Classical versus nonstatistical behavior in the C2-C 6/ene cyclization of enyne-allenes: Intramolecular kinetic isotope effects and radical clock reactions

Article abstract of DOI:10.1055/s-0029-1218799

The effects of aryl groups on the mechanism of the C²-C ⁶/ene cyclization of enyne-allenes were studied by means of radical clock openings and intramolecular kinetic isotope effects. Upon attachment of a single aryl group at either the alkyne or the allene terminus, the thermal reaction proceeds by a stepwise mechanism that shows significant nonstatistical dynamic effects. Despite this, we were able to intercept the intermediate diradical intramolecularly by using the ultrafast diphenylcyclopropyl radical clock reaction. When aryl groups were present at both the alkyne and allene termini, the intramolecular kinetic isotope effects were consistent with a classical stepwise mechanism. The present study thus demonstrates the shift in reaction mechanism from a nonstatistical stepwise mechanism to a classical stepwise behavior, depending on the substituents. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0029-1218799

PAPER
2213
Classical Versus Nonstatistical Behavior in the C2–C6/Ene Cyclization of
Enyne–Allenes: Intramolecular Kinetic Isotope Effects and Radical Clock
Reactions
2
6
C
–C /Ene
Cycliz
h
ation of Eny
a
ne–Allene
s
ndrasekhar Vavilala,a,† Jan W. Bats,b Michael Schmittel*a
a
FB 8 (Chemie-Biologie), Universität Siegen, Adolf-Reichwein-Str., 57068 Siegen, Germany
Institut für Organische Chemie und Chemische Biologie, Johann Wolfgang Goethe-Universität, Max-von-Laue-Str. 7,
60438 Frankfurt am Main, Germany
b
Fax +49(271)7403270; E-mail: schmittel@chemie.uni-siegen.de
Received 15 April 2010
Dedicated to Professor Rolf Huisgen on the occasion of his 90th birthday
The thermal C2–C6 cyclization of enyne–allenes,4 a regio-
variant of the well-known Myers–Saito cyclization,5 has
been extensively studied both mechanistically6 and theo-
retically,7 because of its importance in the synthesis of
Abstract: The effects of aryl groups on the mechanism of the C2–
C6/ene cyclization of enyne–allenes were studied by means of radi-
cal clock openings and intramolecular kinetic isotope effects. Upon
attachment of a single aryl group at either the alkyne or the allene
terminus, the thermal reaction proceeds by a stepwise mechanism complex carbocycles8 and in DNA cleavage.9 On the basis
that shows significant nonstatistical dynamic effects. Despite this,
of the trapping of an intermediate with cyclohexa-1,4-di-
ene,6e the observation of DNA double-strand cleavage,9
we were able to intercept the intermediate diradical intramolecular-
ly by using the ultrafast diphenylcyclopropyl radical clock reaction.
and computational studies,6e we proposed a diradical
When aryl groups were present at both the alkyne and allene termi-
mechanism for the C2–C6 cyclization similar to that of the
ni, the intramolecular kinetic isotope effects were consistent with a
Myers-Saito cyclization. In one variant of the thermal C2–
classical stepwise mechanism. The present study thus demonstrates
C6 cyclization of enyne–allenes, a formal ene reaction was
the shift in reaction mechanism from a nonstatistical stepwise
mechanism to a classical stepwise behavior, depending on the sub-
stituents.
observed upon incorporation of an alkyl group at the al-
lene terminus (Scheme 1). In such cases, the intermediate
C2–C6 diradical abstracts a Ca hydrogen to give a formal
ene product.
Key words: ene reactions, allenes, alkynes, radical reactions, ring
closure, kinetic isotope effects
‡
R1
H
H
A major concern in chemistry is the elucidation of the pre-
cise mechanism for a given chemical reaction. Two main
categories of mechanism are addressed within classical
physical organic chemistry: concerted and stepwise. By
using experimental techniques such as kinetic isotope ef-
fect (KIE) studies, trapping experiments, stereospecific
labeling, and spectroscopic observations,1 in conjunction
with theoretical studies, many mechanisms have been
classified as either concerted or stepwise. Even two de-
cades ago, however, Carpenter emphasized that the com-
plexity of a reaction mechanism may depend on the
significance and contribution of nonstatistical dynamic
effects.2 In particular, when molecules with a large excess
of kinetic energy pass through an intermediate that lies in
a shallow energy well, they may fail to undergo vibration-
al energy redistribution and may proceed along a vibra-
tional mode that is mainly determined in the preceding
transition state to form products directly. In such cases,
the overall reaction mechanism will appear to be a con-
certed process in terms of the nature of its products and
stereoselectivity, despite the existence of an intermediate
on the potential-energy surface.3 Several reactions involv-
ing diradical intermediates show this type of behavior.
path 1
R2
7
R3
R1
R1
6
R2
H
5
4
H
α
R2
1
R3
2
R3
R1
3
BF
EA
H
H
R2
path 2
R3
Scheme 1 Possible reaction mechanisms for the thermal C2–C6/ene
cyclization of enyne–allenes (EA); concerted route (path 1) versus
stepwise route (path 2).
Depending on the substituents at the alkyne and allene ter-
mini, the mechanistic course of the C2–C6/ene cyclization
may change, and different products will be formed. On the
basis of calculations at the (U)B3LYP/6-31G(d) level,
Engels10 predicted that the attachment of a phenyl group
to the alkyne (C7) terminus results in a stepwise reaction
mechanism, whereas a concerted process is more favored
when a hydrogen or a tert-butyl group is present. Recent
results have led to a broader generalization: an aryl group
(or any other radical-stabilizing group) at either the allene
or alkyne terminus should steer the reaction toward a step-
wise mechanism involving a diradical intermediate. Con-
vincing support for this mechanism has only been
SYNTHESIS 2010, No. 13, pp 2213–2222
x
x.
x
x
.
2
0
1
0
Advanced online publication: 27.05.2010
DOI: 10.1055/s-0029-1218799; Art ID: C02710SS
© Georg Thieme Verlag Stuttgart · New York

2214
C. Vavilala et al.
PAPER
established for aryl substitution at the allene terminus contributions from nonstatistical dynamic effects. Further
(with a triisopropylsilyl group at the alkyne locus and a 4- changes in the substituents at key positions of the enyne–
methoxyphenyl group at the allene terminus) in an inter- allene should lead to formal ene reactions in which dy-
molecular KIE study.11
namic or classic mechanistic scenarios would operate. In
an attempt to understand these substituent effects more
thoroughly, we examined the effects of the presence of
aryl substituents at the alkyne terminus and at both the
alkyne and allene loci. The results of intramolecular KIE
studies and of radical-trapping experiments presented
herein show that the choice of an appropriate substituent
triggers either classical or dynamic behavior of enyne–
allenes in thermal cyclization reactions.
However, the mechanistic situation is much more com-
plex than merely a dichotomy between a concerted and a
stepwise reaction. The C2–C6/ene cyclization of an
enyne–allene lacking any radical-stabilizing substituents
was examined by Singleton and Lipton through studies on
the intermolecular KIE, as well as by theoretical and dy-
namic calculations of trajectories.12 The observed KIE of
1.43 agreed well with the theoretically predicted value of
1.54 for a concerted ene process. For the parent enyne–al- For our studies on benzannulated enyne–allenes with a
lene EA (R1 = Me; R2 = R3 = H), which lacks benzannu- phenyl group at the alkyne terminus, we chose the allenes
lation, the authors could locate only one transition state at EA2–4, which carry bulky, non-radical-stabilizing groups
the (U)B3LYP/6-31G(d,p) level that corresponded to the (such as trimethylsilyl, triisopropylsilyl, or diphenylphos-
concerted process. In dynamic trajectory simulations phoryl) at the allene terminus and a 1-deuteriobut-1-yl or
starting from this transition state, many of the trajectories a diphenylcyclopropyl group for mechanistic inspection.
led to the diradical intermediate (28 out of 101), while the To study the effects of radical-stabilizing groups at both
remainder took the concerted route. As a consequence, the allene and alkyne termini, we selected the enyne–
Singleton and Lipton postulated that both the stepwise and allenes EA5–7, which have a phenyl or a 4-tolyl group at
concerted ene reaction of enyne–allenes proceed via a sin- the alkyne locus and a mesityl or a 3-tolyl group at the
gle transition state, and that dynamic effects at a post- allene terminus. Again, a 1-deuteriobut-1-yl group was
transition-state valley–ridge inflection point decide chosen for evaluation of the intramolecular KIE.
whether concerted or stepwise trajectories are adopted.
