Intramolecular concerted insertion of vinyl cations into C-H bonds: Hydroalkylating cyclization of alkynes with alkyl chloroformates to give cyclopentanes

Article abstract of DOI:10.1002/anie.200504288

(Chemical Equation Presented) Tying the knot: In analogy to singlet carbenes, vinyl cations insert into C-H bonds in a concerted intramolecular reaction, as shown by experimental investigations and quantum mechanical calculations. This reaction is useful for the synthesis of cyclopentane derivatives.

Full text of DOI:10.1002/anie.200504288

Communications
À
C H Insertion
The application of this reaction to alkynes was expected to
give analogously alkylated alkenes. The reaction of 4-octyne
(2a) and 1a under similar reaction conditions in the presence
of Et3Al2Cl3 and with Et3SiH as an additional hydride donor[8]
was expected to proceed via vinyl cation 3a to give 4-
isopropyl-4-octene (4a) (Scheme 2). To our surprise this
DOI: 10.1002/anie.200504288
Intramolecular Concerted Insertion of Vinyl
À
Cations into C H Bonds: Hydroalkylating
Cyclization of Alkynes with Alkyl Chloroformates
To Give Cyclopentanes**
Ursula Biermann, Rainer Koch, and Jürgen O. Metzger*
À
À
C H insertions with formation of a new C C bond are of
topical interest.[1] At present, great efforts are devoted to
[2]
À
developing the transition-metal-catalyzed C H insertion.
The insertion of carbenes into C H bonds proceeds by
direct attack of a nonactivated Csp3 H bond and formation of
À
À
[3]
À
a new C C bond in a concerted one-step reaction.
Theoretical studies[4,5] as well as experimental investigations
in the gas phase[6] have shown that the vinyl cation C2H3+ can
[4,6]
À
insert into the H H bond by formation of the ethyl cation
À
and into the C H bond of methane and of ethane by
formation of the 2-propyl cation[6] and the 2-butyl cation,[5]
respectively.
Recently we reported on the hydroalkylation of alkenes
with alkyl chloroformates induced by ethylaluminum sesqui-
chloride (Et3Al2Cl3).[7] The reaction of the Lewis acid, for
example, with isopropyl chloroformate (1a) gives the isopro-
pyl cation, which adds across the alkene. Transfer of a hydride
ion from an ethylaluminum sesquichloride species to the
adduct carbenium ion takes place by formation of the
hydroalkylation product (Scheme 1).
Scheme 2. Reactions of alkynes 2a–d with 1a in the presence of
Et3Al2Cl3/Et3SiH proceeding via vinyl cations 3a–d. Products 5a,b and
6c,d as well as the side products 4a–d were obtained as mixtures of
diastereomers. Products derived from the exocyclic cyclopentyl cation
8 were not observed.
Scheme 1. Mechanism of the hydroalkylation of alkenes with isopropyl
chloroformate (1a) induced by ethylaluminum sesquichloride.
R=alkyl.
product was formed only as a side product (< 5%). We
isolated 1-isopropyl-2-propylcyclopentane (5a) in 79% yield
as a mixture of two diastereomers in a ratio of 4.6:1. The
analogous reaction of 5-decyne (2b) afforded the 1,2,3-
trialkyl-substituted cyclopentane 5b in 74% yield as a
mixture of four diastereomers in a ratio of 11:6:1:1. In this
case, too, the hydroalkylation product 4b was formed in only
trace amounts (< 2%). The analogous reaction of 3-hexyne
(2c) gave chloroalkene 6c as a diastereomeric mixture (1.3:1)
in 38% yield. The hydroalkylation product 4c was obtained in
about 12% yield. Reaction of 1-octyne (2d) with 1a in the
presence of Et3Al2Cl3 afforded the chloroalkylation product
6d in 40% yield as a diastereomeric mixture and about 5% of
the hydroalkylation product 4d. A cyclopentane derivative or
another cyclic product was not observed in either reaction.
[*] Dr. U. Biermann, Dr. R. Koch, Prof. Dr. J. O. Metzger
Institute of Pure and Applied Chemistry
University of Oldenburg
P.O. Box 2503, 26111 Oldenburg (Germany)
Fax: (+49)441-798-3618
E-mail: juergen.metzger@uni-oldenburg.de
[**] This work was supported financially by the German Research
Foundation (DFG, ME 722/14-1).
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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The formation of products 4–6 can be explained as
on the formation of cyclopentenone derivatives by additions
follows: The initially formed 2-propyl cation adds across the
of acyl cations to alkynes. They discussed a 1,5-hydride shift of
the initially formed acyl vinyl cation followed by an addition–
elimination reaction ADE or alternatively an intramolecular
electrophilic substitution SEi.[11] In our case both mechanistic
alternatives can be excluded with certainty. Cyclopentene
derivatives formed as products of a SEi reaction were not
observed even in trace amounts. The alternative 1,5-hydride
transfer followed by an addition reaction to give a cyclopentyl
cation, which under our reaction conditions could be trapped
by a hydride donor, can be excluded, too, because in this case
the vinyl cation intermediates 3a and 3b should give initially a
primary and secondary alkyl carbenium ion, respectively. Our
investigations of hydroalkylations of alkenes have shown that
1,2-H shifts of the alkyl carbenium ion intermediates are
