Complementary iron(II)-catalyzed oxidative transformations of allenes with different oxidants

Article abstract of DOI:10.1002/anie.201510006

Substituent- and oxidant-dependent transformations of allenes are described. Given the profound influence of the substituent on the reactivity of allenes, the subtle differences in allene structures are manifested in the formation of diverse products when reacted with different electrophiles/oxidants. In general, reactions of nonsilylated allenes involve an allylic cation intermediate by forming a C-O bond, at the sp-hybridized C2, with either DDQ (2,3-dichloro-5,6-dicyano-p-benzoquinone) or TBHP (tert-butyl hydroperoxide), along with FeCl₂·4 H₂O (10 mol %). In contrast, silylated allenes favor the formation of propargylic cation intermediates by transferring the allenic hydride to the oxidant, thus generating 1,3-enynes (E1 product) or propargylic THBP ethers (S_N1 product). The formation of these different putative cationic intermediates from nonsilylated and silylated allenes is strongly supported by DFT calculations. Profound impact: Iron(II)-catalyzed transformations of allenes induced by either DDQ or tBuOOH depend on the substituent on the allenes. Nonsilylated and silylated allenes show complementary reactivity upon exposure to DDQ and tBuOOH in the presence of an iron(II) catalyst. Nonsilylated allenes incorporate the oxidant at the sp-hybridized carbon, whereas the silylated allenes generate 1,4-dehydrogenated 1,3-enynes. DDQ=2,3-dichloro-5,6-dicyano-1,4-benzoquinone.

Full text of DOI:10.1002/anie.201510006

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International Edition: DOI: 10.1002/anie.201510006
German Edition: DOI: 10.1002/ange.201510006
Oxidation
Complementary Iron(II)-Catalyzed Oxidative Transformations of
Allenes with Different Oxidants
Venkata R. Sabbasani, Hyunjin Lee, Yuanzhi Xia,* and Daesung Lee*
Abstract: Substituent- and oxidant-dependent transformations
of allenes are described. Given the profound influence of the
substituent on the reactivity of allenes, the subtle differences in
allene structures are manifested in the formation of diverse
products when reacted with different electrophiles/oxidants. In
general, reactions of nonsilylated allenes involve an allylic
À
cation intermediate by forming a C O bond, at the sp-
hybridized C2, with either DDQ (2,3-dichloro-5,6-dicyano-p-
benzoquinone) or TBHP (tert-butyl hydroperoxide), along
with FeCl2·4H2O (10 mol %). In contrast, silylated allenes
Scheme 1. Polar reaction versus single-electron-transfer processes of
electron-rich allenes.
favor the formation of propargylic cation intermediates by
transferring the allenic hydride to the oxidant, thus generating
1,3-enynes (E1 product) or propargylic THBP ethers (SN1
product). The formation of these different putative cationic
intermediates from nonsilylated and silylated allenes is strongly
supported by DFT calculations.
conditions to generate structurally diverse oxidation products.
In general, nonsilylated allenes provided products by tradi-
tional reaction pathways involving the cation intermediate
IN1, whereas the corresponding silylated counterparts lead to
either E1 or SN1 products by unprecedented oxidation
pathways involving the propargylic cation intermediate IN2.
The mechanistic aspects of these two different modes of
reactions were further verified by DFT calculations.
O
ur recent investigations on new reactivity of allenes
revealed that the silyl substituent has profound influence on
their reaction course.[1,2] For example, in the Alder ene
2
À
reaction, the allenic C(sp ) H bond is more active than allylic
C(sp ) H bonds. Density-functional theory (DFT) calcula-
tions revealed that the main source of this unexpected
reactivity is the weakening of the allenic C(sp ) H bond
(Scheme 1). Compared to the nonsilylated allene 1, the
corresponding silylated counterpart 2 has an unusually weak
C(sp ) H bond (82.2 kcalmol ), which is even lower than
3
[2]
À
Differentiation of the reactivity between 1a and 2a was
investigated with two different oxidants, DDQ and TBHP,
under iron-catalyzed reaction conditions (Scheme 2).[5–7]
2
À
2
À1
À
3
À1
À
that of a typical allylic C(sp ) H bond by 5 kcalmol . In
addition, the natural population analysis (NPA) indicates that
the sp-hybridized C2 in 2 imparts significantly less positive
charge character relative to that of 1 and may cause the
formation of complementary cationic intermediates such as
IN1 and IN2 by different reagents.[3,4] Therefore, depending
on the choice of electrophiles or oxidants, the subtle differ-
ence in reactivity of structurally different allenes can be
manifested to generate different final products.
