  = 7.16 (br s, 1 H), 7.13 (br s, 1 H), 4.07
(dd, J = 8.0, 7.4 Hz, 1 H), 4.05 (dd, J = 8.0, 7.4 Hz, 1 H), 3.78 (dd, J = 7.9,
7.7 Hz, 1 H), 3.50 (dd, J = 8.3, 5.6 Hz, 1 H), 3.26 (ddd, J = 7.1, 7.1, 7.1 Hz,
1 H), 2.67 (sept, J = 6.6 Hz, 1 H), 2.52 (dddq, J = 7.0, 7.0, 6.9, 5.7 Hz, 1
H), 1.21 (d, J = 6.9 Hz, 3 H), 1.17 (d, J = 7.4 Hz, 3 H), 0.74 (d, J = 6.9 Hz,
3 H).
1H NMR (300 MHz, CDCl3):  = 5.37 (tsept, J = 7.0, 1.4 Hz, 1 H), 5.32
(tsept, J = 7.0, 1.4 Hz, 2 H), 4.51 (s, 5 H), 4.48 (d, J = 11.0 Hz, 1 H), 4.45
(d, J = 11.3 Hz, 1 H), 4.24 (d, J = 11.0 Hz, 1 H), 4.17 (m, 1 H), 4.10 (d, J =
11.4 Hz, 1 H), 4.09 (d, J = 9.7 Hz, 1 H), 4.04 (m, 3 H), 3.88 (m, 3 H), 3.82
(d, J = 10.0 Hz, 1 H), 3.52 (dd, J = 7.1, 7.1 Hz, 1 H), 3.25 (d, J = 10.1 Hz 1
H), 2.68 (dd, J = 11.5, 7.1 Hz, 1 H), 2.24 (dd, J = 11.5, 7.1 Hz, 1 H), 1.73
(s, 3 H), 1.72 (s, 6 H), 1.67 (s, 3 H), 1.65 (s, 3 H), 1.64 (s, 3 H), 1.10 (s, 3
H), 0.57 (s, 3 H).
46
1H NMR (300 MHz, CDCl3):  = 7.20 (br s, 1 H), 7.14 (br s, 1 H), 4.18
(dd, J = 7.9, 7.8 Hz, 1 H), 4.10 (dd, J = 8.1, 7.7 Hz, 1 H), 3.56 (dd, J = 8.3,
8.3 Hz, 1 H), 3.44 (dd, J = 8.2, 8.2 Hz, 1 H), 2.77 (ddd, J = 8.3, 8.1, 8.1 Hz,
1 H), 2.69 (sept, J = 6.6 Hz, 1 H), 2.26 (dddq, J = 7.8, 7.4, 7.3, 7.3 Hz, 1
H), 1.19 (d, J = 7.0 Hz, 3 H), 1.17 (d, J = 7.4 Hz, 3 H), 1.07 (d, J = 7.1 Hz,
3 H).
13C NMR (75 MHz, CDCl3, DEPT):  = 136.2 (Cquat), 135.8 (Cquat), 135.6
(Cquat), 121.9 (CH), 121.8 (CH), 121.6 (CH), 90.1 (Cquat), 87.4 (Cquat), 81.0
(CH), 74.1 (CH2), 72.1 (CH2), 70.2 (CH2), 67.3 (CH2), 67.2 (CH2), 67.1
(CH2), 66.6 (CH2), 66.5 (Cquat), 66.1 (CH2), 65.4 (Cquat), 61.1 (CH), 31.6
(CH3), 28.8 (Cquat), 27.2 (CH3), 25.76 (2 CH3), 25.74 (CH3), 18.09 (CH3),
18.07 (2 CH3).
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–R

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C.-A. Chang et al.
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Synthesis
Diene Complexes 47 and 48
MS (EI, 70 eV): m/z (%) = 302 ([M+], 92), 300 (39), 243 (30), 230 (53),
124 (100), 73 (88), 59 (64).
