Oxidative Dimerization of Silylallenes via Activation of the Allenic C(sp2)-H Bond Catalyzed by Copper(I) Chloride and N-Hydroxyphthalimide

Article abstract of DOI:10.1021/acs.orglett.5b02433

Novel oxidative dimerization of silylallenes is described. Treatment of silylallenes with a catalytic amount of copper(I) chloride, a substoichiometric amount of N-hydroxyphthalamide, and a stoichiometric amount of a terminal oxidant diacetoxyiodobenzene

Full text of DOI:10.1021/acs.orglett.5b02433

Letter
pubs.acs.org/OrgLett
Oxidative Dimerization of Silylallenes via Activation of the Allenic
C(sp2)−H Bond Catalyzed by Copper(I) Chloride and
N‑Hydroxyphthalimide
Venkata R. Sabbasani and Daesung Lee*
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607, United States
S
* Supporting Information
ABSTRACT: Novel oxidative dimerization of silylallenes is described. Treatment of silylallenes with a catalytic amount of
copper(I) chloride, a substoichiometric amount of N-hydroxyphthalamide, and a stoichiometric amount of a terminal oxidant
diacetoxyiodobenzene afforded head-to-head dimers as the main products. Silyallenes containing a small ring afforded only
dimers, whereas as the ring size increased 1,3-enynes became more favorable products. For silylallenes containing an acyclic
substituent, dimer formation is a norm with exceptions where N-hydroxyphthalimide reacts at the propargylic center to generate
the corresponding aminoxy ethers.
llenes play an important role for the development of new
synthetic methods especially with transition-metal cata-
Scheme 2. Nitration of Silylallenes To Form Functionalized
Nitroalkenes
A
lysts.1 The vast array of reactions involving allenes is the
consequence of the two cumulated alkenes connected by an sp-
hydridized central carbon, which ultimately provides the
increased reactivity of their π-bonds in allenes. In particular,
allenes containing boronyl2 or silyl substituents3 are important
building blocks readily reacting with carbonyl compounds to
form homopropargylic alcohols.4,5 Because of their versatility for
further elaboration, homopropargylic alcohols are frequently
employed in various complex molecule syntheses.5j,6
which is then trapped by the nitroxyl radical (•NO) or by the
chloride nucleophile (SN1 reaction) depending on the reaction
conditions (Scheme 2, eqs 1 and 2).
Based on this facile addition of radical species with silylallenes,
we envisioned that various other radicals might also react with
these silylallenes under appropriate conditions to generate
diversely functionalized alkene products.
Recently, we developed a novel one-step protocol for the
synthesis of trisubstituted silylallenes from ketones and
(trimethylsilyl)diazomethane (Scheme 1).7 The easy access to
Scheme 1. One-Step Synthesis of Silylallenes from Ketones
To test this hypothesis, we subjected silylallene 1a to the
conditions that are known to generate an oxygen-centered
radical,9 expecting that the bis-oxygenated product should be
formed (Scheme 3). Unexpectedly, however, dimer 2a was
isolated as the sole product. Clearly, this dimerization event
implies that the putative oxygen-centered radical derived from N-
hydroxyphthalimide did not add to the central carbon of the
allene. Instead it abstracted the allenic C(sp2)−H hydrogen10 to
generated a propargylic radical, which then dimerized.11
On the basis of this initial observation, we further investigated
the oxidative the dimerization behaviors of silylallenes containing
these silylallenes prompted us to explore their unique reactivity.
Although silylallenes have been employed in many synthetic
transformations,5 their utility has not been broadly defined
especially for trisubstituted silylallenes.
The availability of these silylallens allowed us to examine their
reactivity, which resulted in novel nitration to form function-
alized nitroalkenes (Scheme 2).8 In this transformation, the
initial addition of a nitrogendioxyl radical (•NO2) occurs on the
sp-hydridized carbon to form an allylic radical intermediate,
Received: August 23, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b02433
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Scheme 3. Initial Observation of Silylallene Dimerization
Table 2. Dimerization of Silylallenes Derived from Cyclic
Ketones
different structural features, and herein we report their general
trend and selectivity.
We commenced our investigation by optimizing the reaction
conditions in terms of the catalyst loading, stoichiometry of
reagents and oxidant, reaction time, and temperature (Table 1).