The synthesis of EA2 and EA3 began with Sonogashira
This theoretical study received strong experimental con- cross-coupling of 2-iodobenzaldehyde with phenylacety-
formation from our recent studies on the KIEs in the C2– lene to give the aldehyde 1a.15 Addition of a Grignard re-
C6/ene cyclization of various enyne–allenes substituted at agent RC≡CMgBr (R = TMS, TIPS) (Scheme 3) gave the
the alkyne terminus with tert-butyl, trimethylsilyl, or tri- corresponding propargylic alcohols 2a and 2b.16 Subse-
isopropylsilyl groups and at the allene terminus with 4- quent reaction with acetic anhydride at room temperature
methoxyphenyl or trimethylsilyl groups,13 as the observed in the presence of 4-(N,N-dimethylamino)pyridine
inter- and intramolecular KIEs clearly deviated from the (DMAP) gave the corresponding propargyl acetate 3a or
statistical ratios. When a radical-stabilizing substituent, 3b.17 Enyne–allenes EA2 and EA3 were finally obtained
such as 4-methoxyphenyl, was present at the allene termi- by means of the copper(I) iodide/lithium bromide-pro-
nus, the stepwise mechanism was more pronounced than moted reaction18 of bromo(butyl)magnesium-d1 with 3a
the concerted one. In the absence of a radical-stabilizing or 3b at 0 °C. 1H and 13C NMR and IR spectroscopy and
group, however, the concerted mechanism was more fa- high-resolution MS confirmed the structural assignment
vored. The results from the kinetic isotope study were also of EA2 and EA3.
consistent with recent radical clock experiments.14 In the
case of allene EA1 (Scheme 2), which has an aryl group
Ph
Ph
at the allene terminus, trapping of the diradical intermedi-
ate was readily accomplished by using an ultrafast diphe-
nylcyclopropyl radical clock, whereas slower radical
clocks, e.g. cyclopropyl or phenylcyclopropyl groups, did
not permit trapping of the diradical intermediate.14
ii)
i)
R
H
OH
O
2a: R = TMS
2b: R = TIPS
1a
The results of all mechanistic studies conducted until now
reveal a complex picture for the C2–C6/ene cyclization,
pointing to a common transition state12,13 for both step-
wise and concerted processes, and showing important
Ph
Ph
H
R
R
ii)
D
O
Ph
TIPS
TIPS
Ph
O
Ph
Ph
EA2: R = TMS
EA3: R = TIPS
3a: R = TMS
3b: R = TIPS
heat
Ar
Ar
Scheme 3 Synthesis of enyne–allenes EA2 and EA3. Reagents and
conditions: (i) EtMgBr, HC≡CR, THF, r.t., 8 h, 2a: 88%, 2b: 92%; (ii)
Ac2O, DMAP, Et3N, r.t., 1 h, 3a: 91%, 3b: 80%; (iii) PrCHDMgBr,
CuI/LiBr, 0 °C, 2 h, EA2: 74%, EA3: 47%.
H
EA1
BF1
Ar = 4-(4-BrC6H4)2NC6H4
Scheme 2 Thermal ring opening of the allene EA114
Synthesis 2010, No. 13, 2213–2222 © Thieme Stuttgart · New York

PAPER
C2–C6/Ene Cyclization of Enyne–Allenes
2215
Ph
Ph
Ph
(i)
Ph
(ii)
Ph
Ph
Ph
H
P(O)Ph2
H
OH
O
1a
4
EA4
Scheme 4 Synthesis of EA4. Reagents and conditions: (i) EtMgBr, 1,1¢-(2-ethynylcyclopropane-1,1-diyl)dibenzene, THF, r.t., 8 h, 4: 89%;
(ii) ClPPh2, Et3N, THF, –40 °C to r.t., 3 h, EA4: 47%.
EA4 was obtained in three steps from 1a. Addition of the HB of BF in the 1H NMR (400 MHz) spectrum
Grignard reagent prepared by the reaction of bromo(eth- (Scheme 6). Two to four independent experiments were
yl)magnesium with 1,1¢-(2-ethynylcyclopropane-1,1- performed to establish the values from the KIEs (this
diyl)dibenzene and subsequent reaction with chlo- number is reported as n in Tables 1– 3).
ro(diphenyl)phosphine6d gave the required enyne–allene
Table 1 Experimental Intramolecular KIEs in the Thermal C2–C6/
ene Cyclization of EA2 and EA3
EA4 in 47% yield (Scheme 4).
Enyne–allenes EA5–7 were synthesized analogously to
Compound
EA2
Temp (°C)
100
Intramolecular KIE (n)
1.002 0.001 (3)
EA2 and EA3 by the copper(I) iodide/lithium bromide
protocol (Scheme 5).
R1
R1
EA3
100
1.003 0.001 (3)
ii)
i)
R2
Furthermore, the intramolecular KIE for EA2 was found
to be near unity over a wide range of temperatures
(Table 2).
H
OH
O
1a: R1 = Ph
5a: R1 = Ph, R2 = Mes
5b: R1 = 4-Tol, R2 = Mes
5c: R1 = 4-Tol, R2 = 3-Tol
Table 2 Temperature Effects on the Intramolecular KIE for the
Thermal Ene Reaction of EA2
1b: R1 = 4-Tol
Entry
Temp (°C)
80
Intramolecular KIE (n)
1.002 0.001 (2)
1.002 0.001 (3)
1.003 0.001 (2)
1.002 0.001 (2)
R1
R1
1
2
3
4
H
iii)
D
R2
100
R2
120
O
O
150
6a: R1 = Ph, R2 = Mes
6b: R1 = 4-Tol, R2 = Mes
6c: R1 = 4-Tol, R2 = 3-Tol
EA5: R1 = Ph, R2 = Mes
EA6: R1 = 4-Tol, R2 = Mes
EA7: R1 = 4-Tol, R2 = 3-Tol
For EA5, EA6, and EA7, the observed intramolecular
KIEs are shown in Table 3. Those of EA5 and EA7 were
measured at various temperatures and showed the typical
trend of lower KIEs at higher temperatures.
Scheme 5 Synthesis of enyne–allenes EA5–7. Reagents and condi-
tions: (i) EtMgBr, HC≡CR2, THF, 8 h, 5a: 83%, 5b: 79%, 5c: 79%;
(ii) Ac2O, DMAP, Et3N, 1 h, 6a: 85%, 6b: 80%, 6c: 84%; (iii) PrCH-
DMgBr, CuI/LiBr, 0 °C, 2 h, EA5: 68%, EA6: 57%, EA7: 57%.
Thermal cyclization of EA4 in toluene at 110 °C gave the
cyclopropyl ring-opened product BF4 in 40% yield
(Scheme 7).
The structure of BF4 was assigned on the basis of 1H and
13C NMR spectroscopy and high-resolution mass spec-
troscopy, and established unambiguously by means of X-
ray crystal structure analysis (Figure 1).
Thermolysis of enyne–allenes EA2 and EA3 in toluene
furnished the formal ene products BF2 and BF3, respec-
tively, in good yields.
The intramolecular KIE (Table 1) was determined from
the relative integration of the olefinic hydrogens HA and
R1
R1
R1
D
HB
HA
D
H
R2
R2
D
R2
R3
heat
+
R3
R3
EA-d1
BF-d1 (HA)
BF-d1 (HB)
Scheme 6 Measurement of the intramolecular KIE from the product ratio BF-d1 (HA)/BF-d1 (HB)
Synthesis 2010, No. 13, 2213–2222 © Thieme Stuttgart · New York

2216
C. Vavilala et al.
PAPER
2.48 Å, and a weak intermolecular C-H···p-phenyl inter-
Table 3 Observed Intramolecular KIEs for EA5–7
action.
Compound
EA5
Temp (°C)
Intramolecular KIE (n)
1.739 0.004 (2)
1.551 0.003 (4)
1.543 0.003 (2)
1.581 0.004 (4)
1.339 0.006 (4)
The structures of all the model compounds used in the
study are summarized in Figure 2.
60
80
80
50
60
EA5
Enyne–allenes
(a) without radical-stabilizing substituents
EA6
R
H
EA7
D
Pr
EA7
TMS
H
Ph
Ph
Ph
Ph
Ph
EA8: R = TMS
EA9: R = t-Bu
EA12
toluene
110 °C
Ph
P(O)Ph2
P(O)Ph2
H
(b) with aryl substituents at the allene terminus
EA4
BF4
R
D
TIPS
Ph
Scheme 7 Thermolysis of EA4
H
Pr
Ph
Ar
C6H4(4-OMe)
Ar = 4-(4-BrC6H4)2NC6H4
EA10: R = TIPS
EA11: R = TMS
EA1
(c) with aryl substituents at the alkyne terminus
Ph
Ph
H
D
Ph
Pr
Ph
P(O)Ph2
R
EA2: R = TMS
EA3: R = TIPS
EA4
(d) with aryl substituents at both the allene and alkyne termini
R1
H
D
Figure 1 Crystal structure of BF4
The indene group is approximately planar, and the mean
deviation of the C atoms from the best plane is 0.012 Å.