CpCo(CH2=CH2)2 (100 mg, 0.56 mmol) and enynene 32 (92 mg, 0.56
mmol) were transformed according to the general cyclization scheme
over 1 d and subjected to chromatography on alumina, eluting with
hexane/Et2O (1:1), to yield an inseparable mixture of 47 and 48 in a
2:1 ratio as a dark red oil; yield: 145 mg (86%).
51
Yield: 268 mg (27%).
1H NMR (300 MHz, C6D6):  = 4.50 (s, 5 H), 4.48 (d, J = 9.7 Hz, 1 H),
4.42 (dd, J = 7.7, 7.5 Hz, 1 H), 3.61 (ABq, 2 H), 2.50 (m, 1 H), 2.08–1.51
(m, 8 H), 1.76 (br s, 1 H), 0.42 (d, J= 6.9 Hz, 3 H), 0.11 (br s, 1 H).
IR (film): 2970, 2930, 2860, 1740, 1470, 1270, 1110, 1090, 1080,
1020, 920, 810, 750 cm–1
.
1H NMR (300 MHz, PhMe-d8; tentative assignments):  (47) = 4.65 (m,
2 H), 4.36 (s, 5 H), 3.65 (ABq, 2 H), 2.4–1.2 (m, 6 H), 1.92 (br s, 1 H),
1.18 (d, J = 7 Hz, 3 H), 0.65 (m, 1 H), 0.47 (br s, 1 H);  (48) = 4.43 (m, 2
H), 4.41 (s, 5 H), 3.48 (m, 2 H), 2.4–1.2 (m, 6 H), 1.78 (br s, 1 H), 1.10
(d, J = 7 Hz, 3 H), 0.92 (m, 1 H), 0.36 (br s, 1 H).
13C NMR (75 MHz, C6D6, DEPT):  = 103.6 (Cquat), 99.3 (Cquat), 99.1
(Cquat), 97.6 (Cquat), 82.1 (CH), 81.3 (CH), 75.6 (CH2), 73.9 (CH2, 2 C),
73.7 (CH2), 60.5 (br, Cquat, 2 C), 35.5 (CH2), 34.8 (CH2), 34.2 (CH), 32.8
(CH2), 31.7 (CH), 26.7 (br, CH2, 2 C), 23.9 (CH2), 23.5 (CH2), 23.3 (CH3),
21.9 (CH2), 21.0 (CH3).
13C NMR (75 MHz, C6D6, DEPT):  = 95.9 (Cquat), 89.1 (Cquat), 82.1 (CH),
77.7 (CH2), 77.1 (CH2), 64.2 (Cquat), 40.5 (CH), 32.6 (CH2), 31.4 (CH2),
29.7 (CH2), 24.2 (CH2), 23.5 (CH2), 22.0 (CH3).
MS (EI, 70 eV): m/z (%) = 302 ([M+], 73), 300 (63), 243 (30), 230 (37),
124 (100), 59 (82).
(E)-3-Methyl-4-(2-methylenecyclohexylidene)oxacyclopentane
(52)
Note: Because of the air-sensitivity of 52, all operations were carried
out under argon in degassed solvents. To a mixture of 50 and 51
(1.7:1, 516 mg, 1.71 mmol) in DME (15 mL) at r.t. was added Cu-
Cl2·2H2O (1.023 g, 6.00 mmol) in one portion. The resulting green
solution was stirred for 15 min, followed by the addition of hexane
(30 mL) and H2O (100 mL). The mixture was shaken in a separatory
funnel, the sequestered organic layer washed with H2O (5O mL), dried
(MgSO4), filtered, concentrated in vacuo, and chromatographed on
silica gel, eluting with Et2O/hexane (1:9), to afford 52 as an air-sensi-
tive colorless oil; yield: 161 mg (53%).
MS (EI, 70 eV): m/z (%) = 288 ([M+], 74), 271 (33), 269 (30), 203 (100),
124 (65), 91 (57), 79 (43), 59 (50).
Anal. Calcd for C16H21CoO: C, 66.66; H, 7.34. Found: C, 66.75; H, 7.68.
