Hydrocarbation of C≡C bonds: Quantification of the nucleophilic reactivity of ynamides

Article abstract of DOI:10.1002/anie.201402055

Donor-substituted diarylcarbenium ions Ar₂CH⁺ react with ynamides to give 1-amido-substituted allyl cations (α,β- unsaturated iminium ions). Kinetic studies show that these adducts, which correspond to the addition of a C-H bond across the C≡C bond, are formed stepwise with initial formation of keteniminium ions and subsequent 1,3-hydride shifts. The linear correlations between the second-order rate constants (lgk₂, 20°C) with the electrophilicity parameters E of the diarylcarbenium ions allow us to include ynamides in our comprehensive nucleophilicity scale and thus predict potential electrophilic reaction partners.

Full text of DOI:10.1002/anie.201402055

.
Angewandte
Communications
DOI: 10.1002/anie.201402055
Synthetic Methods
ꢀ
Hydrocarbation of C C Bonds: Quantification of the Nucleophilic
Reactivity of Ynamides**
Hans A. Laub, Gwilherm Evano, and Herbert Mayr*
Dedicated to Professor Klaus T. Wanner on the occasion of his 60th birthday
Abstract: Donor-substituted diarylcarbenium ions Ar2CH+
react with ynamides to give 1-amido-substituted allyl cations
(a,b-unsaturated iminium ions). Kinetic studies show that these
lized benzhydrylium ions and discuss why hydrocarbations of
alkenes and alkynes do not usually take place.
During our investigations of the nucleophilic reactivity of
adducts, which correspond to the addition of a C H bond
ynamides 1a–d[3] (Table 1) by the benzhydrylium method-
ꢁ
ꢀ
across the C C bond, are formed stepwise with initial
formation of keteniminium ions and subsequent 1,3-hydride
shifts. The linear correlations between the second-order rate
constants (lgk2, 208C) with the electrophilicity parameters E of
the diarylcarbenium ions allow us to include ynamides in our
comprehensive nucleophilicity scale and thus predict potential
electrophilic reaction partners.
Table 1: Absorption maxima A and B of the developing a,b-unsaturated
iminium ions during the reactions of benzhydrylium ions 2a–c with
ynamides 1a–d in dichloromethane.
Ynamides
Products from
Products from
Products from
2a
2b
2c
lA [nm] lB [nm] lA [nm] lB [nm] lA [nm] lB [nm]
ꢀ
H
ydroborations[1] of C C and C C bonds belong to the
=
most reliable reactions in organic synthesis (Scheme 1a). As
carbenium ions are isoelectronic with boranes, one might
520
510
513
–
752
736
731
–
474
467
467
–
670
652
650
–
478
472
472
480
670
654
650
649
ology,[4] we observed a color change to green when the blue
benzhydrylium tetrafluoroborate 2c-BF4 (Table 2) was com-
bined with ynamide 1d in CH2Cl2 (Figure 1). UV/Vis
spectroscopic monitoring of this reaction showed that the
green species was formed with the same rate with which the
blue carbenium ion disappeared.
Scheme 1. a) Hydroborations of alkenes compared with b) analogous
hydrocarbations.
wonder why analogous reactions of carbenium ions (Sche-
me 1b) have so far not been reported despite the potential of
such reactions in organic synthesis. We now show that such
reactions occur when ynamides[2] are combined with stabi-
The assumption that the green species is the product of
a hydrocarbation reaction was confirmed by the isolation of
the allylic sulfonamide 4, which was obtained by treatment of
the reaction product 3ab with DIBAL-H (Scheme 2).
As shown in Table 1, the UV/Vis absorption maxima of
the 1-amido-3,3-diarylallyl cations ($a,b-unsaturated imi-
[*] M. Sc. H. A. Laub, Prof. Dr. H. Mayr
Department Chemie, Ludwig-Maximilians-Universitꢀt Mꢁnchen
Butenandtstr. 5–13 (Haus F), 81377 Mꢁnchen (Germany)
E-mail: herbert.mayr@cup.uni-muenchen.de
Table 2: Reference electrophiles used for quantifying the nucleophilic-
ities of 1a–d.
Homepage: http://www.cup.uni-muenchen.de/oc/mayr/
Prof. Dr. G. Evano
Laboratoire de Chimie Organique, Service de Chimie et Physico-
Chimie Organiques, Universitꢂ Libre de Bruxelles
Avenue F. D. Roosevelt 50–CP 160/06, 1050 Brussels (Belgium)
Ar2CH+[a]
R
2
lmax[b] [nm]
E[c]
(dpa)2CH+
(mfa)2CH+
(pfa)2CH+
NPh2
N(CH3)CH2CF3
N(Ph)CH2CF3
2a
2b
2c
672
593
601
ꢁ4.72
ꢁ3.85
ꢁ3.14
[**] We thank the Deutsche Forschungsgemeinschaft (SFB 749, Project
B1) for financial support. Helpful discussions with Dr. J. Bartl, Dr. D.
