Subtle electronic effects in metal-free rearrangement of allenic alcohols

Article abstract of DOI:10.1021/ol400331r

A general and stereoselective rearrangement of allenic alcohols to (E,E)-1,3-dien-2-yl triflates and chlorides was developed under metal-free conditions. Subtle electronic effects of the alkyl and aryl substituents on the carbon bearing the hydroxyl group has a profound impact on the reaction rate and efficiency such that vinyl triflates were obtained from electron-deficient substrates and trimethylsilyl triflate whereas vinyl chlorides were generated with an electron-rich substrate and trimethylsilyl chloride.

Full text of DOI:10.1021/ol400331r

ORGANIC
LETTERS
2013
Vol. 15, No. 7
1552–1555
Subtle Electronic Effects in Metal-Free
Rearrangement of Allenic Alcohols
Venkata R. Sabbasani,† Phani Mamidipalli,† Huijie Lu,‡ Yuanzhi Xia,‡ and
Daesung Lee*,†
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607, United States, and College of Chemistry and Materials
Engineering, Wenzhou University, Wenzhou, Zhejiang Province 325035, P. R. China
dsunglee@uic.edu
Received February 4, 2013
ABSTRACT
A general and stereoselective rearrangement of allenic alcohols to (E,E)-1,3-dien-2-yl triflates and chlorides was developed under metal-free
conditions. Subtle electronic effects of the alkyl and aryl substituents on the carbon bearing the hydroxyl group has a profound impact on the
reaction rate and efficiency such that vinyl triflates were obtained from electron-deficient substrates and trimethylsilyl triflate whereas vinyl
chlorides were generated with an electron-rich substrate and trimethylsilyl chloride.
Allylic 1,3-transposition of CÀO bonds across a
π-system is an important transformation in organic syn-
thesis. The 1,3-transposition of allylic1 and propargylic2
Scheme 1
† University of Illinois at Chicago.
‡ Wenzhou University.
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Hayashi, Y. Tetrahedron 1992, 48, 2059–2068. (c) Gordon, M. S.;
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alcohols and their acyl derivatives has been exten-
sively studied under oxo-metal or Lewis acid catalyzed
conditions (Scheme 1, eqs 1 and 2). On the other hand,
the corresponding rearrangement of allenic alcohols
or their derivatives (eq 3) has been virtually ignored
until recently except for a few examples. Trost realized
aldol reactions between aldehydes and enolates de-
rived from allenic alcohols via 1,3-transposition in the
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r
10.1021/ol400331r
Published on Web 03/21/2013
2013 American Chemical Society