Described herein are clear demonstrations of novel
complementary reactivity of allenes under different reaction
[*] V. R. Sabbasani, H. Lee, Prof. D. Lee
Department of Chemistry, University of Illinois at Chicago
845 West Taylor Street, Chicago, IL 60607 (USA)
E-mail: dsunglee@uic.edu
Scheme 2. Initial proof of complementary reactivity of nonsilylated and
silylated allenes with DDQ. DDQ=2,3-dichloro-5,6-dicyano-1,4-benzo-
quinone, TBS=tert-butyldimethylsilyl.
Prof. Y. Xia
College of Chemistry and Materials Engineering, Wenzhou University
Wenzhou, Zhejiang Province 325035 (P.R. China)
E-mail: xyz@wzu.edu.cn
Through brief optimization (see the Supporting Information),
it was found that treating 1a with DDQ and FeCl2·4H2O as
the catalyst (Conditions A) generated the indene derivative
3a (91%).[8,9] In contrast, by replacing DDQ with TBHP and
using a slightly higher temperature (Conditions B), a single
Supporting information and ORCID(s) from the author(s) for this
article are available on the WWW under http://dx.doi.org/10.1002/
anie.201510006.
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diastereomer of the a-peroxy indanone 4a was obtained
(91%). Under similar reaction conditions, the silylated allene
2a afforded 1,3-enyne 5a as a single isomer (98%) with DDQ
(Conditions C),[10] whereas with TBHP (Conditions D), the
corresponding propargylic peroxy ether 6a was obtained
(93%).
On the basis of these diverse reactivities, we further
explored a series of phenyl-group-containing trisubstituted
allenes[11] under Conditions A (Table 1). Both gem-phenyl,-
did not afford the corresponding products 3 f and 3g; instead
the starting material was recovered (entry 5). The cycloalkyl-
based allene 1h afforded the DDQ-incorporated 1,3-diene 3h
(entry 6). The gem-diphenyl-substituted allenes 1i and 1j,
bearing tert-butyl and ethyl groups, respectively, behaved
similarly, thus generating the corresponding 3i (85%) and 3j
(93%; entries 7 and 8). The unsymmetrical gem-diphenyl-
substituted allenes 1k and 1l, carrying p-fluoro and p-
methoxy substituent, respectively, provided the correspond-
ing mixtures of 3k/3k’ (10:1) and 3l/3l’ (1:3.5), thus showing
the preferential participation of the more electron-rich aryl
group (entries 9 and 10). This preference was further dem-
onstrated by the allene 1m, having phenyl and 3,4,5-
trimethoxyphenyl groups, and it exclusively afforded the
indene derivative 3m (entry 11).
Table 1: Iron-catalyzed reaction of alkyl,aryl-substituted allenes with
DDQ.
We further examined the reactivity of these phenyl-
substituted allenes[11] under reaction Conditions B (Table 2).
Table 2: Reactions of alkyl,aryl-substituted allenes with TBHP.
[a] Yield of isolated product. [b] The ratio was determined by 1H NMR
analysis. [c] Recovered starting material. [d] During purification 3h was
further oxidized to the corresponding naphthalene derivative 3h’ (ca.
10%).
[a] Yield of product after purification. [b] Single diastereomer was
observed.
The gem-phenyl,methyl- and gem-diphenyl-substituted
allenes 1b, 1j, and 1m afforded the corresponding propar-
gylic peroxy ethers 4b, 4i, and 4m in excellent yields
(entries 1–3). For the allene 1k, containing phenyl and 4-
fluorophenyl groups, the the isomeric products 4k and 4k’
were generated in a 1:1 ratio (entry 4). The allenes 1n–p,
bearing a cinnamyl group, provided the cyclopentenone
derivatives 4n–p without incorporation of peroxy ether in
marginal yields (entries 5–7). In all cases a single diastereo-
mer was obtained. The relative stereochemistry of the
methyl- (1b) and gem-phenyl,benzyl-substituted (1c) allenes
provided 3b’ and 3c’, respectively, as a minor component
together with the major products 3b and 3c (entries 1 and 2),
whereas 1d, containing a w-silyloxypropyl group, provided 3d
exclusively (entry 3). When a competing nucleophile such as
a hydroxy group exists on the allene, it participated prefer-
entially over the phenyl group, thus generating a mixture of
3e and 3e’ in a 1:6.5 ratio (entry 4). The disubstituted allenes
1 f and 1g having a tert-butyl and phenyl group, respectively,
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Table 4: Iron-catalyzed oxidative transformation of silyl allene and
TBHP.