The angle between the plane of the indene group and the
plane of the phenyl ring (labeled C12 through C17) is
61.7°. The P–O bond is coplanar with the C1–C18 double
bond [torsion angle O1–P1–C1–C18 = 0.6(1)°], resulting
in a short intramolecular contact distance of 2.47 Å be-
tween O1 and H18A. There is a short intramolecular C–
H···p contact between the C11–H11A bond and atom C1
(distance H11A···C1 = 2.59 Å). Very similar intramolec-
ular contacts are found in a related compound.6d The C1–
C18 and C19–C20 double bonds are coplanar [torsion an-
gle C1–C18–C19–C20 = 178.8(1)°]. The angle between
the planes of the phenyl groups attached to phosphorous
atom P1 is 58.1°. The angles between the plane of the
C19–C20 double bond and the planes of the phenyl
groups attached to C20 are 44.0 and 50.1°, respectively,
and the angle between the planes of these phenyl groups
is 76.7°. The crystal packing shows two short intermolec-
ular C–H···O contacts with H···O distances of 2.44 and
R2
EA5: R1 = Ph, R2 = Mes
EA6: R1 = 4-Tol, R2 = Mes
EA7: R1 = 4-Tol, R2 = 3-Tol
Figure 2 A full list of model compounds
The present results complement data obtained with
enyne–allenes EA8–EA11, which have been presented in
a short communication,13 and now provide a fully consis-
tent picture regarding the mode of the C2–C6/ene reaction.
For a comprehensive analysis, we differentiate between
four different groups of compounds: (a) enyne–allenes
without radical-stabilizing substituents; (b) enyne–allenes
with aryl groups at the alkyne unit; (c) enyne–allenes with
aryl groups at the allene terminus; and (d) enyne–allenes
with aryl groups at both the allene and alkyne termini. In
Table 4, collected data from the present study and an ear-
lier study13 are presented in full, allowing us to address all
the cases (a)–(d) systematically.
Synthesis 2010, No. 13, 2213–2222 © Thieme Stuttgart · New York

PAPER
C2–C6/Ene Cyclization of Enyne–Allenes
2217
Table 4 Summary of KIEs and Other Properties of EA1–12
Category
Compound Intermolecular KIE Intramolecular KIE Remarks
Prevailing character
(d0/d2)
(d1)
of mechanism
(a) No radical-stabilizing substituent
EA8
1.60a
1.352a
1.57a,c
1.286a
KIE temp. dependent
concerted
EA12
EA9
1.61a,b
1.24a
concerted
boundary
EA1
ring opense,f
stepwise + dynamic
stepwise + dynamic
(b) Aryl substituent at the allene
terminus
EA10
EA11
EA2
1.17d
1.08a
1.003a
1.001a
1.002g
1.003g
KIE temp. independent stepwise + dynamic
KIE temp. independent stepwise + dynamic
stepwise + dynamic
(c) Aryl substituent at alkyne terminus EA3
EA4
EA5
ring opensf,g
stepwise + dynamic
stepwise + dynamic
stepwise + dynamic
stepwise + dynamic
1.55g
1.54g
1.34g
KIE temp. dependent
(d) Aryl groups at both the allene and EA6
alkyne loci
EA7
KIE temp. dependent
a Ref. 13.
b kCH3/kCD3
.
c kCH3/kCH2D
d Ref. 11.
e Ref. 14.
.
f Diphenylcyclopropyl ring opens in the thermolysis.
g This work.
With regard to group (a) enyne–allenes without any radi- constant over a wide range of temperatures (80–150 °C
cal stabilizing substituents, EA8 and EA9, as described in for EA10).13 The near-unity intramolecular KIE and its
a previous communication,13 are typical of enyne–allenes temperature independence can only be explained reason-
that lack any radical-stabilizing subunit. Their experimen- ably in terms of Carpenter’s dynamic model.2 Carpenter
tal intra- and intermolecular KIEs in the C2–C6/ene reac- argued that, in cases such as this, an intermediate will not
tion are significantly greater than one. In addition, the explore the local minimum through statistical kinetic be-
observed intramolecular KIEs deviate from the corre- havior. Instead, the intermediate is formed with such an
sponding intermolecular KIEs more than can be explained excess of kinetic energy that it overcomes the barrier for
in terms of secondary isotope effects. We interpreted13 the the second step in a nonstatistical dynamic mode to col-
difference between inter- and intramolecular KIEs as rep- lapse directly to the product.3 This assumption is substan-
resenting a mixing of stepwise and concerted trajectories, tiated by the low computed value of the barrier for
with contributions from the former predominating.
hydrogen transfer from C1 to C7 of 1.8 kcal mol–1, and a
value of the energy difference between the preceding tran-
sition state TS1 and the diradical of about 18 kcal mol–1.13
These reaction features provide the impetus for conserva-
tion-of-momentum, nonstatistical, dynamic behavior in
the conversion of the diradical into the ene products. As a
result, in experiments we detected a complete lack of dis-
crimination between hydrogen and deuterium in the in-
tramolecular abstraction process. To provide a rational
explanation of why the intramolecular KIE is greater than
1.005, the trajectories must be exclusively stepwise, be-
cause the mixing in of even small amounts of concerted
trajectories would raise the value of the KIE significantly
above one.
The intra- and intermolecular KIEs for EA10 and EA11,
each of which has an aryl group at the allene terminus,
have previously been studied as representatives of group
(b).13 For both systems, the observed values of the inter-
molecular KIEs are close to one, but not within the ex-
pected range for a classical interpretation of a stepwise
process (i.e., 1.00–1.05).19 Extensive computational re-
sults for the parent system EA1212,13 led us to assume that
there is a single transition state for both the concerted and
stepwise processes for both EA10 and EA11. Indeed, the
somewhat elevated intermolecular KIEs of 1.08–1.17
suggest that the transition states for EA10 and EA11 in-
volve contributions from both the concerted (roughly 10–
20%) and stepwise (80–90%) mechanisms.
For group (c), as judged by the experimental KIEs and
radical clock reactivity, the presence of an aryl group at
the alkyne terminus appears to have the same effect as one
at the allene terminus. For example, for enyne–allenes
Importantly, the observed values of the intramolecular
KIEs for EA10 and EA11 were both one, and they were
Synthesis 2010, No. 13, 2213–2222 © Thieme Stuttgart · New York

2218
C. Vavilala et al.
PAPER
EA2 and EA3, the observed values of the intramolecular cal minima, in agreement with conventional view that rad-
KIEs were very close to one (EA2: 1.002; EA3: 1.003) ical-stabilizing (aryl) groups at both the alkyne and allene
and, in the case of EA2, the KIE was constant over a wide termini markedly stabilize the resulting diradical, leading
range of temperatures (80–150 °C). The C2–C6/ene reac- to a higher barrier for any subsequent reactions. As a re-
tion of enyne–allenes belonging to group (c) therefore sult of intramolecular redistribution of the vibrational en-
proceeds by a stepwise mechanism; this hypothesis is sup- ergy in the diradical, its subsequent reactions will be
ported by the radical clock results for EA4. In the case of subject to classical statistical kinetics, leading to discrim-
this compound, which is substituted with an aryl group at ination between the abstraction of hydrogen and that of
the alkyne terminus, we were able to trap the diradical in- deuterium.
termediate intramolecularly through the ultrafast diphe-
The C2–C6/ene reaction of enyne–allenes emerges as a
nylcyclopropyl radical clock reaction. As the
unique case of mechanistic diversity, at the borderline be-
intramolecular trapping did not work with the slower phe-
tween nonstatistical dynamic and classical behavior
(Table 4).
nylcyclopropyl clock (as in the case of EA4¢),6a hydrogen
transfer in the C2–C6/ene mode of EA4¢ must be faster
Depending on the substituent pattern at the enyne–allene,
than the ring-opening reaction (Scheme 8).
various reaction scenarios may apply, as judged purely on
experimental criteria. For enyne–allenes with no radical-
For the model system EA12, the barrier to hydrogen trans-
fer in the diradical to give the ene product was computed
stabilizing substituents [group (a)], a mechanism seems to
to be ~2 kcal mol–1, which has to be compared with the
apply that is mainly described as concerted; however, the
higher barrier for phenylcyclopropyl ring opening of ~6
discrepancy between the inter- and intramolecular KIEs at
kcal mol–1.6a In contrast, the barrier for diphenylcyclopro-
a given temperature indicates that a sizeable proportion
pyl ring opening of about 1–3 kcal mol–1 allows this reac-
(~20%) of the trajectories pass through the diradical inter-
tion to compete with hydrogen transfer.20 Thus, the
mediate.13 For enyne–allenes with one radical-stabilizing
experimental results for EA4 and EA4¢ are well in line
substituent at either the allene terminus or the alkyne ter-
with the computed barriers. Interestingly, we were able to
minus [groups (b) and (c)], the mechanism is clearly step-
trap the diradical by using the diphenylcyclopropyl unit
wise, as judged by the values of the intramolecular KIEs,
which are near unity. Both, the values of the intramolecu-
lar KIEs and their temperature independence clearly show
even though there is no isotopic discrimination in EA2
and EA3, as can be seen from the corresponding intramo-
lecular KIEs. How is it possible to rationalize the compe-
that the subsequent hydrogen abstraction in the intermedi-
tition between ring opening and hydrogen transfer, when
ate diradical is controlled by nonstatistical dynamics. In-
the latter is classified as a nonstatistical dynamic process?