presence of an oxo-vanadium catalyst.3 Alcaide ob-
served the formation of mesylated 1,3-dienes upon
treating allenic alcohols with methanesulfonyl chlor-
ide and triethylamine.4a,b Recently, the conversion of
terminal allenic alcohols to 2-halo-1,3-dienes was ob-
served in the presence of a stoichiometric amount of
iron(III) halide.4
Table 1. Synthesis of Allenyl Alcohols from Terminal
Propargylic Alcohols and Ethyl Diazoacetate Catalyzed by CuI
In our continued interest in allylic 1,3-transposition
chemistry5 coupled with functionalized 1,3-diene syn-
theses, we envisioned that the rearrangement of allenic
alcohols shown in eq 3 should offer a unique opportunity
not only for the exploration of their rearrangement under
metal-catalyzed or metal-free conditions6 but also for
developing a new approach for stereoselective synthesis
of functionalized 1,3-dienes. Previously reported typical
syntheses of functionalized dienes involve metal-catalyzed
coupling reactions,7 elaborations of allenol derivatives8
and vinyl ketones9 but proceeded with poor selectivity,
or were applied only to the synthesis of dienes with one
terminal double bond.
In this regard, we envisioned that the significant thermo-
dynamic driving force for the conversion of allenic
alcohols to a substituted 1,3-dienes in eq 3 can be exploited
to develop an efficient and stereoselective method for
functionalized 1,3-dien-2-yl triflates and chlorides, which
are versatile intermediates in organic synthesis. For exam-
ple, these functionalized 1,3-dienes are viable building
blocks to be engaged in a complex molecule synthesis10
via DielsÀAlder reactions and related cycloadditions.
Recently, these dienyl triflates and halides were used as
substrates for the preparation of chiral allenes.11 Herein we
report a general and stereoselective rearrangement of
allenic alcohols to (E,E)-1,3-dien-2-yl triflates and chlor-
ides under metal-free conditions where the subtle electro-
nic effect of the alkyl and aryl substituents on the
substrates has a profound impact on the reaction rate
and efficiency.
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a Isolated yield after runningthe reaction at room temperature for 3 h
followed by purification by flash chromatography.
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First, by modifying the conditions for copper-catalyzed
coupling of terminal alkynes 1aÀr and ethyl diazoacetate
reported by Fu,12 we optimized the synthesis of allenic
alcohols 2aÀr (Table 1).13 It was found that the addition of
Org. Lett., Vol. 15, No. 7, 2013
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Table 2. Reagent Screening for 1,3-Transposition
Table 3. Scope of the Allylic 1,3-Transposition with TMSOTf
and TMSCl
temp
time
(h)
yield
(%)a E/Zb
entry
reagent
equiv
(°C)
1
2
3
4
5
6
7
8
9
TMSOTf
TMSOTf
TMSOTf
TMSCI
TMSI
1
2
2
1
3
1
1
1
1
rt
rt
1
3a
3a
3a
4a
4a
4a
5a
5a
5a
53c
63
1:0
1:0
1:0
35:1
33:0
1:0
À
0.5
0.5
2
À78 to rt
77
rt
65d
89
rt
1
POCl3
rt
2
35
e
TMSBr
TMSBr
PBr3
rt
0.5
0.5
1
À
À78
rt
92
78
14:1
1:1
a Isolated yield. b E/Z ratio was determined by 1H NMR, and the
stereochemistry of the products was determined by 1H NOE. c Only 70%
conversion, and the yield is based on recovered starting material. d Only
45% conversion, and the yield is based on recovered starting material.
e Decomposition of 2a.
a stoichiometric amount of triethylamine to the reaction
effectively isomerized the alkynyl alcohols to the corre-
sponding allenic alcoholsin excellent yield regardless of the
nature of the substituents. Because of the secondary
alcohol and disubstituted allene stereogenic units, these
allenic alcohols were obtained as a mixture of diastereo-
mers (1:1). In addition, it was found that the hydroxyl
group at the propargylic center plays an important role in
facilitating the isomerization of the alkyne to the allene.
Under the same conditions, terminal alkynes without the
hydroxyl group provided a mixture of the alkyne- and
allene-containing coupled products.14
Next, we examined the allylic transposition of allenic
alcohol 2a under various metal-free conditions employing
TMSOTf, TMSCl, POCl3, TMSBr, and PBr3 (Table 2).
Treatment of allenic alcohol 2a with TMSOTf (1 equiv) at
room temperature for 1 h provided vinyl triflate 3a as a
single isomer in 53% yield (entry 1). The yield of 3a was in-
creased to 63% with 2 equiv of TMSOTf for 0.5 h (entry 2),
and further up to 77% by running the reaction at lower
temperature (entry 3). Reactions with TMSCl provided vinyl
chloride 4a with good selectivity in 65% yield (E/Z = 35:1)
ꢀ
(12) Suarez, A.; Fu, G. C. Angew. Chem., Int. Ed. 2004, 43, 3580–
3582.
1
a Isolated yields. b E/Z ratio was determined by H NMR, and the
stereochemistry was determined by NOE. c Decomposition with
TMSOTf. d No reaction with TMSCl. e After heating up to 150 °C, 2d
was recovered (70%). f Unknown product was formed. g Decomposition
with TMSCl. h Very low conversion even with 5 equiv of TMSCl. i Excess
TMSCl (5 equiv) was used for full conversion. j During the purification,
vinyl triflate 3s hydrolyzed to trans-4-phenyl-3-buten-2-one.
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R. P. Acc. Chem. Res. 2003, 36, 773–782. (b) Ma, S. Chem. Rev. 2005,
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Nakajima, K.; Takahashi, T. Org. Lett. 2009, 11, 177–180. (i) Zhang,
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Org. Lett. 2011, 13, 2388–2391.
€
ꢀ
after 2 h (based on 45% conversion) when 1 equiv of
the reagent was employed (entry 4). The yield of 4a
increased to 89% (E/Z = 33:1) with 3 equiv of TMSCl
(entry 5). A single isomer of vinyl chloride 4a could be
obtained from the reaction with POCl3 but only in 35%
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Org. Lett., Vol. 15, No. 7, 2013

