A carbaboranylmercuric salt catalyzed reaction; Highly regioselective cycloisomerization of 1,3-dienes

Article abstract of DOI:10.1021/ol300678r

The combination of carbaboranylmercuric chloride (new type of bulky Lewis acid) and silver triflate efficiently catalyzes cycloisomerization of 1,3-dienes at room temperature. The catalytic system gives allyl-substituted azacycles and cycloalkanes in exce

Full text of DOI:10.1021/ol300678r

ORGANIC
LETTERS
2012
Vol. 14, No. 9
2266–2269
A Carbaboranylmercuric Salt Catalyzed
Reaction; Highly Regioselective
Cycloisomerization of 1,3-Dienes
Hirofumi Yamamoto,* Ikuo Sasaki, Shinya Shiomi, Naoto Yamasaki, and
Hiroshi Imagawa
Faculty of Pharmaceutical Science, Tokushima Bunri University, Yamashiro-cho,
Tokushima 770-8514, Japan
hirofumi@ph.bunri-u.ac.jp
Received March 17, 2012
ABSTRACT
The combination of carbaboranylmercuric chloride (new type of bulky Lewis acid) and silver triflate efficiently catalyzes cycloisomerization of 1,
3-dienes at room temperature. The catalytic system gives allyl-substituted azacycles and cycloalkanes in excellent yields with high to complete
regioselectivity.
Catalytic hydroamination is an atom-ecomomical and
pivotal transformation for the synthesis of organonitrogen
molecules.1 In recent years, especially, the development
of a method for the hydroamination of conjugated dienes
(diene-hydroaminations) has attracted a great deal of
attention2,3 because the olefinic functionality maintained
in the product is useful for subsequent molecular modifica-
tions (such as ozonolysis, hydroboration, metathesis, etc.).
Most recently, Toste and co-workers reported the asym-
metric hydroamination of p-methoxy benzenesulfonyl
(Mbs)-protected amino-1,3-dienes using catalytic amounts
of the (R)-DTBM-SEGPHOS(AuCl)2 complex and
AgBF4 in the presence of (À)-menthol.4 Although high
enantioselectivity as well as good reactivity was observed
with that catalytic system, a regioisomeric mixture of
olefinic moieties was obtained in most cases. The forma-
tion of such untoward regioisomers are no exception in
diene-hydroaminations, and efficient methods which af-
ford a single isomer are still limited. We recently reported
the Hg(OTf)2-catalyzed cyclization of p-toluenesulfonyl
(Ts)-protected amino dienes 1 leading to 2-propenyl aza-
cycles 3 (vinylene-type products) as single E-isomers
(Scheme 1).5 In the hydroaminations, the Hg(OTf)2 acti-
vated the internal olefin of the conjugated diene to regulate
the position of the nascent double bond in the products via
demercuration of the mercuric intermediate 2. Therefore,
€
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r
10.1021/ol300678r
Published on Web 04/19/2012
2012 American Chemical Society