directly, the radical clock ring openings for enyne–allenes
One possible explanation is that the C–C bond cleavage of
in groups (b) and (c) suggest that such processes may also
the cyclopropyl ring occurs as a nonstatistical dynamic
be subject to dynamic effects. Finally, for enyne–allenes
process that is promoted by conformational bias in the
with radical-stabilizing substituents at both the allene and
diradical intermediate. The adoption of an appropriate
alkyne termini [group (d)], the mechanism is clearly step-
conformation to allow opening of the diphenylcyclopro-
wise and follows predominantly a classical statistical ba-
pyl ring prevents the nonstatistical dynamic hydrogen
sis, as shown by the value and the temperature
transfer. On the basis of these considerations, we suggest
dependence of the intramolecular KIEs.
that radical clocks do not necessarily probe intermediate
The present study clearly showed that reactions such as
radical species, but that they might also be subject to non-
the thermal C2–C6/ene reaction of enyne–allenes cannot
statistical dynamic processes.
be fully understood on the basis of conventional statistical
The group (d) enyne–allenes EA5, EA6, and EA7, which
have aryl groups at both alkyne and allene termini showed
intramolecular KIEs that clearly deviated from unity
(Tables 3 and 4). Both, the size of the intramolecular KIEs
and their notable temperature dependence point to classi-
cal behavior of the diradicals in the hydrogen-abstraction
step. It appears, therefore, that thermolysis of EA5–7
leads to diradicals that vibrationally equilibrate at their lo-
approaches to reaction mechanisms. Instead, the C2–C6/
ene process has an intricate mechanism that lies at the in-
tersection between concerted and stepwise processes and
at the border between nonstatistical dynamics and classic
statistical kinetic behavior. An interesting corollary of the
present study is that radical clock openings can compete
with nonstatistical dynamic hydrogen-abstraction pro-
Ph
Ph
Ph
Ph
H
H
R
R
Ph
heat
heat
Ph
P(O)Ph2
R = Ph
R = H
P(O)Ph2
P(O)Ph2
H
EA4 (R = Ph)
EA4' (R = H)
Scheme 8 The faster diphenylcyclopropyl radical clock opens, whereas the phenylcyclopropyl radical clock remains closed in the thermal
reaction of enyne–allenes
Synthesis 2010, No. 13, 2213–2222 © Thieme Stuttgart · New York

PAPER
C2–C6/Ene Cyclization of Enyne–Allenes
2219
was extracted with CH2Cl2 (2 × 25 mL). The combined organic lay-
ers were washed with H2O and brine, then dried (Na2SO4) and con-
centrated under reduced pressure. The residue was purified by
column chromatography [silica gel, hexane–Et2O (98:2)] to give a
colorless oil; yield: 518 mg (91%); Rf = 0.51.
cesses. Although additional theoretical studies are re-
quired, this finding may point to the occurrence of
nonstatistical dynamic radical clock ring openings.
NMR spectra were recorded on a Bruker AC 400 spectrometer.
Chemical shift values are reported in d (ppm) versus TMS. IR spec-
tra were recorded on a Perkin-Elmer 1750 FT-IR spectrometer. An-
hyd THF and Et2O were distilled over Na/benzophenone. CH2Cl2
and Et3N were freshly distilled from CaH under N2. Anhyd toluene
was distilled from K. Commercial reagents were used as received.
Analytical TLC was carried out on Merck silica gel 60 F254 plates.
Column chromatography was performed on Merck silica gel 63–
200 mm. All solvents for column chromatography were distilled be-
fore use. 2-(2-Phenylethynyl)benzaldehyde (1a),15 2-[2-(4-
tolyl)ethynyl]benzaldehyde (1b),6d 3-mesityl-1-{2-[(4-tolyl)ethy-
nyl]phenyl}prop-2-yn-1-ol (5b),21 and 1,1¢-(2-ethynylcyclopro-
pane-1,1-diyl)dibenzene14 were synthesized by using procedures
described in the literature.
IR (film): 2945 (s), 2866 (s), 2230 (w), 2159 (m), 1741 (s), 1494 (s),
1464 (m), 1370 (s), 1238 (s), 1227 (s), 1042 (m), 957 (s), 920 (w),
883 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 0.23 (s, 9 H), 2.10 (s, 3 H), 7.01
(s, 1 H), 7.33–7.39 (m, 5 H), 7.58–7.61 (m, 3 H), 7.75 (d, J = 7.5 Hz,
1 H).
13C NMR (100 MHz, CDCl3): d = 0.30, 20.8, 64.2, 86.1, 92.6, 95.0,
100.8, 122.7, 122.8, 127.9, 128.3, 128.5 (2C), 128.8, 131.6, 132.2,
137.8, 169.4.
HRMS (EI): m/z calcd for C22H22O2Si: 346.139; found: 346.139.
1-[2-(Phenylethynyl)phenyl]-3-(triisopropylsilyl)prop-2-yn-1-
yl Acetate (3b)
Yield: 80%.
1-[2-(Phenylethynyl)phenyl]-3-(trimethylsilyl)prop-2-yn-1-ol
(2a);22 Typical Procedure
IR (film): 2943 (s), 2866 (s), 2230 (w), 2157 (w), 1745 (s), 1494 (s),
1463 (m), 1368 (s), 1239 (s), 1227 (s), 1042 (m), 956 (s), 920 (w),
882 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 1.09 (s, 21 H), 2.07 (s, 3 H), 6.97
(s, 1 H), 7.34–7.42 (m, 5 H), 7.56 (m, 3 H), 7.88 (d, J = 7.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 11.1, 18.5, 20.8, 64.5, 86.1, 89.4,
94.9, 102.9, 122.8, 123.0, 128.1, 128.3, 128.5, 128.5, 128.8, 131.7,
132.2, 137.9, 169.5.
A soln of EtMgBr prepared from EtBr (1.32 g, 12.1 mmol) and Mg
turnings (294 mg, 12.1 mmol) in anhyd THF (5 mL) was refluxed
for 30 min and then cooled to r.t. A soln of TMSCCH (1.19 g, 12.1
mmol) in anhyd THF (5 mL) was added, and the mixture was stirred
at r.t. for 4 h. A soln of aldehyde 1a (1.00 g, 4.85 mmol) in anhyd
THF (5 mL) was added and the mixture was again stirred for 4 h at
r.t. The reaction was quenched with sat. aq NH4Cl, and the aqueous
layer was extracted with Et2O (2 × 25 mL). The combined organic
layers were dried (Na2SO4) and concentrated under reduced pres-
sure, and the residue was purified by column chromatography [sili-
ca gel, hexane–Et2O (95:5)] to give a colorless oil; yield: 1.30 g
(88%); Rf = 0.52.
HRMS (EI): m/z calcd for C28H34O2Si: 430.233; found: 430.230.
{1-(1-Deuteriobutyl)-3-[2-(phenylethynyl)phenyl]propa-1,2-
dien-1-yl}(trimethyl)silane (EA2)
A soln of PrCHDMgBr, prepared from Mg (41.0 mg, 1.73 mmol)
and PrCHDBr (241 mg, 1.73 mmol)23 in anhyd THF (10 mL), was
added to a well-stirred mixture of LiBr (298 mg, 3.46 mmol) and
CuI (330 mg, 1.73 mmol) in THF at 0 °C, and the soln was stirred
for 15 min before a soln of propargyl acetate 3a (200 mg, 578 mmol)
in anhyd THF (5 mL) was added dropwise at 0 °C. The mixture was
stirred for 2 h and then the reaction was quenched with sat. aq
NH4Cl. The aqueous layer was extracted with Et2O (2 × 25 mL),
and the combined organic layers were dried (Na2SO4) and concen-
trated under reduced pressure. The residue was purified by column
chromatography (silica gel, pentane) to give a colorless oil; yield:
148 mg (74%); Rf = 0.67.
IR (film): 3540 (m), 2960 (s), 2898 (m), 2172 (m), 1611 (s), 1493
(s), 1250 (s), 1186 (m), 1037 (s), 984 (s), 868 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 0.21 (s, 9 H), 2.85 (d, J = 5.9 Hz,
1 H), 5.96 (d, J = 5.9 Hz, 1 H), 7.33 (td, J = 7.5, 1.3 Hz, 1 H), 7.36–
7.42 (m, 4 H), 7.36–7.42 (m, 3 H), 7.75 (d, J = 7.3 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = –0.25, 63.6, 86.5, 91.3, 94.9,
104.3, 121.4, 122.7, 126.6, 128.2, 128.3, 128.5, 128.8, 131.5, 132.3,
141.9.
HRMS (EI): m/z calcd for C20H20OSi: 304.128; found: 304.128.
1-[2-(Phenylethynyl)phenyl]-3-(triisopropylsilyl)prop-2-yn-1-
ol (2b)
Yield: 92%.
IR (film): 3500 (m), 2954 (s), 1917 (w), 1598 (m), 1493 (s), 1443
(m), 1249 (m), 839 (m), 754 (s) cm–1.