3-(2,2-Dimethylcyclopentyl)-4-methylfuran (49)
Enynene 33 (250 mg, 1.40 mmol) and CpCo(CO)2 (76 L, 103 mg, 0.57
mmol) were subjected to the general cyclization protocol over 6 h.
Chromatography on silica gel, eluting with hexane, produced 49 as a
colorless oil; yield: 153 mg (59%).
IR (film): 3075, 2930, 2850, 1633, 1444, 1370, 1098, 1085, 1077,
1043, 972, 925, 895, 822, 700 cm–1
.
IR (film): 2955, 2925, 2870, 1465, 1380, 1365, 1155, 1055, 850, 785
1H NMR (250 MHz, CDCl3):  = 4.82 (br s, 1 H), 4.78 (br s, 1 H), 4.39 (d,
J = 13.0 Hz, 1 H), 4.24 (d, J = 13.0 Hz, 1 H), 3.83 (dd, J = 8.3, 5.9 Hz, 1 H),
3.56 (dd, J = 8.3, 2.9 Hz, 1 H), 3.03 (m, 1 H), 2.26 (m, 1 H), 2.03 (m, 3
H), 1.68 (m, 2 H), 1.52 (m, 2 H), 1.05 (d, J = 6.9 Hz, 3 H).
13C NMR (75 MHz, CDCl3, DEPT):  = 149.2 (Cquat), 136.2 (Cquat), 131.3
(Cquat), 109.0 (CH2), 76.0 (CH2), 69.6 (CH2), 37.4 (CH2), 36.1 (CH), 33.3
(CH2), 27.9 (CH2), 26.9 (CH2), 18.7 (CH3).
cm–1
.
1H NMR (250 MHz, CDCl3):  = 7.13 (s, 2 H), 2.52 (dd, J = 10.4, 7.8 Hz, 1
H), 2.00 (m, 1 H), 1.94 (s, 3 H), 1.70 (m, 3 H), 1.56 (m, 2 H), 0.97 (s, 3
H), 0.72 (s, 3 H).
13C NMR (75 MHz, CDCl3, DEPT):  = 139.7 (CH), 138.9 (CH), 125.9
(Cquat), 120.6 (Cquat), 45.2 (CH), 41.8 (CH2), 41.3 (Cquat), 31.8 (CH2), 28.6
(CH3), 23.0 (CH3), 21.3 (CH2), 8.85 (CH3).
Anal. Calcd for C12H18O2: C, 80.85; H, 10.18. Found: C, 80.85; H, 10.16.
MS (EI, 70 eV): m/z (%) = 178 ([M+], 91), 163 (26), 135 (34), 122 (24),
109 (33), 108 (29), 96 (100), 71 (35).
HRMS (EI, 70 eV): m/z [M+] calcd for C12H18O: 178.1358; found:
178.1358.
3-Methyl-4-[(1R*,3aS*,7aS*)-7a-methyloctahydro-1-indenyl]fu-
ran and (53) 3-Methyl-4-[(1S*,3aS*,7aS*)-7a-methyloctahydro-1-
indenyl]furan (54)
Anal. Calcd for C12H18O: C, 80.85; H, 10.18. Found: C, 80.96; H, 10.09.
Enynene 35 (380 mg, 1.74 mmol) and CpCo(CO)2 (178 L, 240 mg,
1.34 mmol) were subjected to the general cyclization conditions over
5 h. Chromatography on silica gel, eluting with hexane, afforded an
inseparable (except by GC) mixture of 53 and 54 as a colorless oil, in
the ratio 4:1, as determined by capillary GC and 1H NMR spectrosco-
py; yield: 221 mg (58%).
Diene Complexes 50 and 51
Enynene 34 (600 mg, 3.37 mmol) and CpCo(CO)2 (431 L, 582 mg,
3.23 mmol) were subjected to the general cyclization routine over 8.5
h. Chromatography on silica gel, eluting with Et2O/hexane (1:20),
gave first 51, followed by 50 as orange oils.
IR (film): 2950, 2930, 2870, 1462, 1445, 1372, 1153, 1055, 855, 783
cm–1
.