Stephenson, and Dr. A. R. Ofial are gratefully acknowledged.
[a] dpa=4-(diphenylamino)phenyl; mfa=4-(methyl(trifluoroethyl)ami-
no)phenyl; pfa=4-(phenyl(trifluoroethyl)amino)phenyl. [b] In dichloro-
methane. [c] Empirical electrophilicities E from Ref. [4a].
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201402055.
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Figure 2. Upper part: From the exponential decay of the absorbance of
2c (left) and the exponential increases of the absorbances at 472 nm
(middle) and 654 nm (right) during the reaction of 1b
Figure 1. Time-dependent UV/Vis spectra during the reaction of yna-
mide 1d (c=1.02ꢃ10ꢁ3 m) with benzhydrylium salt 2c-BF4
(c=1.13ꢃ10ꢁ5 m) in dichloromethane at 208C.
(c=4.25ꢃ10ꢁ4 m) with 2c (c=2.17ꢃ10ꢁ5 m) at 208C in CH2Cl2, the
corresponding first-order rate constants kobs (2c), kobs (472 nm), and
kobs (654 nm) were derived. Lower part: The respective second-order
rate constants k2 (2c), k2 (472 nm), and k2 (654 nm) are obtained as
the slopes of the linear correlations of the corresponding first-order
rate constants kobs against [1b]0.
the absorbances of the benzhydrylium ions are directly
related to the rates of the bimolecular reactions, only these
rate constants are given in Table 3.
As depicted in Scheme 3, the formation of 3 may either be
concerted or stepwise with reversible or irreversible forma-
tion of a keteniminium ion 5, which undergoes a subsequent
1,3-hydride shift to give the observed amido allyl cation 3.
This 1,3-hydride shift is not a [1,3]-sigmatropic process,
which is subject to the orbital symmetry rules. Unlike in
a [1,3]-sigmatropic shift, the involved sCH bond is in the plane
of the three carbon atoms, and the Ar2C+-fragment must
rotate to achieve conjugation between the developing carbe-
nium center and the enamide fragment of 3.
Scheme 2. Formation of the allylic sulfonamide 4 by treatment of the
colored intermediate 3ab with DIBAL-H (Ar see Table 2).
nium ions) 3 depend only slightly on the nature of the
substituents at nitrogen and at C-2, but are strongly affected
by the nature of the aryl groups at C-3. The considerably
longer wavelength of the absorption maximum of 2a (com-
pared to 2b and 2c, Table 2) is in line with the bathochromic
shifts of both bands of the allyl cations derived from 2a
compared to those obtained from 2b and 2c (Table 1). The
analogous conjugation of the aryl rings with a carbenium
center in the products 3, as in the benzhydrylium ions 2, is thus
indicated.
When the kinetics of the reactions of the ynamides 1a–d
with the benzhydrylium ions 2a–c were studied under pseudo-
first order conditions ([1a–d] @ [2a–c]), monoexponential
decays of the absorbances of the benzhydrylium ions 2 and
monoexponential increases of both absorbances of the
unsaturated iminium ions 3 were observed, as depicted for
the reaction of 2c with 1b in Figure 2.
Table 3: Second-order rate constants k2 (in mꢁ1 sꢁ1) for the reactions of
the ynamides 1a–d with the benzhydrylium ions 2a–c in dichloro-
methane at 208C.
Ynamides
k2 (2a)
k2 (2b)
k2 (2c)
1a
1b
1c
1d
0.181
0.574
2.48
–
1.07
2.51
12.1
–
3.75
13.1
55.5
0.963
Because some of the iminium ions 3 undergo subsequent
reactions, which are only slightly slower than their formations,
the second-order rate constants derived from the consump-
tion of the benzhydrylium ions 2 and from the formation of
the iminium ions 3 sometimes differ slightly. While Figure 2
shows the coincidence of the different values, Table S1 of the
Supporting Information also includes examples for slight
deviations. As the rate constants derived from the decay of
Scheme 3. Mechanistic alternatives for the reactions of the ynamides
1 with the benzhydrylium ions 2.
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In order to differentiate these mechanistic alternatives, we
have also studied the rate of the reaction of the C-1-
deuterated benzhydrylium ion D-2b (Ar2C-D+) with the
ynamide 1a. As shown in Figure 3, the deuterated benzhy-
1
drylium ion D-2b reacts even faster than its H isotopomer
ꢁ
2b, which excludes breaking of the C H bond in the rate-
determining step.
Figure 4. Plots of lgk2 for the reactions of benzhydrylium ions 2a–c
with ynamides 1a–d in CH2Cl2 at 208C versus the electrophilicity
parameters E of the benzhydrylium ions.
Figure 3. Comparison of the first-order rate constants kobs obtained for
the reactions of benzhydrylium ions (mfa)2CH+ (2b, triangles) and
(mfa)2CD+ (D-2b, circles) with different amounts of ynamide 1a (data
point shown as an open circle was not used for determining k2 (D-
2b)).