1H NMR (400 MHz, toluene-d8): d = 0.10 (s, 9 H), 0.83 (t, J = 7.4
Hz, 3 H), 1.30 (sext, J = 7.4 Hz, 2 H), 1.40–1.49 (m, 2 H), 1.98–
2.01 (br m, 1 H), 6.49 (d, J = 3.0 Hz, 1 H), 7.16 (td, J = 7.4, 1.3 Hz,
1 H), 7.31 (td, J = 7.4, 1.3 Hz, 1 H), 7.38–7.44 (m, 3 H), 7.48 (dd,
J = 8.0, 0.8 Hz, 1 H), 7.55 (dd, J = 7.7, 1.1 Hz, 1 H), 7.62–7.66 (m,
2 H).
13C NMR (100 MHz, CDCl3): d = –1.29, 13.9, 22.6, 28.8 (CHD),
31.4, 87.9, 88.0, 93.8, 101.0, 119.8, 123.5, 125.2, 125.3, 128.1,
128.3, 128.4, 131.5, 132.3, 138.1, 205.6.
IR (film): 3541 (m), 2960 (s), 2898 (m), 2173 (m), 1611 (s), 1493
(s), 1251 (s), 1189 (m), 1037 (s), 983 (s), 868 (s), 757 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 1.06 (s, 21 H), 2.61 (d, J = 5.1 Hz,
1 H), 5.98 (d, J = 5.1 Hz, 1 H), 7.32–7.39 (m, 5 H), 7.54–7.57 (m, 3
H), 7.75 (d, J = 7.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 11.1, 18.6, 63.7, 86.6, 88.0, 94.8,
106.3, 121.6, 122.8, 126.7, 128.2, 128.3, 128.6, 128.8, 131.6, 132.4,
142.2.
HRMS (EI): m/z calcd for C26H32OSi: 388.222; found: 388.222.
HRMS (EI): m/z calcd for C24H27DSi: 345.202; found: 345.202.
1-[2-(Phenylethynyl)phenyl]-3-(trimethylsilyl)prop-2-yn-1-yl
Acetate (3a); Typical Procedure
A soln of propargyl alcohol 2a (500 mg, 1.64 mmol), DMAP (182
mg, 1.80 mmol), and Et3N (183 mg, 1.80 mmol) in anhyd CH2Cl2
(25 mL) was stirred at r.t. while soln Ac2O (219 mg, 1.80 mmol)
was added dropwise. The mixture was stirred for 1 h at r.t., and then
the reaction was quenched with sat aq NaHCO3. The aqueous layer
{1-(1-Deuteriobutyl)-3-[2-(phenylethynyl)phenyl]propa-1,2-
dien-1-yl}(triisopropyl)silane (EA3)
Yield: 47%.
IR (film): 3478 (w), 2942 (s), 2865 (m), 1915 (w), 1599 (m), 1493
(s), 1462 (m), 1382 (m), 1017 (w), 883 (m), 754 (s) cm–1.
Synthesis 2010, No. 13, 2213–2222 © Thieme Stuttgart · New York

2220
C. Vavilala et al.
PAPER
1H NMR (400 MHz, toluene-d8): d = 0.87 (t, J = 7.4 Hz, 3 H), 1.06–
1.20 (br m, 21 H), 1.36 (sext, J = 7.4 Hz, 2 H), 1.58–1.72 (m, 2 H),
2.06–2.15 (br m, 1 H), 6.85 (dd, J = 7.6, 1.1 Hz, 1 H), 6.95–7.02 (m,
4 H), 7.08 (td, J = 7.6, 1.1 Hz, 1 H), 7.40–7-44 (m, 2 H), 7.46 (dd,
J = 7.8, 0.9 Hz, 1 H), 7.69 (bd, J = 7.8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 15.8, 15.9, 23.0, 23.1, 37.9, 38.0,
63.1, 63.2, 80.4, 80.5, 86.6, 86.7, 87.3, 87.4, 94.4, 94.5, 121.2,
121.3, 126.4, 126.5, 126.7, 126.7, 126.7, 127.2, 127.4, 127.8, 127.9,
128.0, 128.1, 128.1, 128.4, 128.4, 128.4, 128.5, 128.8, 130.1, 130.2,
131.5, 132.1, 132.1, 140.8, 140.8, 142.2, 142.3, 144.6, 144.6.
13C NMR (100 MHz, toluene-d8): d = 11.9, 14.1, 19.0, 23.1, 29.9,
31.5 (CHD), 88.6, 89.4, 94.6, 97.4, 120.8, 124.0, 125.9, 126.1,
128.2, 128.5, 128.6, 131.8, 132.9, 138.4, 207.6.
HRMS (EI): m/z calcd for C32H24O: 424.183; found: 424.181.
({1-(2,2-Diphenylcyclopropyl)-3-[2-(phenylethynyl)phe-
nyl]propa-1,2-dien-1-yl}(diphenyl)phosphine Oxide (EA4)
A soln of Ph2PCl (114 mg, 566 mmol) in anhyd THF (5 mL) was
added dropwise during 15 min to a vigorously stirred soln of prop-
argyl alcohol 4 (200 mg, 471 mmol) and Et3N (57 mg, 566 mmol) in
THF (10 mL) cooled to –40 °C. The suspension was stirred at
–40 °C for another 60 min then allowed to warm slowly to r.t. (2 h).
H2O (20 mL) and EtOAc (20 mL) were added, the organic layer was
separated, and the aqueous layer was extracted with EtOAc (2 × 25
mL). The combined organic layers were dried (Na2SO4), filtered,
and concentrated in vacuo to give a residue that was purified by
chromatography [silica gel, hexane–EtOAc (3:2)]; yield: 134 mg
(47%); Rf = 0.57.
HRMS (EI): m/z calcd for C30H39DSi: 429.296; found: 429.296.
[1-(1-Benzylidene-1H-inden-2-yl)-2-deuteriopent-1-en-1-
yl](trimethyl)silane and (1-{1-[Deuterio(phenyl)methylene]-
1H-inden-2-yl}pent-1-en-1-yl)(trimethyl)silane (BF2; Mixture
of Isotopomers)
A soln of allene EA2 (50.0 mg, 144 mmol) in anhyd toluene (20 mL)
was degassed then heated at 100 °C for 12 h. The solvent was re-
moved under reduced pressure, and the residue was purified by TLC
(silica gel 60 F254, pentane) to give a pale yellow oil; yield: 42 mg
(84%); Rf = 0.59.
IR (film): 2943 (s), 2867 (m), 1606 (m), 1599 (s), 1542 (m), 1462
(m), 1381 (m), 1252 (s), 1097 (m), 1072 (m), 1017 (m), 919 (s), 883
(m), 756 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 0.13 (s, 9 H), 0.89 (t, J = 7.3 Hz,
3 H), 1.42 (sext, J = 7.3 Hz, 2 H), 2.02–2.06 (m, 2 H), 6.15 (t,
J = 6.7 Hz, 0.5 H), 6.35 (s, 1 H), 6.90 (t, J = 7.4 Hz, 1 H), 7.00 (s,
0.5 H), 7.14–7.19 (m, 2 H), 7.34–7.45 (m, 4 H), 7.51–7.53 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = –1.45, 13.9, 22.6, 33.3, 119.8,
122.9, 123.8, 126.3, 126.4, 127.8, 128.0, 128.0, 129.1, 129.1, 133.2,
134.2, 137.0, 137.1, 138.0, 138.2, 140.8, 140.9, 144.4, 144.8, 144.9.
IR (film): 3054 (w), 2987 (s), 2853 (s), 2184 (w), 1936 (m), 1599
(w), 1494 (m), 1429 (s), 1186 (s), 1119 (s), 895 (s), 755 (s), 722 (s),
694 (s) cm–1.
1H NMR (400 MHz, acetone-d6): d = 1.63–1.68 (m, 0.45 H), 1.70–
1.74 (m, 1 H), 1.83 (t, J = 5.6 Hz, 0.55 H), 2.38–2.45 (m, 0.45 H),
2.46–2.55 (m, 0.55 H), 5.40 (d, J = 7.6 Hz, 0.45 H), 5.94 (d,
J = 10.4 Hz, 0.55 H), 6.87 (td, J = 7.7, 1.3 Hz, 0.45 H), 7.06 (dd,
J = 10.8, 2.3 Hz, 0.55 H), 7.12–7.44 (m, 10 H), 7.47–7.74 (m, 15
H), 7.88–7.90 (m, 1 H), 8.03 (ddd, J = 12.0, 7.6, 1.6 Hz, 1 H), 8.12
(ddd, J = 12.0, 7.6, 1.6 Hz, 1 H).
