Triphenylphosphine-mediated olefination of aldehydes with (Z)-(2- acetoxyalk-1-enyl)phenyl-λ3-iodanes: Generation and reaction of (2- oxoalkyl)phenyl-λ3-iodanes

Article abstract of DOI:10.1039/b003090m

(Z)-(2-Acetoxyalk-1-enyl)phenyl-λ³-iodanes, on treatment with triethylamine in methanol in the presence of triphenylphosphine, undergo Wittig olefination with aldehydes, which involves the intermediacy of α- iodanyl ketones generated by in situ

Full text of DOI:10.1039/b003090m

Triphenylphosphine-mediated olefination of aldehydes with
(Z)-(2-acetoxyalk-1-enyl)phenyl-l3-iodanes: generation and reaction of
(2-oxoalkyl)phenyl-l3-iodanes
Masahito Ochiai,* Yoshio Nishi, Junichi Nishitani, Da-Wei Chen, Sakiko Hashimoto and Yoshimi Tsuchimoto
Faculty of Pharmaceutical Sciences, University of Tokushima, 1-78 Shomachi, Tokushima 770-8505, Japan.
E-mail: mochiai@ph2.tokushima-u.ac.jp
Received (in Cambridge, UK) 17th April 2000, Accepted 22nd May 2000
(Z)-(2-Acetoxyalk-1-enyl)phenyl-l3-iodanes, on treatment
with triethylamine in methanol in the presence of triphenyl-
phosphine, undergo Wittig olefination with aldehydes,
which involves the intermediacy of a-iodanyl ketones
generated by in situ protonation of monocarbonyl iodonium
ylides.
(E)- and (Z)-1-phenylundec-1-en-3-one 5c in 73% yield. No
evidence for formation of the epoxide 3 (R = C8H17, RA = Ph)
was observed in this reaction. The results of the Wittig type
3
reaction of aldehydes with the vinyl(phenyl)-l -iodanes 1 are
3
summarized in Table 1. The vinyl-l -iodanes 1a–c readily
undergo Wittig olefinations with aromatic aldehydes containing
electron-withdrawing or -donating substituents as well as with
aliphatic aldehydes to give a,b-unsaturated ketones 5 with high
trans selectivity. With a,b-unsaturated aldehydes, selective
reaction at the carbonyl group was observed with no evidence
for Michael addition yielding cyclopropanes (entries 9 and 16).
Recently, we reported that the ester exchange reaction of (Z)-
3
(2-acetoxyalk-1-enyl)phenyl-l -iodanes 1 with EtOLi quantita-
tively generates the unstabilized monocarbonyl iodonium ylides
2 in THF at 278 °C with the liberation of ethyl acetate (Scheme
1).1 In a marked contrast to the stable iodonium ylides derived
from b-dicarbonyl compounds,2 the monocarbonyl iodonium
ylides 2 are moderately nucleophilic and undergo nucleophilic
attack towards carbonyl compounds and activated imines. In
general, ylides react with carbonyl compounds in either of two
possible reaction modes, Wittig type reaction yielding alkenes
and Corey type reaction leading to the formation of epoxides,
depending on the nature of ylides and carbonyl compounds.3
3
With the use of the sterically demanding l -iodane, b-tert-
butylvinyliodane 1d, the Wittig olefination becomes sluggish
(entry 17).
3
Table 1 Wittig olefinations of aldehydes with b-acetoxyvinyl(phenyl)-l -
iodanes 1a
Product (yield (%))b
3
Entry
1
RACHO (RA)
t/h
5
Ratioc
Because of the very high reductive nucleofugality of the l -
