Tandem reaction of α-hypervalent iodo functionalized phosphonium and arsonium ylides as umpolung reagents

Article abstract of DOI:10.1016/S0040-4039(02)01503-4

α-Hypervalent iodo functionalized phosphonium and arsonium ylides 2 can be used as umpolung ylides to react with nucleophiles to give α-heteroatom substituted ylides 4 in good yields. A tandem sequence of nucleophilic substitution then Wittig reaction occ

Full text of DOI:10.1016/S0040-4039(02)01503-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 6823–6825
Tandem reaction of a-hypervalent iodo functionalized
phosphonium and arsonium ylides as umpolung reagents
Zhi-Zhen Huang, Xiao-Chun Yu and Xian Huang*
Department of Chemistry, Zhejiang University, Hangzhou, 310028, State Key Laboratory of Organoelemental Chemistry,
Nankai University, Tianjin 300071, China
Received 28 March 2002; revised 23 May 2002; accepted 19 July 2002
Abstract—a-Hypervalent iodo functionalized phosphonium and arsonium ylides 2 can be used as umpolung ylides to react with
nucleophiles to give a-heteroatom substituted ylides 4 in good yields. A tandem sequence of nucleophilic substitution then Wittig
reaction occurs smoothly to form (Z)-a-halo-a,b-unsaturated esters 6, stereoselectively, in moderate to excellent yields. © 2002
Elsevier Science Ltd. All rights reserved.
Since its discovery, the Wittig reaction has remained
one of the primary methods for the formation of car-
bonꢀcarbon double bonds and is widely used in the
synthesis of natural products.1–3 Research on a-het-
eroatom substituted ylides is a very important aspect in
ylide chemistry. Through the Wittig reaction of a-het-
eroatom substituted ylides, carbonꢀcarbon double
bonds can be formed and heteroatoms can be readily
introduced to a-position at the same time.3–7 In general,
electrophiles react with ylides and this is the basis for
the synthesis of a-heteroatom substituted ylides. How-
ever, many electrophiles reacted with ylides are often
unstable or difficult to prepare or handle. We consid-
ered whether it would be possible to reverse the polarity
of the a-carbon in ylides and enable the umpolung ylide
to react with a nucleophile, explore and simplify the
methods for the synthesis of a-heteroatom substituted
ylides and develop ylide chemistry as well.
reverse the polarity of the a-carbon in an ylide.
Although the synthesis of a- hypervalent iodo function-
alized phosphonium ylides has been previously
reported,9 their application has not been demonstrated
until now. Using a similar protocol, we synthesized the
new a-hypervalent iodo functionalized arsonium ylide 2
in a yield of 82% (Scheme 1).
As expected, the polarity of the a-carbon in phospho-
nium and arsonium ylides 2 has been reversed and they
can be reacted with nucleophiles 3, such as, the bro-
mide, thiophenyl and phenylselenenyl anions (see Table
1). This nucleophilic substitution reaction has the
advantages of simpler manipulation and mild reaction
conditions over the previous electrophilic protocols,
and gives the corresponding a-heteroatom substituted
ylides 4 in good yields (Scheme 2).
Compared with their precursors, the nucleophilicity of
the phosphonium or arsonium ylides 2 has been
decreased dramatically. Experiments showed that phos-
phonium or arsonium ylides 2 do not undergo the
Wittig reaction with benzaldehyde. Therefore, we added
Recently, hypervalent iodides have been increasingly
used in organic synthesis.8 When a hypervalent iodo
group is linked to an unsaturated carbonꢀcarbon bond,
the carbon can be attacked by nucleophiles. In view of
this we tried to utilize a hypervalent iodo group to
Scheme 1.
Keywords: umpolung reagent; nucleophilic substitution; Wittig reaction; tandem reaction; synthesis.
* Corresponding author. Fax: 86-571-88807077; e-mail: huangx@mail.hz.zj.cn
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01503-4

