Copper(I)-catalyzed stereoselective synthesis of (1E,3E)-2- sulfonyl-1,3-dienes from N-propargylic sulfonohydrazones

Article abstract of DOI:10.1002/adsc.201300126

A new method for the stereoselective synthesis of highly substituted (1E,3E)-2-sulfonyl-1,3-dienes from N-propargylic sulfonohydrazone derivatives has been developed via copper(I)-catalyzed [3,3] rearrangement and highly regioselective migration of the sulfonyl group. Copyright

Full text of DOI:10.1002/adsc.201300126

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DOI: 10.1002/adsc.201300126
Copper(I)-Catalyzed Stereoselective Synthesis of (1E,3E)-2-
Sulfonyl-1,3-dienes from N-Propargylic Sulfonohydrazones
Yu Zhu,a Hai-Tao Tang,a and Zhuang-Ping Zhana,*
a
Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, Fujian,
Peopleꢀs Republic of China
Fax : (+86)-592-218-0318; e-mail: zpzhan@xmu.edu.cn
Received: February 7, 2013; Revised: March 18, 2013; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300126.
Abstract: A new method for the stereoselective
synthesis of highly substituted (1E,3E)-2-sulfonyl-
1,3-dienes from N-propargylic sulfonohydrazone de-
rivatives has been developed via copper(I)-cata-
lyzed [3,3]rearrangement and highly regioselective
migration of the sulfonyl group.
zones 1 undergo a novel [3,3]rearrangement and ste-
reoselective shift of the sulfonyl group[4a,7] catalyzed
by copper(I) and eventually furnish (1E,3E)-2-sulfo-
nyl-1,3-dienes
(Scheme 1).
2
in moderate to good yields
The 2-sulfonyl-1,3-dienes have been deemed to be
versatile synthons in organic transformations. The 2-
sulfonyl-1,3-diene moiety offers a handle for transfor-
mation into various other skeletons via Diels–Alder
reactions[8] or Michael additions.[9] Moreover, epoxi-
dation of either double bond of 2-sulfonyl-1,3-dienes
leads to synthetically useful epoxy sulfones.[10] Howev-
er, the stereocontrolled synthesis of 1,3-diene sulfones
has rarely aroused extensive attention. The previous
Keywords: migration of the sulfonyl group; N-prop-
argylic sulfonohydrazone;
ACHTUNGTRENNUNG(1E,3E)-2-sulfonyl-1,3-dienes
ACHTUNGERTN[NUNG 3,3] rearrangements;
Metal-catalyzed skeletal rearrangements which in- procedures for the synthesis of 2-sulfonyl-1,3-dienes
volve cleavage and formation of several covalent involved reagents such as Hg,[11] Se,[12] thiophenol[13]
bonds have been known as an effective pathway for organic tin[14] or strong base.[15] These processes have
the construction of complex molecules. In particular, drawbacks with regard to convenient synthesis and
the [3,3]rearrangements of propargylic systems have disadvantageous effects on the environment.