50
Yield: 446 mg (46%).
53
1H NMR (300 MHz, C6D6):  = 4.38 (s, 5 H), 3.81 (s, 2 H), 3.58 (appar-
ent d, J = 3.3 Hz, 2 H), 2.38 (m, 4 H), 1.85 (m, 2 H), 1.83 (d, J = 1.9 Hz, 1
H), 1.70 (m, 1 H), 1.49 (m, 1 H), 1.17 (d, J = 7.0 Hz, 3 H), 0.81 (qd, J =
6.9, 3.4 Hz, 1 H), 0.45 (br s, 1 H).
1H NMR (300 MHz, C6D6; assigned from the mixture of 53 and 54):  =
7.14 (d, J = 1.5 Hz, 1 H), 7.08 (m, 1 H), 2.51 (dd, J = 10.6, 8.9 Hz, 1 H),
1.94 (m, 1 H), 1.84 (d, J = 1.0 Hz, 3 H), 1.72–1.00 (m, 12 H), 0.91 (s, 3
H).
13C NMR (75 MHz, C6D6, DEPT):  = 97.3 (Cquat), 91.0 (Cquat), 81.8 (CH),
73.3 (CH2), 71.9 (CH2), 61.9 (Cquat), 34.9 (CH), 32.8 (CH2), 31.0 (CH2),
28.4 (CH2), 24.4 (CH2), 23.6 (CH2), 20.0 (CH3).
13C NMR (75 MHz, CDCl3, DEPT; assigned from the mixture of 53 and
54):  = 139.86 (CH), 138.79 (CH), 124.63 (Cquat), 120.66 (Cquat), 47.5
(CH), 45.5 (CH), 42.3 (Cquat), 29.4 (CH2), 28.05 (CH2), 25.1 (CH2), 24.8
(CH2), 23.4 (CH3), 21.8 (CH2), 20.7 (CH2), 8.84 (CH3).
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–R

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C.-A. Chang et al.
Paper
Synthesis
GCMS: m/z (%) = 218 ([M+], 18), 203 (5), 122 (14), 109 (31), 108 (100),
96 (38), 95 (11), 79 (16), 77 (10), 41 (14).
syringe over 30 sec. After 2 h, TMSCl (444 L, 380 mg, 3.50 mmol) was
introduced rapidly via syringe and the mixture allowed to warm to r.t.
Treatment with aq 1 N HCl (15 mL) was followed by vigorous stirring
of the resulting biphasic mixture for 4.5 h. The layers were separated,
and the aqueous phase was extracted with Et2O (3 × 20 mL). The com-
bined organic portions were dried (MgSO4), filtered, and concentrated
in vacuo to afford a pink oil. This material was chromatographed on
silica gel, eluting with Et2O/hexane (1:9), to give a 4:1 mixture of 57
and 58 as a pink oil; yield: 62 mg (42%).
54
1H NMR (300 MHz, C6D6; assigned from the mixture of 53 and 54):  =
7.11 (d, J = 1.4 Hz, 1 H), 7.06 (m, 1 H), 2.93 (dd, J = 8.8, 8.6 Hz, 1 H),
2.11 (m, 1 H), 1.83 (d, J = 2.0 Hz, 3 H), 1.72–1.00 (m, 12 H), 0.75 (s, 3
H).
13C NMR (75 MHz, CDCl3, DEPT; assigned from the mixture of 53 and
54):  = 139.94 (CH), 138.75 (CH), 124.76 (Cquat), 120.78 (Cquat), 45.2
(CH), 43.6 (Cquat), 39.2 (CH), 34.3 (CH2), 29.9 (CH2), 28.9 (CH2), 28.09
(CH2), 24.3 (CH2), 24.0 (CH3), 22.4 (CH2), 8.88 (CH3).
IR (film): 2960, 2930, 2860, 1705, 1470, 1450, 1355, 1210, 1165 cm–1
.