phenyliodanyl groups,4 monocarbonyl iodonium ylides 2
exclusively undergo alkylidene transfer reactions (Corey type)
with aldehydes yielding epoxides:1a thus, the reaction of 1 with
aldehydes in the presence of EtOLi gives a,b-epoxy ketones 3
in good yields with trans-isomers as the major product. No
formation of the Wittig type olefination products 5 was
observed in this reaction. The reaction course, however, was
dramatically altered to the Wittig olefination pathway, when
both the base and the solvent were changed to triethylamine and
methanol, and the reaction was carried out in the presence of
triphenylphosphine. We report herein triphenylphosphine-
mediated Wittig olefination of aldehydes with (Z)-(2-acetox-
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1a
1a
1b
1b
1b
1b
1b
1b
1b
1c
1c
1c
1c
1c
1c
1c
1d
Ph
n-C9H19
Ph
p-MeOC6H4
p-MeC6H4
p-ClC6H4
p-NO2C6H4
n-C9H19
E-MeCHNCH 42d
Ph
p-MeC6H4
p-MeOC6H4
p-ClC6H4
p-NO2C6H4
n-C9H19
24d
48d
24
24
24
24d
40d
48
5a (62)
5b (60)
5c (73)
5d (45)
5e (64)
5f (85)
5g (86)
5h (65)
5i (57)
5j (58)
5k (62)
5l (75)
5m (60)
5n (82)
5o (53)
5p (48)
5q (10)
93+7
100+0
98+2
99+1
99+1
91+9
93+7
100+0
100+0
92+8
24
24
24
24
24
24
100+0
95+5
99+1
> 99+1
100+0
100+0
99+1
3
yalk-1-enyl)phenyl-l -iodanes 1, which involves an efficient
3
generation of (2-oxoalkyl)phenyl-l -iodanes 4 under mild
conditions.
E-MeCHNCH 24
p-ClC6H4 24
a Reactions were carried out at 60 °C under N2. b Isolated yields. c Trans+cis
ratio. d Reactions were carried out at 25 °C under N2.
As illustrated in Scheme 2, a mechanism for the Wittig
olefination of aldehydes upon reaction with (Z)-(2-acetoxyalk-
3
1-enyl)-l -iodanes 1 in the presence of triethylamine and
triphenylphosphine in MeOH might be assumed to involve the
3
following key steps: (i) ester exchange of b-acetoxyvinyl-l -
iodanes 1 with MeOH under basic conditions generating the
monocarbonyl iodonium ylides 2 with the liberation of methyl
acetate, (ii) formation of (2-oxoalkyl)-l -iodanes 4 via protona-
3
Scheme 1
tion of the ylides 2 with the resulting Et3NHBF4, (iii)
bimolecular nucleophilic substitution of 4 with triphenylphos-
phine yielding (2-oxoalkyl)phosphonium salts 6, and (iv) Wittig
olefination of aldehydes with b-acylphosphonium ylides 7
produced from 6 by reaction with regenerated triethylamine.
This mechanism involves the in situ generation and conversion
of the monocarbonyl iodonium ylides 2 which undergo Corey
type reaction to the monocarbonyl phosphonium ylides 7 which
3
To a stirred solution of (Z)-2-acetoxydec-1-enyl(phenyl)-l -
iodane 1b and triphenylphosphine (2 equiv.) in MeOH was
added triethylamine (1.3 equiv.) at room temperature under
nitrogen and the mixture was stirred for 30 min. A solution of
benzaldehyde (1.5 equiv.) in MeOH was added and the mixture
was heated at 60 °C for 24 h. After usual workup, preparative
TLC [hexane–ethyl acetate (10+1)] afforded a 98+2 mixture of
DOI: 10.1039/b003090m
Chem. Commun., 2000, 1157–1158
This journal is © The Royal Society of Chemistry 2000
1157