been well studied (Scheme 1).[1] Propargyl carboxy-
On the basis of work that has been previously car-
lates as substrates have demonstrated a diversity of ried out in our laboratory,[16] N-propargylic sulfonohy-
the skeletal rearrangement which offers versatile en- drazones 1 could be easily prepared through FeCl3-
tries into a range of fascinating structures.[2] The catalyzed nucleophilic substitution of propargylic ace-
Claisen rearrangement of propargyl vinyl ethers con- tates with hydrazones in a single synthetic step, all of
stitutes a synthetically convenient route to b-allenic which are easily accessible. In the initial study, we de-
alcohols, substituted furans, 2H-pyrans or multifunc- cided to investigate the reaction conditions in order
tionalized aromatic products.[3] Similar approaches to to improve the yield using 1a as the reactant
preparing pyrrole derivatives from aza-Claisen rear- (Table 1). The reaction was smoothly catalyzed by
rangement of N-propargylic enaminone derivatives CuI and CuCl in toluene and the desired product 2a
have been accomplished.[4] Overman and his co-work- was isolated in 78% and 60% yields, respectively
ers reported the rearrangement of propargylic tri- (Table 1, entries 1 and 2). Gratifyingly, the reaction
chloroacetimidates to form allenamides, 1,3-dienes rate increased dramatically catalyzed by 5 mol%
and 2-pyridones (Overman rearrangement).[5] Recent- [CuPPh3I]4 and a higher yield was achieved (Table 1,
ly, the palladium-catalyzed [3,3]rearrangement of entry 4). When CuACHTNUTRGNE(UNG PPh3)3I was utilized under the
propargylic phosphorimidates for the facile synthesis same conditions, the reaction proceeded slowly to
of allenyl phosphoramidates has been described by afford 2a in 60% yield (Table 1, entry 5). The Lewis
Mappꢀs group.[6]
acid CuACTHNGUTRENNU(G OTf)2 failed to promote this transformation
To the best of our knowledge, a [3,3]rearrangement (Table 1, entry 3). The reaction took place in a less ef-
of N-propargylic hydrazones has not been disclosed. fective manner when using solvents such as CH3CN
Herein, we report that N-propargylic sulfonylhydra- (20%),THF (0) and DMF (0) (Table 1, entries 6, 7
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and 8). Absence of the catalyst led to complete recov-
ery of 1a (Table 1, entry 9).
To broaden the scope of this reaction, we carried
out the reaction of the N-propargylic sulfonohydra-
zone derivatives (summarized in Table 2) under the
optimized conditions. The substrates 1a (R1 =4-
MeC6H4) and 1c (R1 =C6H5) gave the desired results,
providing 2-sulfonylbuta-1,3-dienes 2a and 2c in 85%
and 87% yields, respectively (Table 2, entries 1 and
3). The electron-deficient sulfonohydrazone 1b (R1 =
4-BrC6H4) reacted smoothly affording the product 2b
in 91% yield (Table 2, entry 2). The electron-donating
sulfonohydrazone 1d (R1 =4-MeOC6H4) was also suc-
cessfully employed in the reaction to give product 2d
in 65% yield (Table 2, entry 4). Obviously, electron-
poor sulfonohydrazones provided the desired prod-
ucts in higher yields than electron-rich sulfonohydra-
zones. The substrates 1e, 1n and 1o bearing a fused
ring or thiophene moiety were also suitable for the
transformations (entries 5, 14 and 15). Electron-neu-
tral, electron-deficient, and electron-rich aromatic
groups (R2 and R3) on 1 were all well tolerated, and
the desired products (2f–2l) were obtained in moder-
ate to good yields (75–92%, Table 2, entries 6–12).
The reaction of 1m (R3 =2-OHC6H4) containing
a weakly acidic hydroxy group also afforded 2m in
moderate yield (Table 2, entry 13). Additionally, inter-
nal alkynes 1p and 1q (R4 =n-C4H9 and cyclopropan-
yl) readily underwent this tandem reaction to afford
substituted alkenes 2p and 2q in moderate yields
(Table 2, entries 16 and 17). Methylsulfonylhydrazone
1r (R1 =Me) also afforded the corresponding migra-
tion product in low yield (Table 2, entry 18). Howev-
er, the results suggested that reactants 1s (R4 =H)
and 1t (R2 =H) failed to form 2-sulfonyl-1, 3-dienes
(Table 2, entries 19 and 20). The reaction of acetohy-
drazone 1u and methoxycarbonylhydrazone 1v did
Scheme 1. Rearrangements of the propargylic system.
Table 1. Optimization of the reaction conditions.[a]
Entry Catalyst
Solvent Time [h] Yield[b]
1
2
3
4
5
6
7
8
9
20 mol% CuI
20 mol% CuCl
20 mol% Cu(OTf)2
5 mol% [Cu
20 mol% Cu
PhMe
PhMe
PhMe
12
12
12
6
78%
60%
complex
85%
60%
20%
n.r.[c]
n.r.[d]
n.r.