we reasoned that if the terminal olefin moiety could be
preferentially activated using a bulky mercuric reagent
which avoids a crowded internal olefin, the allyl-substi-
tuted 6 (allyl-type product) might be constructed from the
identical 1. Herein, a new method for regioselective synthe-
sis of allyl-substituted compounds from 1,3-dienes is
demonstrated, using a 1:1 combination of a novel carba-
boranylmercuric chloride and AgOTf. The efficient synth-
esis of such allylic compounds using diene-hydroamina-
tion is seldom described in the literature, with the
(CGC)Th(NMe2)2-catalyzed hydroamination reported
by the Marks group being the sole example.6
bulkier reagent to improve the selectivity. Carbaboranes
(C2B10H12),10 in which two of the BHÀ units of the
dodecaborane dianion (B12H122À) are replaced with two
CH vertices, are charge-neutral, stable, and icosahedral-
bulky clusters. Moreover, chemical modification of the
two carbon atoms in the clusters is easy to perform via a
carbanion intermediate (generated by treatment with alkyl
lithium reagents).11 Because of the properties of the mate-
rial, we hypothesized that carbaboranes would be ideal
bulky substituents on the mercury center. While attempts
to catalyze the reaction of 7a using only 5 mol % of
o-carbaborane-linked mercuric chloride 11 did not produce
appreciable amounts of pyrrolidine (entry 7), it was found
that the addition of AgOTf induced production of 8a with
high regioselectivity in very high yield (entry 8). For
m-carbaborane-linked 12, the regioselectivity was increased
further, giving only 8a quantitatively (entry 9). It is parti-
cularly noteworthy that the carbaborane-linked reagents
were highly reactive and that a catalyst loading of 4 mol %
was enough to complete the reaction within a short period
of time (entry 10).
Scheme 1. Hg(OTf)2-Catalyzed Cycloisomerization of 1,3-
Diene 1 and Synthetic Approach to Allyl-Substituted Azacycle
Table 1. Investigation of the Catalysts Leading to 2-Allylpyr-
rolidine 8aa
In the process of developing the Hg(OTf)2-catalyzed
cycloisomerization of 1,3-dienes, we found that a regioi-
someric mixture of 8a and 9a was produced, when 7a was
treated with5 mol %ofPhHgOTf,7 which waspreparedby
in situ mixing of PhHgOAc and HOTf in a 1:1 ratio (Table
1, entry 1).8 Thus, our initial study focused on screening
various combinations9 of phenylmercuric salts and addi-
tives with the aim of achieving the synthesis of allyl-
substituted 8a with high regioselectivity. However, as
shown in entries 2À5, the selective synthesis of 8a is very
difficult, as regioisomeric mixtures were produced in all
cases. A better result was obtained by changing the mer-
curic reagent from phenylmercuric chloride to pentafluor-
ophenylmercuric chloride (10), but the ratio of 8a and 9a
was still 54:46 (entry 6). Therefore, we needed to design a
a Reactions were conducted with 7a (0.1 mmol). b Combined yield of
isolated 8a and 9a. c Determined by 1H NMR spectroscopy. d Determined
by 1H NMR spectroscopy and HPLC analysis. e The starting material 7a
was recovered in >99% yield. f Reactions were conducted with 7a
(5.0 mmol). g The starting material 7a was recovered in 95% yield.
(6) Stubbert, B. D.; Marks, T. J. J. Am. Chem. Soc. 2007, 129, 4253–
4271.
(7) Yamamoto, H.; Sasaki, I.; Hirai, Y.; Namba, K.; Imagawa, H.;
Nishizawa, M. Angew. Chem., Int. Ed. 2009, 48, 1244–1247.
(8) Yamamoto, H.; Sasaki, I.; Shiomi, S.; Imagawa, H. Unpublished
result.
(9) (a) Yamamoto, H.; Sasaki, I.; Namba, K.; Imagawa, H.; Nishizawa,
M. Org. Lett. 2007, 9, 1399–1402. (b) Yamamoto, H.; Sasaki, I.; Mitsutake,
M.; Karasudani, A.; Imagawa, H.; Nishizawa, M. Synlett 2011, 2815–
2818.
(10) (a) Scholz, M.; Hey-Hawkins, E. Chem. Rev. 2011, 111, 7035–
7062. (b) Hawthorne, M. F.; Maderna, A. Chem. Rev. 1999, 99, 3421–
3434.
Org. Lett., Vol. 14, No. 9, 2012
2267

As shown in Scheme 2, m-carbaborane-linked 12, which
showed the best result, can be prepared easily by treatment
of 14 with iodine monochloride (ICI) in CH2Cl2 at 0 °C. The
direct mercuration of m-carbaborane (13) with HgCl2 led to
overreaction, giving dimerized 15 as the major product.12
Table 2. Reaction of 1,3-Dienes 7bÀl with 4 mol % of 12 and
AgOTf (1:1) in CH2Cl2 at Room Temperaturea
Scheme 2. Preparation of m-Carbaboranylmercuric Chloride
The molecular structure13 of 12 was confirmed by an
X-ray diffraction study (Figure 1).14 The CÀHg distance
of 12 is 2.07 A, which is equivalent to that of 11.15 There-
˚
fore, the exact substituent effect of m-carbaborane, which
induces higher regioselectivity than o-carbaborane, is un-
clear. More detailed investigation is required for full
elucidation of the role of the substituent in the activity.
Figure 1. X-ray structure of 12.
Table 2 shows the results for the reactions of a 1:1
combination of 12 and AgOTf with a variety of 1,3-dienes.
(11) (a) Kiran, B.; Anoop, A.; Jemmis, E. D. J. Am. Chem. Soc. 2002,
124, 4402–4407. (b) Jemmis, E. D.; Kiran, B. J. Am. Chem. Soc. 1997,
119, 4076–4077.
(12) (a) Yang, X.; Zheng, Z.; Knobler, C. B.; Hawthome, M. F.
€
J. Am. Chem. Soc. 1993, 115, 193–195. (b) Schoberl, U.; Magnera, T. F.;
Harrison, R. M.; Fleischer, F.; Pflug, J. L.; Schwab, P. F. H.; Meng, X.;
Lipiak, D.; Noll, B. C.; Allured, V. S.; Rudalevige, T.; Lee, S.; Michl, J.
J. Am. Chem. Soc. 1997, 119, 3907–3917.
(13) The single crystal of 12 was obtained from AcOEt at room
temperature.
(14) CCDC 862695 contains the supplementary crystallographic
data. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre (CCDC) via www.ccdc.cam.ac.uk/da-
ta_request/cif.
(15) CÀHg distances of 11 and 12 were calculated using crystal
analysis software (Mercury), which is available as a free download from
the CCDC via www.ccdc.cam.ac.uk/.
a Reactions were conducted with substrate (0.1À0.5 mmol).
b Combined yield of isolated 8 and 9. c Determined by 1H NMR
spectroscopy. d Substrate 7c was E/Z (4:1) mixture. e Substrate 7i
was E/Z (10:1) mixture.
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Org. Lett., Vol. 14, No. 9, 2012