Table 1. Optimization of Reaction Conditions for
Dimerization of Silylallenes
catalyst
entry (10 mol %)
N-Hpth PhI(OAc)2 temp time
a
(equiv)
(equiv)
(°C)
(h) yield (%)
1
2
3
4
5
6
7
8
CuCl
1
1
1
0
1
1
1
1
1
70
36
36
36
36
36
36
36
12
14
14
14
14
14
12
12
76
CuCl
1
78
CuCl
1
N/R
N/R
78
CuCl
0
CuCl
0.5
0.3
0.5
0.5
CuCl
40
CuOAc
Cu(OAC)2
unknown
unknown
a
Isolated yields.
Using cycloheptanylidyl allene 1a as a test substrate with a
catalytic amount of CuCl (10 mol %) and stoichiometric
amounts of N-hydroxyphthalimide (N-Hpth) and PhI(OAc)2 in
CH3CN at 70 °C gave the dimer product of 1,5-diyne 2a in 76%
yield (Table 1, entry 1). By lowering the reaction temperature
from 70 to 36 °C, the yield of the reaction was slightly increased
to 78% (Table 1, entry 2). Next, we explored the effect of the
amounts of N-Hpth and PhI(OAc)2; without oxidant and/or N-
Hpth, no reaction occurred (Table 1, entries 3 and 4). Lowering
the amount of N-Hpth down to 50 mol % did not affect the yield
of the reaction (Table 1, entry 5). However, further lowering N-
Hpth to 30 mol % significantly lower the yield of 2a (Table 1,
entry 6). Changing the catalyst from CuCl to CuOAc or
Cu(OAc)2 provided unknown products (Table 1, entries 7 and
8).
With the optimized conditions for the dimerization of silyl
allenes in hand, we next examined the substrates differing in their
ring sizes ranging from five to eight, 12, and 15 as well as the
substitution pattern around the allene skeleton (Table 2). Small
ring-based allenes 1b and 1c afforded dimers 2b and 2c in 62 and
58% yield (Table 2, entries 1 and 2), and allene 1d containing a
cyclooctylidene moiety provided a dimeric product 2d in 72%
yield (Table 2, entry 3). The reaction of allene 1e containing an
extra double bond on the eight-membered ring also yielded
dimer 2e in 68% yield without any other side product derived
from the involvement of the double bond (Table 2, entry 4).9
Unexpectedly, however, increasing the ring size beyond eight
diverted the product distribution. The reaction of allene 1f with a
a
b
Isolated yields. The ratio was determined by 1H NMR.
Protodesilylation of trimethylsilane was observed.
c
12-membered ring afforded a 2:1 mixture of dimer 2f and 1,3-
enyne 3f in 70% combined yield (Table 2, entry 5), and that of 1g
containing a 15-membered ring generated 1,3-enyne 3g in 75%
yield as a sole product (Table 2, entry 6). Carvone-derived
cyclopropane-containing silylallene 1h resulted in a 55%
combined yield of cyclopropane-opened12 3h and 1,3-enyne
B
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3h′ in a 2:1 ratio (Table 2, entry 7). On the other hand,
adamantanone-derived silylallene 1i generated an acetoxy group
trapped product 4i in 45% yield (Table 2, entry 8). The reaction
of 1a-t-Bu where the SiMe3 of 1a is replaced with a tert-butyl
group led to only decomposition under identical conditions
(Table 2, entry 9). The stark difference in reactivity between
silylallene 1a and the corresponding tert-butyl counterpart 1a-t-
Bu suggests that the silyl group plays a crucial role in weakening
the allenic C−H bond.13
Having seen the general trend of reactivity of cyaloalkane-
based silylallenes in dimerization, we next examined the reactivity
of acyclic alkane-based silylallenes toward dimerization (Table
3). Silylallene 1j bearing a prenyl group afforded dimer 2j in 72%
yield (Table 3, entry 1),14 yet a cyclopropyl group-containing
silylallene 1k resulted in severe decomposition with only a trace
amount of dimer 2k (Table 3, entry 2). Surprisingly, silylallene 1l
did not generate an expected dimer product; instead,
phthalimidoxy-trapped product 4l was generated in 34% yield.
By employing a stoichiometric amount of N-Hpth, the yield of 4l
increased to 61% (Table 3, entry 3). The results obtained from
allenes 1j, 1k ,and 1l imply that even a remote unsaturated
functional groups such as a prenyl or a phenyl group may
significantly affects the dimerization of these silylallenes. This
notion is further strengthened by the reaction of allenes 1m−p.