13C NMR (100 MHz, acetone-d6): d = 17.5, 17.5, 19.8, 19.8, 23.2,
23.4, 24.7, 24.8, 40.7, 40.3, 86.6, 86.7, 93.9, 94.1, 95.5, 95.6, 95.8,
95.9, 102.5, 102.8, 103.5, 103.7, 120.1, 120.2, 120.4, 120.4, 122.6,
122.7, 126.0, 126.1, 126.2, 126.4, 126.5, 126.7, 126.7, 126.8, 127.3,
127.6, 127.7, 127.8, 127.9, 128.0, 128.0, 128.4, 128.4, 128.4, 128.5,
128.5, 128.6, 131.2, 131.2, 131.3, 131.3, 131.3, 131.4, 131.5, 131.5,
131.6, 131.8, 131.8, 131.9, 131.9, 132.0, 132.1, 132.2, 132.4, 133.1,
133.1, 133.3, 133.4, 133.9, 133.9, 140.4, 141.7, 146.1, 146.8, 208.6,
208.6 (diastereomers and rotamers).
HRMS (EI): m/z calcd for C24H27DSi: 345.202; found: 345.202.
[1-(1-Benzylidene-1H-inden-2-yl)-2-deuteriopent-1-en-1-
yl](triisopropyl)silane and (1-{1-[Deuterio(phenyl)methylene]-
1H-inden-2-yl}pent-1-en-1-yl)(triisopropyl)silane (BF3; Mix-
ture of Isotopomers)
A soln of allene EA3 (20 mg, 46 mmol) in anhyd toluene (15 mL)
was heated at 100 °C for 12 h. The solvent was removed under re-
duced pressure and the residue was purified TLC (silica gel 60 F254
pentane) to give a pale yellow oil; yield: 17 mg (85%), Rf = 0.59.
,
HRMS (EI): m/z calcd for C44H33OP: 608.227; found: 608.227.
IR (film): 2945 (s), 2866 (m), 1606 (m), 1599 (m), 1542 (m), 1463
(m), 1381 (m), 1096 (m), 909 (s), 883 (m) cm–1.
{(1Z)-1-[(1E)-1-Benzylidene-1H-inden-2-yl]-4,4-diphenylbuta-
1,3-dien-1-yl}(diphenyl)phosphine Oxide (BF4)
Allene EA4 (40 mg, 66 mmol) was dissolved in anhyd toluene (50
mL) and heated at 110 °C for 14 h. The toluene was then removed
under reduced pressure, and the residue was purified by TLC [silica
gel 60 F254, hexane–EtOAc (3:2)] to give a pale yellow amorphous
solid; yield: 16 mg (40%); Rf = 0.34.
1H NMR (400 MHz, CDCl3): d = 0.90 (t, J = 7.4 Hz, 3 H), 1.09–1.15
(m, 18 H), 1.24–1.31 (m, 3 H), 1.40–1.50 (m, 2 H), 2.04–2.15 (m, 2
H), 6.19 (t, J = 6.9 Hz, 0.5 H), 6.39 (s, 1 H), 6.89 (t, J = 7.1 Hz, 1
H), 7.14–7.19 (m, 1 H), 7.28 (s, 0.5 H), 7.39 (t, J = 7.1 Hz, 2 H),
7.45 (t, J = 7.5 Hz, 3 H), 7.50–7.52 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 11.4, 13.8, 18.7, 19.0, 22.6, 33.5,
33.6, 119.8, 123.0, 123.8, 126.4, 126.5, 127.8, 128.0, 128.0, 128.4,
129.1, 129.1, 131.4, 132.9, 133.1, 133.3, 134.1, 137.1, 137.2, 140.9,
141.0, 144.7, 145.5, 147.6.
IR (film): 2959 (s), 2928 (m), 1621 (m), 1509 (w), 1437 (s), 1198
(m), 1139 (m), 1021 (m), 910 (s) cm–1.
1H NMR (400 MHz, toluene-d8): d = 6.70 (td, J = 7.1, 1.9 Hz, 2 H),
6.86–6.93 (m, 7 H), 7.01–7.08 (m, 4 H), 7.16–7.20 (m, 4 H), 7.23
(d, J = 1.6 Hz, 1 H), 7.28–7.34 (m, 3 H), 7.41 (s, 2 H), 7.48 (d,
J = 7.6 Hz, 2 H), 7.56 (d, J = 11.5 Hz, 1 H), 7.61 (d, J = 11.5 Hz, 1
H), 7.85 (dd, J = 10.8, 7.6 Hz, 6 H).
HRMS (EI): m/z calcd for C30H39DSi: 429.296; found: 429.296.
3-(2,2-Diphenylcyclopropyl)-1-[2-(2-phenylethynyl)phe-
nyl]prop-2-yn-1-ol (4; Two Diastereomers)
13C NMR (100 MHz, toluene-d8): d = 121.4, 123.6, 124.6, 124.8,
125.5, 128.3, 128.4, 128.5, 128.5, 128.6, 129.4, 129.5, 129.7, 129.7,
130.8, 131.3, 131.3, 132.4, 132.5, 133.7, 133.8, 134.8, 135.4, 137.2,
137.6, 137.7, 138.0, 138.0, 139.0, 141.2, 141.2, 142.1, 142.9, 143.0,
143.9, 144.0, 150.0.
Procedure as described for the synthesis of 2a; yield: 89%.
IR (film): 3565 (m, OH), 3059 (s), 2987 (s), 2237 (s), 1600(m),
1494 (s), 1446 (m), 1378 (w), 1311 (w), 1270 (m), 1124 (w), 1024
(m), 988 (m), 896 (m), 866 (m) cm–1.
1H NMR (400 MHz, CDCl3): d = 1.62–1.67 (m, 1 H), 1.73 (t,
J = 5.2 Hz, 0.4 H), 1.80 (t, J = 5.2 Hz, 0.6 H), 2.25–2.31 (m, 2 H),
5.81 (s, 1 H), 7.04 (d, J = 7.5 Hz, 0.4 H), 7.12 (d, J = 7.5 Hz, 0.6 H),
7.16–7.30 (m, 10 H), 7.36–7.45 (m, 5 H), 7.48–7.54 (m, 3 H).
HRMS (EI): m/z calcd for C44H33OP: 608.227; found: 608.227.
3-Mesityl-1-[2-(phenylethynyl)phenyl]prop-2-yn-1-ol (5a)
Procedure as described for the synthesis of 2a; yield: 83%.
Synthesis 2010, No. 13, 2213–2222 © Thieme Stuttgart · New York

PAPER
C2–C6/Ene Cyclization of Enyne–Allenes
2221
IR (film): 3419 (m), 3061 (s), 2977 (s), 2856 (s), 2221 (s), 1610 (m),
1494 (s), 1446 (m), 1377 (w), 1311 (w), 1241 (m), 1186 (m), 1027
(s), 968 (m), 853 (m) cm–1.
IR (film): 3027 (s), 2870 (m), 2221 (w), 1741 (s), 1610 (m), 1510
(m), 1483 (s), 1369 (m), 1310 (s), 1214 (s), 1117 (s), 1013 (s), 954
(s), 875 (m) cm–1.
1H NMR (400 MHz, CDCl3): d = 2.27 (s, 3 H), 2.38 (s, 6 H), 2.79
(d, J = 5.0 Hz, 1 H), 6.26 (d, J = 5.0 Hz, 1 H), 6.84 (s, 2 H), 7.32–
7.37 (m, 4 H), 7.41 (td, J = 7.5, 1.2 Hz, 1 H), 7.55–7.58 (m, 2 H),
7.59 (dd, J = 7.6, 1.2 Hz, 1 H), 7.84 (d, J = 7.6 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 21.0, 21.3, 64.0, 84.5, 86.7, 94.9,
95.8, 119.2, 121.4, 122.8, 126.7, 127.5, 128.2, 128.4, 128.6, 128.9,
131.6, 132.5, 137.9, 140.4, 142.8.
1H NMR (400 MHz, CDCl3): d = 1.98 (s, 3 H), 2.18 (s, 3 H), 2.24
(s, 3 H), 7.01–7.09 (m, 5 H), 7.17–7.28 (m, 4 H), 7.36 (d, J = 8.0 Hz,
2 H), 7.46 (dd, J = 7.2, 1.6 Hz, 1 H), 7.77 (dd, J = 7.6, 1.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 20.9, 21.1, 21.5, 64.5, 84.8, 85.6,
87.4, 95.3, 119.7, 121.9, 123.0, 128.0, 128.1, 128.3, 128.8, 129.0,
129.1, 129.6, 131.6, 132.2, 132.5, 137.9, 138.0, 138.7, 169.6.
HRMS (EI): m/z calcd for C27H22O2: 378.162; found: 378.162.
HRMS (EI): m/z calcd for C26H22O: 350.167; found: 350.167.
2-{1-(1-Deuteriobutyl)-3-[2-(phenylethynyl)phenyl]propa-1,2-
dien-1-yl}-1,3,5-trimethylbenzene (EA5)
Procedure as described for the synthesis of EA2; yield: 68%.
3-(3-Tolyl)-1-{2-[(4-tolyl)ethynyl]phenyl}prop-2-yn-1-ol (5c)
Procedure as described for the synthesis of 2a; yield: 79%.
IR (film): 3439 (m), 3030 (s), 2923 (s), 2856 (s), 2215 (s), 1598 (m),
1510 (s), 1484 (s), 1449 (m), 1381 (w), 1241 (m), 1182 (m), 1093
(m), 1032 (s), 972 (s), 882 (s) cm–1.