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
A
8
5 mol% [Cu
5 mol% [Cu
5 mol% [Cu
–
ACHTUGNTRNE(UNNG PPh3)I]4 CH3CN 15
A
AHCTUNGTRENNUNG
12
12
12
[a]
Conditions: 1a (234 mg, 0.5 mmol), solvent (2 mL),
reflux.
Isolated yields.
n.r.=no reaction.
The reaction was performed below 1208C.
[b]
[c]
[d]
Figure 1. X-ray structure of 2i.
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Copper(I)-Catalyzed Stereoselective Synthesis of (1E,3E)-2-Sulfonyl-1,3-dienes
Table 2. Copper(I)-catalyzed formation of 2-sulfonyl-1,3-dienes.[a]
Entry
1
Substrates 1: R1; R2; R3; R4
Products 2
Yield[b]
1a: 4-MeC6H4; C6H5; C6H5; C6H5
85% (2a)
2
3
4
5
1b: 4-BrC6H4; C6H5; C6H5; C6H5
1c: C6H5; C6H5; C6H5; C6H5
91% (2b)
87% (2c)
65% (2d)
60% (2e)
1d: 4-MeOC6H4; C6H5; C6H5; C6H5
1e: 4-MeC6H4; 1-naphthyl; C6H5; C6H5
6
7
8
1f: 4-MeC6H4; 4-BrC6H4; 4-MeC6H4; C6H5
1g: C6H5; 4-FC6H4; C6H5; C6H5
82% (2f)
87% (2g)
92% (2h)
1h: 4-MeC6H4; 4-MeOC6H4; C6H5; C6H5
9
1i: 4-MeC6H4; 4-BrC6H4; 2-BrC6H4; C6H5
1j: 4-MeC6H4; C6H5; 4-CNC6H4; C6H5
1k: 4-MeC6H4; C6H5; 4-MeOC6H4; C6H5
1l: 4-MeC6H4; 4-BrC6H4; 4-NO2C6H4; C6H5
82% (2i)
85% (2j)
75% (2k)
79% (2l)
10
11
12
13
14
15
16
1m: 4-MeC6H4; C6H5; 1-naphthyl; C6H5
1n: 4-MeC6H4; C6H5; 1-naphthyl; C6H5
1o:4-MeC6H4; C6H5; 2-thiophenyl; C6H5
1p: 4-MeC6H4; C6H5; C6H5; n-C4H9
65% (2m)
68% (2n)
51% (2o)
67% (2p)
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Table 2. (Continued)
Entry
Substrates 1: R1; R2; R3; R4
Products 2
Yield[b]
17
1q: 4-MeC6H4; C6H5; C6H5; cyclopropanyl
55% (2q)
18
19
20
1r: Me; C6H5; C6H5; C6H5
1s: 4-MeC6H4; C6H5; C6H5; H
1t: 4-MeC6H4; H; C6H5; C6H5
48% (2r)
complex
n.r.[c]
21
75%[d] (2w)
[a]
Conditions: substrates 1 (0.5 mmol), PhMe (2 mL), [CuPPh3I]4 (46 mg, 0.025 mmol), reflux.
Isolated yields.
n.r.=no reaction.
[CuPPh3I]4 (91 mg, 0.05 mmol).
[b]
[c]
[d]
Scheme 2. Crossover experiment of 1a and 1g.
not occur under normal conditions.[17] Notably, start-
ing from 1w, we could finally obtain a symmetrical
oligomer 2w containing two 2-sulfonylbuta-1,3-diene
moieties. The structure of product 2i was unambigu-
ously demonstrated by X-ray diffraction analysis
(Figure 1, also see the Supporting Information).[18]
In order to figure out whether the migration of the
sulfonyl group occurred in an intramolecular or inter-
molecular pathway, we performed a crossover experi-
ment between equimolar amounts of 1a and 1g yield-
ing the corresponding products 2a and 2g in 48% and
33% yields, respectively, and the crossover products
2c and 2x in 42% and 47% yields, respectively
(Scheme 2, determined by HPLC). This result clearly
indicated that migration of the sulfonyl group pro-
ceeds in an intermolecular manner. It was noteworthy
that the sulfonyl groups were introducted to the sp2-
carbon straightforwardly with excellent stereoselectiv-
Scheme 3. Proposed mechanism.