yield (entry 6). While a more reactive reagent such as
TMSBr rendered the decomposition of the substrate at
room temperature, the expected bromide 5a was obtained
in good yield and selectivity at À78 °C (entries 7 and 8).
Also the reaction with PBr3 afforded 5a in 78% yield as a
mixture of E/Z-isomers in a 1:1 ratio (entry 9). In all cases,
the 1,3-diene products are trans in the styryl unit.
transition state E-TS, where the approach of a chloride
ion is from the side of the hydrogen as opposed to that of
the methoxycarbonyl group in Z-TS, generating E-4a-Me
predominantly. The energy difference between these two
TSs (À10.2 kcal/mol) is consistent with the observed high
E/Z-selectivity in the product. On the basis of this model
calculation, we surmise that the 1,3-transpositions of other
substrates induced by TMSOTf and TMSBr also proceed
through a similar mechanism. The six-membered ring
TSs also can explain the lack of products without the
1,3-position in these reactions.
In order to extend the scope of this rearrangement, a
variety of allenic alcohols were treated with TMSOTf and
TMSCl and the results are shown in Table 3. When treated
with both TMSOTf and TMSCl, substrates 2b and 2i with
the 4-chlorophenyl and cinnamyl group afforded dienyl
triflate 3b/3i and dienyl chloride 4b/4i, respectively, with
good yields and E/Z-selectivity (entries 1 and 8). However,
allenic alcohols 2dÀf possessing electron-withdrawing
groups on the aromatic ring (entries 4À6) or 2j/2k contain-
ing alkynyl substituents (entries 9 and 10), showed good
reactivity profiles with TMSOTf, yielding the correspond-
ing dienyl triflates 3dÀf and 3j/3k in good yields, but were
found to be inert (2d, 2f, 2j, 2k) or afforded an unidentified
material (from 2e) with TMSCl. Interestingly, only the
alkyne-substituted substrates 3j and 3k showed relatively
low E/Z-selectivity (5:1 and 3.5:1). On the other hand,
upon increasing the electron-donating nature of the
aryl/heteroaryl groups such as in allenic alcohols 2c, 2g,
and 2h (entries 2, 6, and 7), the opposite reactivity profiles
were observed, where the decomposition of substrates was
observed with TMSOTf, yet excellent yields and selectivity
of dienyl chlorides 4c, 4g, and 4h were obtained with
TMSCl with the exception of the low selectivity of 4h
(E/Z = 1.5:1). Secondary allenic alcohols 2lÀn with either
cyclic or acyclic alkyl substituents (entries 11À13) reacted
with TMSOTf to deliver dienyl triflates 3lÀn in good yields
and selectivity, but they are virtually inert with TMSCl. On
the other hand, tertiary allenic alcohols 2oÀq (entries
14À16) decomposed with TMSOTf yet provided E-dienyl
chlorides 4lÀn in acceptable yields. A terminal allenic
alcohol 2s without an ester group afforded the correspond-
ing dienyl triflate 3s and chloride 4s upon treatment with
TMSOTf and TMSCl, respectively (entry 17). These re-
sults clearly demonstrate the need for a delicate balance
of the electronic effect of the substituents in the substrates
and reactivity of TMSOTf and TMSCl for the observed
1,3-transposition.15
Scheme 2. DFT-Calculated TSs of 1,3-Transposition of 2a-Me
˚
with TMSCl (M06-2X/6-31G*/PCM Level; Distances are in A)
In summary, an efficient metal-free rearrangement of
allenic alcohols bearing aromatic, conjugated, or aliphatic
substituents to the corresponding 1,3-dienyl triflates and
chlorides has been developed by using TMSOTf and
TMSCl. Clearly, the driving force of this 1,3-transposition
is the formation of more stable conjugated dienes. The
effective synthesis of tri- and tetrasubstituted 1,3-dienes
with excellent E/Z-selectivity by instituting the sequential
formation of allenic alcohols from readily available build-
ing blocks followed by their rearrangement under metal-
free conditions makes this process synthetically valuable.
Acknowledgment. Financial support for this work from
the National Science Foundation (CHE 0955972) for D.L.
and NSFC (21002073) for Y.X. is greatly acknowledged.
We are grateful to Mr. Furong Sun of the University of
Illinois at UrbanaÀChampaign for high resolution mass
spectrometry data.
To gain insight into the mechanism, we carried out brief
DFT caculations (M06-2X/6-31G*/PCM Level) for the
transition state (TS) of the 1,3-rearragement of 2a-Me
(methyl ester equivalent of 2a) with TMSCl (Scheme 2).
The calculated TSs show that the rearrangement occurring
with hydrogen bonded intramolecular delivery of a chlo-
ride ion is the most favorable reaction pathway. The E/Z-
selectivity can be rationalized by the more favorable
Supporting Information Available. Experimental pro-
cedures and spectroscopic data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(15) A related example with the corresponding vinylogous system:
Jiang, H.; Gao, Y.; Wanqing, W.; Huang, Y. Org. Lett. 2013, 15, 238–
241.
The authors declare no competing financial interest.
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