The ratio k2(2b)/k2(D-2b) = 0.91 rather corresponds to an
inverse a-secondary kinetic isotope effect, which is typical for
reactions involving rehybridization Csp2 !Csp3 in the rate-
determining step.[5] We thus conclude that the rate constants
listed in Table 3 reflect the attack of the benzhydrylium ions
2a–c at the ynamides 1a–d with irreversible formation of the
keteniminium ions 5. As this step corresponds to the type of
reactions for which Equation (1) was derived, it is now
lg k ð20 ꢂCÞ ¼ sNðN þ EÞ
ð1Þ
possible to determine the nucleophile-specific parameters N
and sN by plotting lgk2 of the rate constants in Table 3 against
the electrophilicity parameters E of the benzhydrylium ions
2a–c (Figure 4).
The linear correlations shown in Figure 4 indicate that all
investigated reactions follow analogous mechanisms. As the
sensitivities sN (slopes of the correlation lines) are similar to
those of related p-nucleophiles,[4g] the nucleophilicity param-
eters N (negative intercepts on the abscissa) can directly be
employed to discuss structure–reactivity relationships.
Figure 5 shows that ynamides 1a–d possess nucleophilic-
ities that are comparable to those of (2-methylallyl)trime-
thylsilane (6)[4a] and butyl vinyl ether (7).[4f] They are
significantly less reactive than enamines,[6] as shown by the
comparison of the structurally related compounds 8b and 1c.
Replacement of the alkyl substituents at the position of
electrophilic attack by a phenyl group decreases the nucleo-
philicities of enamines (8b!8a) as well as of ynamides (1c!
1a) by approximately one order of magnitude. Structurally
related enamides,[7] such as 9, were reported to possess
nucleophilicities of 4.6 < N < 7.1, that is, somewhat higher
than those found for the ynamides 1a–d in this work.
Why do hydrocarbations, as described in Scheme 1b, in
Figure 5. Comparison of the nucleophilicity N of ynamides 1a–d (sN in
parentheses) with those of other p-nucleophiles[4 g] in CH2Cl2 (CH3CN
for enamides; [a] estimated value of sN; [b] nucleophilicity parameter
adjusted to the revised electrophilicity parameters E of the reference
electrophiles given in Ref. [4f]).
bonds in borohydride anions are far better hydride donors
than C H bonds,[8] the zwitterion 12 shown in Scheme 4 is not
ꢁ
formed as an intermediate in hydroboration reactions, as it
would undergo activation-less collapse to the hydroboration
[9]
ꢁ
product (Jencksꢀ criterion ). In contrast, C H bonds are
much poorer hydride donors, and 1,3-hydride migrations in
carbocations are generally slow, even when the hydride
transfer is exothermic.[10] As a consequence, carbocations 13,
which are formed by the addition of a carbocation to an olefin
ꢁ
contrast to hydroborations generally not take place? As B H
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Received: February 3, 2014
Published online: April 8, 2014
Keywords: iminium ions · kinetic isotope effects · kinetics ·
.
linear free energy relationships · vinyl cations
Scheme 4. Comparison of the hypothetical intermediate 12 of a step-
wise hydroboration with the intermediate 13 obtained after the
addition of a carbocation to an alkene.
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(Scheme 1b and 4), are usually trapped by external nucleo-
philes.[11]
For the same reason, Lewis acid catalyzed reactions of
alkyl halides to alkynes give vinyl halides in good yields
(Scheme 5), thus indicating that a hydride transfer in the
intermediate vinyl cation 14 cannot be a major process.[12]
[3] Ynamides 1a–d were synthesized using our previously reported
procedures: a) A. Coste, G. Karthikeyan, F. Couty, G. Evano,
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B. Kempf, R. Loos, A. R. Ofial, G. Remennikov, H. Schimmel, J.
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g) For a comprehensive database of reactivity parameters see
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Scheme 5. Lewis acid catalyzed additions of alkyl halides to alkynes.[12]
A recent report[13] on the formation of benzofurans 15 by
Lewis acid catalyzed reactions of methoxy- and methyl-
substituted or unsubstituted benzhydrols with ynamide 1b
(Scheme 6, pathway a) shows that hydrocarbations through
hydride transfer in the intermediate keteniminium ions 5
(Scheme 6, pathway b), as observed in this work, only occur
when the carbocation generated by hydride transfer is
stabilized by strongly electron-donating groups.
In summary, we have shown that hydrocarbations of
alkynes with carbenium ions are possible when electron-
donating substituents are present in the alkynes and in the
carbenium ions. The observation of an inverse a-secondary
kinetic isotope effect when replacing the hydrogen atom at
C-1 of a carbenium ion with deuterium showed that the
irreversible electrophilic attack of the benzhydrylium ions at
the ynamides is the rate-determining step of the studied
reactions.
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Chem. Soc. 1990, 112, 4446 – 4454.
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Scheme 6. The substitution pattern in the benzhydrylium moiety
determines the subsequent reaction pathway of the keteniminium ion
5.
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