always faster than all kinds of possible inter- and intra-
molecular trapping reactions.[7] However, products of these
rearranged carbenium ions, such as cyclobutanes, were not
observed. Thus, the 1,5-H shift and the cyclization must
proceed in a concerted reaction (Scheme 4).
À
À
C C triple bond to give vinyl cations 3. If a C H bond is
available in position 5 of 3 an intramolecular 1,5-hydride shift
takes place to give cyclopentyl cations 7a and 7b, respectively,
À
with formation of a new C C bond. Finally, intermolecular
hydride transfer leads to the products 5a and 5b, respec-
tively.[9] The intramolecular 1,5-hydride shift is definitely
faster than the intermolecular hydride transfer from Et3Al2Cl3
or Et3SiH yielding hydroalkylation products 4. In the case of
alkyne 2c a 1,5-hydride shift is not possible. Therefore vinyl
cation 3c is mainly trapped by transfer of a chloride ion from
À
chloroformate 1a or an EtAlCl3 species to give chloroal-
kenes 6c. Apparently the transfer of a chloride ion to the vinyl
cation intermediate is faster than the transfer of a hydride ion.
Marcuzzi and Melloni reported on the chloroalkylation of
alkynes using chloroalkanes in the presence of Lewis acids.[10]
In analogy, the cyclization of vinyl cation 3d should be
possible by formation of the exocyclic carbenium ion 8.
However, products derived from 8 were not observed, giving
evidence that a fast 1,5-hydride shift takes place only if an
endocyclic carbenium ion such as 7a,b is formed. Thus,
alkynes 2c and 2d were treated with 2-butyl chloroformate
(1b) in the presence of Et3Al2Cl3 and Et3SiH. As expected, we
observed the formation of the cyclopentane derivatives 10c
and 10d via vinyl cations 9c and 9d, respectively (Scheme 3).
The diastereomeric mixtures of compounds 10c and 10d were
obtained in yields of 26% (GC) and 13% (GC), respectively.
Interestingly, the reaction of alkyne 2a with alkyl chlorofor-
mate 1b via vinyl cation 9a gave cyclopentane 10a as well as
11 (total yield: 52%) in a ratio of 1:3.
Scheme 4. Concerted intramolecular insertion of vinyl cation 3a into a
À
primary C H bond to give the cyclopentyl carbenium ion 7a.
There are some questions concerning the mechanism of
the formation of the cyclopentanes. Schegolev et al. reported
Our quantum-mechanical calculations (MP2/6-311 + G-
(d,p)//MP2/6-31G(d) + ZPVE)[12] predict that this concerted
À
insertion of vinyl cation 3a into a C H bond is a possible
pathway. After the exothermic formation of 3a
(À197 kJmolÀ1), the reaction proceeds via the transition
state of the concerted process (Figure 1), leading directly to
the cyclopentyl cation 7a. While the latter is stabilized by
about 130 kJmolÀ1 relative to 3a, the activation energy for the
cyclization and simultaneous hydrogen transfer is only
8 kJmolÀ1. The formation of a primary alkyl carbenium ion
À
by 1,5-hydride shift followed by C C bond formation can be
ruled out because the carbenium ion is not a minimum on the
potential energy surface but rearranges by a 1,2-hydrogen
shift to give a secondary alkyl carbenium ion, which cannot
form cyclopentanes. Analysis of the transition stateꢀs single
imaginary frequency reveals a motion of the bond-forming
carbon atoms towards each other, while the hydrogen atom is
moving above the ring system. The relevant distances are in
accordance with those of an insertion of the ethenyl cation
[5]
À
À
into the C H bond of ethane and those of comparable C H
insertion reactions of carbenes.[13–15]
Surprisingly, vinyl cation 3d does not form an exocyclic
secondary cyclopentyl cation 8. The reason could be that the
generation of a secondary cation is energetically less favor-
able than formation of a tertiary endocyclic carbenium ion.
Our calculations with the model vinyl cation 3e (R1 = Pr, R2 =
Bu) demonstrate that the formation of the exocyclic carbe-
nium ion 12 is in particular kinetically disfavored (Scheme 5).
Scheme 3. Reaction of alkynes 2a,c,d with 1b in the presence of
Et3Al2Cl3/Et3SiH proceeding via vinyl cations 9a,c,d to give the
products of a hydroalkylating cyclization 10a,c,d and 11. Cyclopentanes
10a and 11 are formed in a ratio of 1:3 via vinyl cation 9a. The
cyclopentanes were obtained as mixtures of diastereomers. For R1, R2,
see Scheme 2.
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Scheme 5. Model reaction of vinyl cation 3e by endo- and exocyclic
pathways to give the cyclopentyl cations 7e and 12.
À
Keywords: alkylation · alkynes · C H insertion · cyclopentanes ·
vinyl cations
.
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À
À
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vinyl cations 3a,b as well as 9a,c,d should be concerted
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[4–6]
À
insertion of a vinyl cation into C H bonds
in solution, in
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Received: December 2, 2005
Published online: April 5, 2006
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Angewandte
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