IR (film): 2956 (s), 2860 (m), 2151 (w), 1943 (m), 1607 (m), 1510
(s), 1444 (m), 1376 (m), 1311 (s), 1247 (s), 1213 (m), 1037 (m), 946
(s), 849 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 2.31 (s, 3 H), 2.39 (s, 3 H), 2.95
(d, J = 5.9 Hz, 1 H), 6.18 (d, J = 5.9 Hz, 1 H), 7.13–7.22 (m, 4 H),
7.27–7.30 (m, 2 H), 7.34 (td, J = 7.5, 1.3 Hz, 1 H), 7.41 (td, J = 7.5,
1.3 Hz, 1 H), 7.50 (d, J = 8.1 Hz, 1 H), 7.59 (dd, J = 7.6, 1.2 Hz, 1
H), 7.81 (dd, J = 7.6, 1.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 21.1, 21.5, 63.8, 86.0, 86.6, 87.9,
95.3, 119.7, 121.6, 122.3, 126.7, 128.1, 128.2, 128.7, 129.1, 129.3,
131.4, 132.3, 137.8, 138.8, 142.2.
1H NMR (400 MHz, benzene-d6): d = 0.83 (t, J = 7.4 Hz, 3 H), 1.31
(sext, J = 7.4 Hz, 2 H), 1.58–1.65 (m, 2 H), 2.15 (s, 3 H), 2.25–2.31
(br m, 1 H), 2.34 (s, 6 H), 6.79 (s, 2 H), 6.87 (td, J = 7.6, 1.2 Hz, 1
H), 6.94–6.98 (m, 3 H), 7.08 (td, J = 7.6, 1.2 Hz, 1 H), 7.32 (d,
J = 3.5 Hz, 1 H), 7.42–7.44 (m, 2 H), 7.52 (dd, J = 7.8, 1.1 Hz, 1
H), 7.83 (br d, J = 7.8 Hz, 1 H).
13C NMR (100 MHz, benzene-d6): d = 14.1, 20.6, 21.0, 23.0, 30.1,
33.7 (CHD), 88.4, 93.4, 94.7, 108.6, 121.7, 123.8, 126.7, 127.1,
128.4, 128.5, 128.7, 128.9, 131.9, 133.0, 134.6, 135.6, 136.4, 137.6,
203.9.
HRMS (EI): m/z calcd for C25H20O: 336.151; found: 336.150.
3-Mesityl-1-[2-(phenylethynyl)phenyl]prop-2-yn-1-yl Acetate
(6a)
Procedure as described for the synthesis of 3a; yield: 85%.
HRMS (EI): m/z calcd for C30H29D: 391.241; found: 391.241.
2-(1-(1-Deuteriobutyl)-3-{2-[(4-tolyl)ethynyl]phenyl}propa-
1,2-dien-1-yl)-1,3,5-trimethylbenzene (EA6)
Procedure as described for the synthesis of EA2; yield: 57%.
IR (film): 2977 (s), 2856 (m), 2223 (w), 1739 (s), 1609 (m), 1494
(s), 1370 (m), 1336 (w), 1265 (s), 1214 (s), 1014 (s), 909 (s), 855
(m) cm–1.
1H NMR (400 MHz, CDCl3): d = 1.99 (s, 3 H), 2.14 (s, 3 H), 2.29
(s, 6 H), 6.72 (s, 2 H), 7.13 (s, 1 H), 7.20–7.31 (m, 5 H), 7.43–7.48
(m, 3 H), 7.83 (d, J = 7.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 21.0, 21.3, 28.8, 64.9, 85.5, 86.2,
92.6, 95.0, 118.9, 122.8, 122.8, 125.4, 127.5, 128.1, 128.4, 128.5,
128.8, 131.7, 132.3, 138.2, 138.4, 140.6, 169.7.
IR (film): 2956 (s), 2859 (m), 2152 (w), 1943 (m), 1607 (m), 1511
(s), 1444 (m), 1375 (m), 1311 (s), 1247 (s), 1213 (m), 1117 (m),
1037 (m), 946 (s), 850 (s) cm–1.
1H NMR (400 MHz, toluene-d8): d = 0.85 (t, J = 7.4 Hz, 3 H), 1.32
(sext, J = 7.4 Hz, 2 H), 1.57–1.64 (m, 2 H), 2.01 (s, 3 H), 2.15 (s, 3
H), 2.23–2.29 (br m, 1 H), 2.36 (s, 6 H), 6.75 (s, 2 H), 6.79 (d,
J = 8.0 Hz, 2 H), 6.87 (td, J = 7.6, 1.2 Hz, 1 H), 7.07 (td, J = 7.6,
1.2 Hz, 1 H), 7.24 (d, J = 3.5 Hz, 1 H), 7.36 (d, J = 8.0 Hz, 2 H),
7.48 (dd, J = 7.8, 1.1 Hz, 1 H), 7.77 (br d, J = 7.8 Hz, 1 H).
HRMS (EI): m/z calcd for C28H24O2: 392.178; found: 392.178.
13C NMR (100 MHz, toluene-d8): d = 14.1, 19.8, 20.9, 21.2, 23.1,
30.2, 33.7 (CHD), 87.8, 93.5, 94.9, 108.5, 120.9, 121.9, 126.6,
127.0, 128.4, 128.9, 129.1, 129.3, 131.8, 133.0, 134.6, 135.5, 136.3,
138.3, 203.8.
3-Mesityl-1-{2-[(4-tolyl)ethynyl]phenyl}prop-2-yn-1-yl Acetate
(6b)
Procedure as described for the synthesis of 3a, starting from 5b;21
yield: 80%.
HRMS (EI): m/z calcd for C31H31D: 405.257; found: 405.257.
IR (film): 2917 (s), 2851 (m), 2222 (w), 1740 (s), 1610 (m), 1494
(s), 1369 (m), 1336 (w), 1277 (s), 1214 (s), 1013 (s), 954 (s), 911
(s), 855 (m) cm–1.
1H NMR (400 MHz, CDCl3): d = 2.11 (s, 3 H), 2.27 (s, 3 H), 2.38
(s, 3 H), 2.41 (s, 6 H), 6.86 (s, 2 H), 7.17 (d, J = 8.0 Hz, 2 H), 7.23
(s, 1 H), 7.38 (td, J = 7.4, 2.0 Hz, 1 H), 7.42 (td, J = 7.4, 2.0 Hz, 1
H), 7.47 (d, J = 8.0 Hz, 2 H), 7.59 (dd, J = 7.4, 2.0 Hz, 1 H), 7.95
(dd, J = 7.4, 2.0 Hz, 1 H).
1-[4-Deuterio-3-(3-tolyl)hepta-1,2-dien-1-yl]-2-[(4-tolyl)eth-
ynyl]benzene (EA7)
Procedure as described for the synthesis of EA2, yield 57%.
IR (film): 2985 (s), 2864 (m), 2153 (w), 1942 (m), 1607 (m), 1511
(s), 1484 (m), 1450 (s), 1422 (m), 1338 (s), 1311 (s), 1272 (s), 1213
(m), 1141 (m), 1032 (s), 956 (s), 910 (s) cm–1.
1H NMR (400 MHz, Et2O-d10): d = 0.94 (t, J = 7.2 Hz, 3 H), 1.48
(sext, J = 7.2 Hz, 2 H), 1.56–1.70 (m, 2 H), 2.30 (s, 3 H), 2.32 (s, 3
H), 2.48–2.62 (br m, 1 H), 7.00 (d, J = 7.5 Hz, 1 H), 7.11–7.27 (m,
7 H), 7.30 (s, 1 H), 7.42 (d, J = 8.7 Hz, 2 H), 7.50 (d, J = 8.0 Hz, 2
H).
13C NMR (100 MHz, CDCl3): d = 21.0, 21.3, 21.5, 65.0, 85.5, 85.6,
92.6, 95.3, 119.0, 119.8, 123.1, 127.6, 128.1, 128.3, 128.8, 129.1,
131.6, 132.3, 138.2, 138.3, 138.7, 140.7, 169.7.
HRMS (EI): m/z calcd for C29H26O2: 406.193; found: 406.194.
13C NMR (100 MHz, Et2O-d10): d = 13.2, 20.5, 20.6, 22.4, 29.4
(CHD), 29.9, 86.6, 94.1, 95.6, 109.8, 120.4, 121.4, 123.0, 125.9,
126.2, 126.5, 127.5, 127.9, 128.0, 128.7, 131.1, 132.2, 135.7, 135.8,
137.4, 137.8, 207.2.
3-(3-Tolyl)-1-{2-[(4-tolyl)ethynyl]phenyl}prop-2-yn-1-yl Ace-
tate (6c)
Procedure as described for the synthesis of 3a; yield: 84%.
Synthesis 2010, No. 13, 2213–2222 © Thieme Stuttgart · New York

2222
C. Vavilala et al.
PAPER
HRMS (EI): m/z calcd for C29H27D: 377.225; found: 377.225.
Maywald, M. Tetrahedron Lett. 1997, 38, 6177.