57
1H NMR (300 MHz, CDCl3/TMS; assigned from the mixture of 57 and
58):  = 2.69 (dd, J = 9.1, 9.0 Hz, 1 H), 2.13 (s, 3 H), 2.09 (m, 1 H), 1.73–
0.88 (m, 13 H), 1.25 (s, 3 H) (Lit.37  = 1.27).
GCMS: m/z (%) = 218 ([M+], 16), 122 (12), 108 (100), 96 (28), 79 (16),
77 (10), 41 (15).
Anal. Calcd for C15H22O: C, 82.52; H, 10.16. Found: C, 82.27; H, 10.13.
58
(1R*,3aS*,7aS*)-7a-Methyloctahydroindene-1-carboxylic Acid (55)
and (1S*,3aS*,7aS*)-7a-Methyloctahydroindene-1-carboxylic Acid
(56)
1H NMR (300 MHz, CDCl3/TMS; assigned from the mixture of 57 and
58):  = 2.98 (dd, J = 9.0, 7.2 Hz, 1 H), 2.12 (s, 3 H), 2.09 (m, 1 H), 1.73–
0.88 (m, 13 H), 0.87 (s, 3 H) (Lit.37  = 0.88).
Ozone was passed through a mixture of 53 and 54 (4:1, 320 mg, 1.47
mmol) in CH2Cl2 (15 mL) at –78 °C until a green color persisted. Excess
ozone was purged with O2, the solution warmed to r.t., and the sol-
vent removed in vacuo to give a yellow oil. The residue was stirred
with added H5IO6 (1.071 g, 4.698 mmol), acetone (3 mL), and aq H2SO4
(6 M, 2 mL) for 6 h, the solution partitioned between H2O (50 mL) and
Et2O (20 mL) with shaking, and the separated aqueous phase washed
with Et2O (3 × 15 mL). The combined organic layers were extracted
with sat. aq NaHCO3 (2 × 25 mL) and the resulting basic solution acid-
ified to pH 2 with aq 6 N HCl. This mixture was washed with Et2O (4 ×
10 mL), and the combined Et2O solutions were dried (MgSO4), filtered,
and concentrated in vacuo to afford a 4:1 mixture of 55 and 56 as a
waxy pink solid, used as such in their conversion into 57 and 58;
yield: 203 mg (76%).
Funding Information
This work was funded by the NIH (GM 22479) and NSF (CHE
0907800)
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e
a
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2
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7
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Acknowledgment
S.G. thanks the Alexander von Humboldt Foundation for a Feodor Ly-
nen Research Fellowship. We are indebted to Professor Roland Boese,
Universität Duisburg-Essen, for the X-ray structural determination of
38, and Dr. Jordi Benet-Buchholz, Institute of Chemical Research of
Catalonia (ICIQ) Tarragona, for updating the associated cif file.
IR (KBr): 3000 (br), 2973, 2930, 2860, 1705, 1465, 1455, 1420, 1380,
1290, 1255, 1235, 1123, 1083, 1047, 890, 875 cm–1
.
Supporting Information
55
1H NMR (300 MHz, CDCl3; assigned from the mixture of 55 and 56): 
= 2.52 (dd, J = 9.0, 8.8 Hz, 1 H), 2.09 (m, 1 H), 1.97–1.08 (m, 13 H), 1.19
(s, 3 H).
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1690727.
S
u
p
p
orti
n
gInformati
o
n
S
u
p
p
orti
n
gInformati
o
n
13C NMR (75 MHz, CDCl3, DEPT; assigned from the mixture of 55 and
56):  = 180.63 (Cquat), 56.4 (CH), 45.9 (Cquat), 43.7 (CH), 27.81 (CH2),
25.7 (CH2), 24.04 (CH2), 23.59 (CH3), 23.55 (CH2), 21.77 (CH2), 20.10
(CH2).
References
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1-[(1R*,3aS*,7aS*)-7a-Methyloctahydroinden-1-yl]-1-ethanone
(57) and 1-[(1S*,3aS*,7aS*)-7a-Methyloctahydroinden-1-yl]-1-eth-
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© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–R