6824
Z.-Z. Huang et al. / Tetrahedron Letters 43 (2002) 6823–6825
Table 1. Nucleophilic substitution reactions of ylides 2
tively, in moderate to excellent yields via the umpolung
ylides 2. Compared with the previous method, the
synthesis is simpler and yields are higher. The discovery
of umpolung ylides 2 should enrich ylide chemistry.
Further research on the application of this type of
umpolung ylides in organic synthesis is in progress now.
E
R
NuM
Yield of 4 (%)a
P
P
P
As
As
As
C2H5
C2H5
C2H5
CH3
C2H5
CH3
C6H5SH
84
85
81
86
80
70
C6H5SeNa
n-Bu4NBr
C6H5SH
4-CH3C6H4SH
C6H5SeNa
Acknowledgements
1
a The structures of the products were confirmed by H NMR, IR and
MS spectroscopy.
We thank the National Natural Science Foundation of
China for its financial support of the project 29972036.
COOR
Nu
-
Nu M+
COOR
+
IAr BF4
Ph3E = C
Ph3E = C
-
References
3
4
2
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863–927.
E = P, As
NuM = n-Bu4NBr, PhSNa, PhSeNa
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Scheme 2.
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the aldehydes 5 to the reaction mixture of phospho-
nium or arsonium ylides 2 with the nucleophiles. Fortu-
nately, the tandem nucleophilic substitution–Wittig
reaction can be carried out smoothly to form the
desired (Z)-a-halo-a,b-unsaturated esters 6 stereoselec-
tively.10 The yields of the tandem reaction are higher
than that of two-step reactions of substitution and
Wittig reaction (Scheme 3, Table 2).
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In conclusion, this new type of tandem reaction can
afford (Z)-a-halo-a,b-unsaturated esters 6, stereoselec-
9. Rorber, M. M.; Indra, P.; Wade, A. F. J. Am. Chem. Soc.
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Scheme 3.
Table 2. Tandem reaction of umpolung ylides 2 to give alkenes 6
E
NuM
R
R1
Yielda (%)
Z/Eb
P
P
P
P
P
P
As
As
As
n-Bu4NCl
n-Bu4NCl
n-Bu4NBr
n-Bu4NBr
n-Bu4NBr
n-Bu4NI
n-Bu4NBr
n-Bu4NBr
n-Bu4NI
C2H5
C2H5
C2H5
C2H5
C2H5
C2H5
CH3
4-ClC6H4
93
55
97
92
60
87
81
74
75
85/15
89/11
86/14
91/9
89/11
83/17
91/9
CH3CH2CH2
4-NO2C6H4
4-FC6H4
CH3CH2CH2
4-CH3OC6H4
4-Cl2C6H4
4-NO2C6H4
4-ClC6H4
CH3
CH3
85/15
90/10
a The structures of the products were confirmed by 1H NMR, IR and MS spectroscopy.
b The Z/E ratios were determined by 1H NMR or GC. The 1H NMR spectra of the known a-halo-a,b-unsaturated esters and empirical formulae
show that the chemical shift of the vinyl proton in (Z)-a-halo-a,b-unsaturated ester is larger than that of the E-isomer. For example, the
chemical shifts of the vinyl protons in ethyl (Z)- and (E)-a-bromocinnamate are 8.13 and 7.37 ppm, respectively.11 Thus, we assigned the
configuration of the a-halo-a,b-unsaturated esters 6 by the comparison of the 1H NMR data with known 1H NMR data12 or empirical formulae.

Z.-Z. Huang et al. / Tetrahedron Letters 43 (2002) 6823–6825
6825
10. Tandem reaction of umpoled ylides 2 for the stereoselective
synthesis of (Z)-a-halo-a,b-unsaturated esters 6: The mix-
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11. (a) Kopping, B.; Chatgillialoglu, C.; Zehnder, M.; Giese,
B. J. Org. Chem. 1992, 57, 3994–4000; (b) Bellina, F.;
Carpita, A.; Santis, M.; Rossi, R. Tetrahedron 1994, 50,
12029–12046.
arsonium ylides
2 (2 mmol), tetrabutylammonium
halide 3 (2 mmol) and aldehyde 5 (2 mmol) in CH2Cl2 (20
ml) was stirred at room temperature for 8–48 h. After the
reaction was complete, the organic phase was washed with
water (10 ml×2) and dried over magnesium sulfate. After
evaporation of the solvent, the crude product was purified
by preparative TLC (silica gel, hexane–ethyl acetate as
12. (a) Huang, Y. Z.; Shi, L. L.; Li, S. W.; Huang, R. Synth.
Commun. 1989, 19, 2639–2646; (b) Zheng, Q. G.; Fu, W.
Y.; Chen, B. C.; Huang, X. Youji Huaxue 1988, 8, 661–664;
(c) Huang, Z. Z.; Wu, L. L.; Zhu, L. L.; Huang, X. Synth.
Commun. 1996, 26, 677–682.