Although the reaction of silylallene 1m containing a terminal
double delivered only dimer product 2m in good yields (Table 3,
entry 4),14 the corresponding silylallene 1n containing a styryl
group afforded a mixture of dimer 2n14 and 1,3-enyne 3n in 69%
combined yield (Table 3, entry 5). Interestingly, allenes 1o and
1p containing different silyl groups such as SiEt3 and SiMe2-t-Bu,
respectively, delivered only the propargylic aminoxy ethers 4o
and 4p in moderate yields (Table 3, entries 6 and 7). On the
other hand, disubstituted silylallene 1q did not produce any
identifiable product but rather decomposition under identical
reaction conditions (Table 3, entry 8).
Table 3. Dimerization/Oxidation of Silylallenes Derived from
Acyclic Ketones
On the basis of this general trend and selectivity, we proposed
a tentative mechanism for the dimerization (Scheme 4). As the
Scheme 4. Proposed Reaction Mechanism
first step in the catalytic cycle, Cu(I) is oxidized to Cu(II) by
PhI(OAc)2, which then reacts with N-Hpth to generate N-Hpth-
Cu(I) adduct A. Upon homolysis of A, N-phthalimidoxy
radical9,15 B is generated together with Cu(I), which is oxidized
back to Cu(II) to reenter the catalytic cycle. In the next step, N-
phthalimidoxy radical B reacts with a substrate silylallene by
abstracting the allenic C(sp2)−H hydrogen to generate a
propargylic carbon-centered radical C and N-Hpth, which
completes the full catalytic cycle. The main downstream events
of radical C are its dimerization to form product 2 or further
oxidation to the corresponding carbocation D, which then
a
b
Isolated yields. Trace amounts of dimeric product was observed by
c
HRMS. Yields in the parentheses are from reactions with 1 equiv of
N-hydroxypthalimide. Protodesilylation was observed.
d
C
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́
undergoes an elimination and/or substitution to generate
products 3 and/or 4, respectively.
In summary, we have discovered a novel oxidative
dimerization reaction of silylallenes using a catalytic system of
copper(I) chloride and N-hydroxyphthalamide (N-Hpth) along
with a stoichiometric amount of a terminal oxidant diacetox-
yiodobenzene. Noticeable dependency on substrate structure for
the formation of dimers, 1,3-enynes, and N-Hpth adducts was
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plausible mechanism for the reaction, which involved the
abstraction of the allenic C(sp2)−H hydrogen by N-phthalimi-
doxy radical to generate a propargylic carbon-centered radical as
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ASSOCIATED CONTENT
* Supporting Information
Experimental procedures, characterization data, spectral repro-
ductions for all new compounds, and cif for 2d and 2f. The
Supporting Information is available free of charge on the ACS
Publications website at DOI: 10.1021/acs.orglett.5b02433.
■
S
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(10) (a) Laporterie, A.; Dubac, J.; Manuel, G.; Del
́ ́
eris, G.; Kowalski, J.;
Experimental procedures, characterization data, and
spectral reproductions for all new compounds (PDF)
X-ray crystallographic data for 2d (CIF)
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X-ray crystallographic data for 2f (CIF)
AUTHOR INFORMATION
Corresponding Author
■
(11) Radical dimerization reactions: (a) Yang, F.; Zhao, G.; Ding, Y.;
Zhao, Z.; Zheng, Y. Tetrahedron Lett. 2002, 43, 1289. (b) Lathrop, S. P.;
Kim, J.; Movassaghi, M. Chimia 2012, 66, 389. Review: (c) Melikyan, G.
G. Acc. Chem. Res. 2015, 48, 1065.
*E-mail: dsunglee@uic.edu.
Notes
(12) Cyclopropane ring opening recent review: Cavitt, M. A.; Phun, L.
H.; France, S. Chem. Soc. Rev. 2014, 43, 804.
The authors declare no competing financial interest.
(13) Accepted for publication: Sabbasani, V. R.; Huang, G.; Xia, Y.;
Lee, D. Chem.−Eur. J. 2015.
ACKNOWLEDGMENTS
■
(14) On the basis of the 1H and 13C NMR, 2j, 2m, and 2n are single
diastereomers.
We thank UIC (LAS-AFS), NSF (CHE-0955972), and
TACOMA Technology for financial support. We thank Prof.
Neal Mankad (UIC) for his help in obtaining X-ray structures.
The mass spectroscopy department at UIUC is greatly
acknowledged.
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Y.; Iwahama, T.; Sakaguchi, S.; Nakayama, K.; Nishiyama, Y. J. Org.
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S.; Mo, D.-L.; Wang, H.-Y.; Mueller, D. S.; Anderson, L. L. Angew. Chem.,
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