(d) Schmittel, M.; Keller, M.; Kiau, S.; Strittmatter, M.
Chem. Eur. J. 1997, 3, 807. (e) Engels, B.; Lennartz, C.;
Hanrath, M.; Schmittel, M.; Strittmatter, M. Angew. Chem.
Int. Ed. 1998, 37, 1960. (f) Schmittel, M.; Strittmatter, M.
Tetrahedron 1998, 54, 13751. (g) Li, H.-B.; Zhang, H.-R.;
Petersen, J. L.; Wang, K. K. J. Org. Chem. 2001, 66, 6662.
(h) Schmittel, M.; Steffen, J.-P.; Maywald, M.; Engels, B.;
Helten, H.; Musch, P. J. Chem. Soc., Perkin Trans. 2 2001,
1331. (i) Yang, Y. H.; Petersen, J. L.; Wang, K. K. J. Org.
Chem. 2003, 68, 5832. (j) Yang, Y. H.; Petersen, J. L.;
Wang, K. K. J. Org. Chem. 2003, 68, 8545.
Crystal data for BF4
C44H33OP, M = 608.67, triclinic, a = 11.568(2), b = 11.872(2),
c = 14.540(2) Å, a = 84.532(13)°, b = 68.391(12)°, g = 66.780(11)°,
V = 1703.3(5) Å3, T = 163(2) K, space group P1 (Nr. 2), Z = 2,
r
calcd = 1.187 g cm–3, m = 0.114 mm–1, reflections collected: 28184,
independent: 9486, R1 = 0.0475, wR2 = 0.1246 [I
> 2s(I)],
GOF = 1.032. Data were recorded with a Siemens SMART 1K
CCD diffractometer with Mo-Ka radiation at 163 K. Structure de-
termination by direct methods.24 H atoms were positioned geomet-
rically and were constrained. Final R(F) = 0.048 for 7513 reflections
with F2 > 2(F2) and R(F) = 0.063 for all 9486 reflections. The full
crystallographic data for compound BF4 have been deposited with
the Cambridge Crystallographic Data Centre as supplementary pub-
lication CCDC 773136; copies can be obtained free of charge on ap-
plication to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax:
+44(1223)336033 or email: deposit@ccdc.cam.ac.uk].
(7) (a) Engels, B.; Hanrath, M. J. Am. Chem. Soc. 1998, 120,
6356. (b) Schreiner, P. R.; Prall, M. J. Am. Chem. Soc. 1999,
121, 8615. (c) Cramer, C. J.; Kormos, B. L.; Seierstad, M.;
Sherer, E. C.; Winget, P. Org. Lett. 2001, 3, 1881.
(d) de Visser, S. P.; Filatov, M.; Shaik, S. Phys. Chem.
Chem. Phys. 2001, 3, 1242. (e) Stahl, F.; Moran, D.;
Schleyer, P. V.; Prall, M.; Schreiner, P. R. J. Org. Chem.
2002, 67, 1453. (f) Schreiner, P. R.; Navarro-Vázquez, A.;
Prall, M. Acc. Chem. Res. 2005, 38, 29.
Acknowledgment
(8) (a) Zhang, H.-R.; Wang, K. K. J. Org. Chem. 1999, 64,
7996. (b) Wang, K. K.; Zhang, H.-R.; Petersen, J. L. J. Org.
Chem. 1999, 64, 1650. (c) Dai, W.-X.; Petersen, J. L.;
Wang, K. K. Org. Lett. 2006, 8, 4665. (d) Zhang, Y.-Z.;
Petersen, J. L.; Wang, K. K. Org. Lett. 2007, 9, 1025.
(9) (a) Schmittel, M.; Kiau, S.; Siebert, T.; Strittmatter, M.
Tetrahedron Lett. 1996, 37, 7691. (b) Schmittel, M.;
Maywald, M.; Strittmatter, M. Synlett 1997, 165.
(10) Musch, P. W.; Engels, B. J. Am. Chem. Soc. 2001, 123,
5557.
We are indebted to the Deutsche Forschungsgemeinschaft (Schm
647/18-1) and to the University of Siegen for financial support of
our work. †C. Vavilala died Feb. 18th, 2010; we are grateful to him
for his friendship and many scientific enlightenments.
References
(1) (a) Carpenter, B. K. Determination of Organic Reaction
Mechanisms; Wiley: New York, 1984. (b) Reactive
Intermediate Chemistry; Moss, R. A.; Platz, M. S.; Jones, M.
Jr., Eds.; Wiley: Hoboken, 2004.
(2) (a) Carpenter, B. K. Acc. Chem. Res. 1992, 25, 520.
(b) Carpenter, B. K. Angew. Chem. Int. Ed. 1998, 37, 3340.
(c) Hrovat, D. A.; Duncan, J. A.; Borden, W. T. J. Am. Chem.
Soc. 1999, 121, 169. (d) Reyes, M. B.; Carpenter, B. K.
J. Am. Chem. Soc. 2000, 122, 10163. (e) Debbert, S. L.;
Carpenter, B. K.; Hrovat, D. A.; Borden, W. T. J. Am. Chem.
Soc. 2002, 124, 7896. (f) Carpenter, B. K. J. Phys. Org.
Chem. 2003, 16, 858.
(11) Schmittel, M.; Vavilala, C. J. Org. Chem. 2005, 70, 4865.
(12) Bekele, T.; Christian, C. F.; Lipton, M. A.; Singleton, D. A.
J. Am. Chem. Soc. 2005, 127, 9216.
(13) Schmittel, M.; Vavilala, C.; Jaquet, R. Angew. Chem. Int.
Ed. 2007, 46, 6911.
(14) Schmittel, M.; Mahajan, A. A.; Bucher, G.; Bats, J. W.
J. Org. Chem. 2007, 72, 2166.
(15) Roensch, K. R.; Larock, R. C. J. Org. Chem. 2002, 67, 86.
(16) Schmittel, M.; Strittmatter, M.; Schenk, W. A.; Hagel, M. Z.
Naturforsch., B 1998, 53, 1015.
(3) For some recent reviews on nonstatistical dynamic effects
with citations to the relevant literature, see: (a) Carpenter,
B. K. In Reactive Intermediate Chemistry; Moss, R. A.;
Platz, M. S.; Jones, M. Jr., Eds.; Wiley-Interscience:
Hoboken / NJ, 2004, 925. (b) Ess, D. H.; Wheeler, S. E.;
Iafe, R. G.; Xu, L.; Çelebi-Ölçüm, N.; Houk, K. N. Angew.
Chem. Int. Ed. 2008, 47, 7592. (c) Yamataka, H. Adv. Phys.
Org. Chem. 2010, 44, 173.
(17) Borzilleri, R. M.; Weinreb, S. M.; Parvez, M. J. Am. Chem.
Soc. 1994, 116, 9789.
(18) Macdonald, T. L.; Reagan, D. R.; Brinkmeyer, R. S. J. Org.
Chem. 1980, 45, 4740.
(19) (a) Starflinger, W.; Kresze, G.; Huss, K. J. Org. Chem. 1986,
51, 37. (b) Orfanopoulos, M.; Foote, C. S. J. Am. Chem. Soc.
1988, 110, 6583. (c) Orfanopoulos, M.; Smonou, I.; Foote,
C. S. J. Am. Chem. Soc. 1990, 112, 3607. (d) Song, Z.;
Beak, P. J. Am. Chem. Soc. 1990, 112, 8126. (e) Adam, W.;
Krebs, O.; Orfanopoulos, M.; Stratakis, M.; Vougioukalakis,
G. C. J. Org. Chem. 2003, 68, 2420.
(20) Guan, X.; Phillips, D. L. THEOCHEM 2007, 811, 135.
(21) Schmittel, M.; Kiau, S. Liebigs Ann./Recl. 1997, 733.
(22) Kawano, T.; Suehiro, M.; Ueda, I. Chem. Lett. 2006, 35, 58.
(23) (a) Ohno, K.; Takagi, Y.; Matsuura, H. J. Phys. Chem. 1993,
97, 5530. (b) Weiske, T.; Schwarz, H. Chem. Ber. 1983,
116, 324.
(4) Schmittel, M.; Strittmatter, M.; Kiau, S. Tetrahedron Lett.
1995, 36, 4975.
(5) (a) Myers, A. G.; Kuo, E. Y.; Finney, N. S. J. Am. Chem.
Soc. 1989, 111, 8057. (b) Nagata, R.; Yamanaka, H.;
Okazaki, E.; Saito, I. Tetrahedron Lett. 1989, 30, 4995.
(6) (a) Schmittel, M.; Strittmatter, M.; Kiau, S. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 1843. (b) Schmittel, M.;
Strittmatter, M.; Vollmann, K.; Kiau, S. Tetrahedron Lett.
1996, 37, 999. (c) Schmittel, M.; Steffen, J. P.; Auer, D.;
(24) Sheldrick, G. M. Acta Crystallogr., Sect. A 2008, 64, 112.
Synthesis 2010, No. 13, 2213–2222 © Thieme Stuttgart · New York