Introduction of a dimethyl group at the β-position of the
diene does not affect the course of reaction, and the
2-allylpyrrolidine derivative 8b formed quantitatively
(entry 1). An anilinoic derivative 7c also completely re-
acted, giving 2-allylindoline 8c as a single isomer (entry 2).
Even with sec-alkyl amino derivatives 7d and 7e as sub-
strates (entries 3 and 4), good reactivity and high regios-
electivity (aswell asdiastereoselectivity16) were observed in
the formationofthe 2,5-trans-disubstitutedpyrrolidines8d
and 8e, respectively. However, an elongation of the methy-
lene unit in 7a decreased the regioselectivity to give a 91:9
mixture of 8f and 9f (entry 5). To attain complete regioselec-
tivity in the cyclization of 7f, the effect of the protecting group
on the nitrogen was investigated with several sulfonamide
derivatives. The bulkiness of the N-protecting group con-
tributed to the regioselectivity,17 and the reaction of 2,4,6-
trimethylbenzenesulfonyl (Mts)-protected 7g was found to
give 8g as the sole product in 98% yield (entry 6). This
procedure was similarly applicable to the reaction of 7h and
7i, giving the corresponding 2-allylpiperidine derivatives 8h
and 8i in excellent yields with complete regioselectivity
(entries 7 and 8). Furthermore, an attempt was made to find
the utility of the present catalytic system in CÀC bond
forming reactions. The FriedelÀCrafts-like cyclization of 7j
with 4 mol % of 12 and AgOTf was carried out at room
temperature to afford the desired allyl-substituted product 8j
in good yield with high regioselectivity (entry 9). Introduction
of a substituent into the 7j core exerted no negative influence
on the selectivity, as the diester 7k and sulfonamide derivative
7l gave the corresponding 8k and 8l in excellent yields with
complete selectivity (entries 10 and 11).
In conclusion, we have developed a carbaboranyl mer-
curic chloride and have shown that the combination of
m-carbaborane-linked 12 and AgOTf achieves intramolec-
ular cyclization of 1,3-dienes with excellent reactivity and
regioselectivity.18 Both sulfonamide and aromatic func-
tionalities can be used as nucleophiles. To the best of our
knowledge, 12 is the first example employing carbaborane
as a bulky substituent. These results will help facilitate the
synthesis of a variety of allyl cyclic compounds, which
function as potentially important synthons for the synth-
esis of natural products and pharmaceuticals.
Acknowledgment. This study was financially supported
by a Grant-in-Aid (No. 23790034) and the Senryaku
project (No. S0891078) from the MEXT (Ministry of
Education, Culture, Sports, Science, and Technology) of
the Japanese Government.
Supporting Information Available. Experimental pro-
cedures and analytical data of all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(16) 2,5-Cis-isomers were not detected. Cycloisomerizations of 7d
and 7e proceed through the conformer B which offers minimal 1,3-
diaxial interactions, consistent with the observed diastereoselectivity.
(18) The mixture of 12 and AgOTf in CH2Cl2 can be stored at room
temperature at least for several days.
(17) When using the methylsulfonamide derivative, a mixture of
allyl-type 8 and vinylene-type 9 was obtained in a 55:45 ratio.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 9, 2012
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