product 4i was confirmed unambiguously by X-ray diffraction
analysis.[12]
Next, we investigated the reaction profiles of structurally
diversified silylated allenes[13] under reaction Conditions C
(Table 3). Unsymmetrically substituted silylated allenes (2b–
Table 3: Iron-catalyzed oxidative transformation of silyl allenes with
DDQ.
[a] Yield of isolated product.
propargylic tert-butyl propargylic peroxides 6 f, 6n, 6i, 6o, 6j,
6k, and 6p[12] in excellent yields (entries 7–13).
[a] Yield of isolated product. [b] The ratio was determined by 1H NMR
analysis. [c] The low yield was due to its volatility.
To gain insight into the reactivity and selectivity of these
allene-based transformations, DFT calculations were carried
out (Scheme 3). For nonsilylated allenes, clearly the tBu-TS1
e) afforded the regioisomeric 1,3-enynes 5b–e, where differ-
ent silyl groups (TES, TBS, TIPS) have little influence on the
yields (entries 1–3). The cyclopropyl-substituted allene 2e
afforded the 1,3-enyne 5e in low yield, which is mainly due to
its volatility (entry 4). The symmetrical cyclic gem-dialkyl-
substituted allenes 2 f–k provided the corresponding 1,3-
enynes 5 f–k as the only products in good yield (entries 5–11).
The reactivity of these silylated allenes[13] was further
explored under the reaction Conditions D (Table 4). Differ-
ent silylated allenes, 2b (SiEt3), 2c (SiMe2tBu), and 2d
(SiiPr3), reacted smoothly to provide the corresponding the
propargylic peroxides 6b, 6c, and 6d in good yields (entries 1,
2 and 3). While the cyclopropyl allene 2e delivered the tert-
butyl propargylic peroxide 6e in 70% yield (entry 4), the
silylallene 2l led to the propargylic peroxide 6l in excellent
yields (entry 5). The silylated allene 2m, with a prenyl group,
formed only the corresponding propargylic peroxide product
6m in moderate yield, without a change to the double bond in
the prenyl group (entry 6). The silylated allenes 2 f, 2n, 2i, 2o,
2j, 2k, and 2p reacted smoothly to the provide corresponding
Scheme 3. Mechanisms for the transformations of alkyl- and silyl-
substituted allenes with DDQ (relative free energies (in kcalmolÀ1
)
were calculated at the M06-2X/6-31+G* level of theory; details are
given in the Supporting Information).
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(19.8 kcalmolÀ1), with DDQ interacting at C2 to generate an
allylic cation,[11] tBu-IN1 (5.9 kcalmolÀ1), is significantly more
favorable than its reaction via tBu-TS1’ (22.9 kcalmolÀ1) by
a hydride transfer to generate tBu-IN1’ (9.3 kcalmolÀ1). In
contrast, silylated allenes show the opposite preference. The
transition-state SiMe3-TS1’ (18.8 kcalmolÀ1), resulting from
a hydride transfer to generate SiMe3-IN1’ (5.1 kcalmolÀ1), is
lower in energy by 1.6 kcalmolÀ1 than that of SiMe3-TS1
(20.4 kcalmolÀ1), where DDQ interacts at C2 to generate
SiMe3-IN1 (6.2 kcalmolÀ1).[14] These energy profiles of the
initial bond-forming step leading to different products clearly
support the observed mode-selective reactions of nonsilylated
allenes.[15,16]
technology (D.L.), the Zhejiang Provincial NSF
(LY13B020007, Y.X.), and NSFC (21372178 and 21572163,
Y.X.) for financial support.
Keywords: allenes · density-functional calculations · iron ·
oxidation · synthetic methods
How to cite: Angew. Chem. Int. Ed. 2016, 55, 1151–1155
Angew. Chem. 2016, 128, 1163–1167
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Received: October 27, 2015
Revised: November 10, 2015
Published online: December 7, 2015
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