by eight orders of magnitude.6 Based on these data, the acidity
(pKa) of a-methylene protons of (2-oxoalkyl)iodanes 4 is
estimated to be ca. 12. Therefore, it seems reasonable to assume
that Et3NHBF4 with similar acidity (pKa = 11.0),7 undergoes
proton transfer to the monocarbonyl iodonium ylides 2 yielding
the (2-oxoalkyl)iodanes 4.
It is possible to isolate the intermediate (2-oxoalkyl)phos-
phonium salts 6: treatment of 1b with triethylamine and
triphenylphosphine in MeOH at room temperature, after
acidification of the reaction mixture with 5% aqueous HBF4
solution, afforded the phosphonium tetrafluoroborate 6b in 89%
yield. Without acid treatment, the monocarbonyl phosphonium
ylide 7b was obtained, thereby illustrating the occurrence of
transylidation between iodonium and phosphonoim ylides
under such conditions. The formation of phosphonium ylides 7
is compatible with the reported acidity of acetonyl(triphenyl)-
phosphonium salt 6a (R = Me, pKa = 6.6), i.e. more acidic than
Et3NHBF4.8
In conclusion, we have developed an efficient one-pot
procedure for Wittig olefination of aldehydes with (Z)-
Scheme 2
3
(2-acetoxyalk-1-enyl)phenyl-l -iodanes 1. In addition to the
undergo Wittig olefination. Alternatively, the (2-oxo-
alkyl)iodanes 4 might be directly produced via triethylamine-
mediated ester exchange of vinyliodanes 1 with MeOH.
reported Corey type alkylidene-transfer reaction of the mono-
carbonyl iodonium ylides to aldehydes, this new strategy
3
developed here makes vinyl-l -iodanes 1 valuable progenitors
Several experimental observations are in line with this
proposed mechanism. Reaction of 1b with triethylamine (1.1
equiv.) in MeOH (25 °C, 1 h) afforded a mixture of a-methoxy
ketone 8 (43%), hydroxy dimethylacetal 9 (35%) and methyl
acetate (91%) (Scheme 3). Without triethylamine, 1b was
recovered unchanged in MeOH. High yield formation of methyl
acetate clearly indicates the intervention of the ester exchange
between b-acetoxyvinyliodane 1b and MeOH under basic
conditions. Bimolecular nucleophilic substitution of (2-oxo-
alkyl)iodane 4b with MeOH will produce the a-methoxy ketone
8. Furthermore, formation of the hydroxy dimethylacetal 9
under basic conditions strongly suggests the intermediacy of the
(2-oxoalkyl)iodane 4b in this reaction (Scheme 3), as reported
by Moriarty et al.5 It has been reported that the presence of the
in monocarbonyl onium ylide chemistry.
Notes and references
1 (a) M. Ochiai, Y. Kitagawa and S. Yamamoto, J. Am. Chem. Soc., 1997,
119, 11598; (b) M. Ochiai and Y. Kitagawa, Tetrahedron Lett., 1998, 39,
5569; (c) M. Ochiai and Y. Kitagawa, J. Org. Chem., 1999, 64, 3181.
2 G. F. Koser, in The Chemistry of Functional Groups, Supplement D,
Wiley, New York, 1983; A. Varvoglis, The Organic Chemistry of
Polycoordinated Iodine, VCH, New York, 1992; P. J. Stang and V. V.
Zhdankin, Chem. Rev., 1996, 96, 1123.
3 T. Naito, S. Nagase and H. Yamataka, J. Am. Chem. Soc., 1994, 116,
10080; Y. Matano, J. Chem. Soc., Perkin Trans. 1, 1994, 2703; B. E.
Maryanoff and A. B. Reitz, Chem. Rev., 1989, 89, 863; A. W. Johnson,
W. C. Kaska, K. A. O. Starzewski and D. A. Dixon, Ylides and Imines of
Phosphorus, Wiley, New York, 1993; B. M. Trost and L. S. Melvin,
Sulfur Ylides, Academic Press, New York, 1975; S. Oae, Organic
Chemistry of Sulfur, Plenum, New York, 1977.
3
l -phenyliodanyl group raises the CH acidity of malonic esters
4 T. Okuyama, T. Takino, T. Sueda and M. Ochiai, J. Am. Chem. Soc.,
1995, 117, 3360.
5 R. M. Moriarty, H. Hu and S. C. Gupta, Tetrahedron Lett., 1981, 22,
1283; R. M. Moriarty and O. Prakash, Acc. Chem. Res., 1986, 19, 244.
6 O. Y. Neiland and B. Y. Karele, Zh. Org. Khim., 1971, 7, 1611.
7 D. R. Lide, CRC Handbook of Chemistry and Physics, CRC, Boca Raton,
FL, 1992.
8 S. Fliszar, R. F. Hudson and G. Salvadori, Helv. Chim. Acta, 1963, 46,
1580; A. W. Johnson and R. T. Amel, Can. J. Chem., 1968, 46, 461.
Scheme 3
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Chem. Commun., 2000, 1157–1158