ity. The migration was triggered most likely by the re- First, a 6-endo-dig addition of sulfonohydrazone onto
lease of nitrogen. the copper(I)-alkyne complex A resulted in the for-
As a working hypothesis, we proposed the follow- mation of intermediate B, which collapsed into the al-
ing mechanism based on our observation for the for- lenic intermediate C. The unstable intermediate C de-
mation of (1E,3E)-2-sulfonyl-1,3-dienes (Scheme 3). composed to nitrogen and ion pairs D. Then, a nucleo-
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Copper(I)-Catalyzed Stereoselective Synthesis of (1E,3E)-2-Sulfonyl-1,3-dienes
Wang, G. Zhang, L. Zhang, Synlett 2010, 692–706; d) K.
philic attack of the tosyl anion to the central sp
carbon atom of the hypothetical allenic moiety
carbon followed by electron transfer gave the product
2. As we surmised, no (1E,3Z)-2-sulfonyl-1,3-dienes
were observed due to the sterically hindered effect
between the tosyl anion and R3. Intermolecular trap-
ping with external nucleophiles such as ethanol and
aniline has been tested. The desired product was not
obtained.
In summary, a facile approach for the stereoselec-
tive synthesis of highly substituted (1E,3E)-2-sulfonyl-
1,3-dienes from N-propargylic sulfonohydrazone de-
rivatives has been developed. A key feature of the re-
arrangement was that it allowed the straightforward
introduction of sulfonyl groups to alkene units. Stud-
ies aiming at exploring mechanistic aspects of this re-
action and developing further transformations of N-
propargylic sulfonohydrazone derivatives are ongoing.
Majumdar, T. Bhattacharyya, B. Chattopadhyay, B.
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General Procedure for Synthesis of N-Propargylic
Hydrazones
ˇ
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To a solution of propargylic acetate (5 mmol) and hydrazone
(6 mmol) in CH3CN (20 mL), FeCl3 (0.5 mmol) was added
and the mixture was stirred at room temperature. When the
reaction was completed (monitored by TLC), the solvent
was removed under vacuum, and then the residue was fur-
ther purified by silica gel column chromatography (petrole-
um ether and ethyl acetate) to afford the desired N-propar-
gylic hydrazones.
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General Procedure for the Synthesis of (1E,3E)-1,3-
Dienes
ACHTUNGTRENNUNG[CuPPh3I]4 (5 mol%), propargylic hydrazone 1 (0.5 mmol)
was suspended in anhydrous toluene (2 mL) in a 10-mL
Schlenk tube under nitrogen. The resulting solution was
stirred at reflux until reaction was completed (monitored by
TLC). After cooling to room temperature, the solvent was
removed under vacuum. The residue was purified by
column chromatography (petroleum ether:ethyl acetate=
20:1).
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Mapp, Org. Lett. 2010, 12, 2574–2577.
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Eur. J. 2007, 13, 9686–9702; b) Y. T. Lee, Y. K. Chung,
J. Org. Chem. 2008, 73, 4698–4701; c) Z. Jiang, P. Lu, Y.
Wang, Org. Lett. 2012, 14, 6266–6269.
Acknowledgements
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Financial support from National Natural Science Foundation
of China (No. 21072159 and 21272190) and PCSIRT in Uni-
versity is gratefully acknowledged.
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Copper(I)-Catalyzed Stereoselective Synthesis of (1E,3E)-2-
Sulfonyl-1,3-dienes from N-Propargylic Sulfonohydrazones
7
Adv. Synth. Catal. 2013, 355, 1 – 7
Yu Zhu, Hai-Tao Tang, Zhuang-Ping Zhan*
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