Reaction of unstabilized iodonium ylides with organoboranes

Article abstract of DOI:10.1021/ol0495669

Exposure of monocarbonyl iodonium ylides, generated by the ester exchange of (Z)-(2-acetoxyvinyl)-λ³-iodanes with EtOLi, to organoboranes results in a 1,2-shift of a carbon ligand from boron to the ylide carbons, which probably generates hitherto uncharacterized α-boryl ketones.

Full text of DOI:10.1021/ol0495669

ORGANIC
LETTERS
2004
Vol. 6, No. 9
1505-1508
Reaction of Unstabilized Iodonium
Ylides with Organoboranes
Masahito Ochiai,* Yoshimi Tuchimoto, and Nobuyuki Higashiura
Faculty of Pharmaceutical Sciences, UniVersity of Tokushima, 1-78 Shomachi,
Tokushima 770-8505, Japan
mochiai@ph.tokushima-u.ac.jp
Received March 9, 2004
ABSTRACT
Exposure of monocarbonyl iodonium ylides, generated by the ester exchange of (Z)-(2-acetoxyvinyl)-λ3-iodanes with EtOLi, to organoboranes
results in a 1,2-shift of a carbon ligand from boron to the ylide carbons, which probably generates hitherto uncharacterized r-boryl ketones.
Onium ylides react with organoboranes and transfer a carbon
ligand on boron to ylide carbanions via the intermediate
formation of zwitterionic organoborane-ylide complexes.
Group 15 (N, P, As) and 16 (S) onium methylides react with
organoboranes to afford the corresponding homologated
boranes.1 Reaction of ethyl (dimethylsulfuranylidene)acetate
with triphenylborane gives, after alkaline hydrolysis, ethyl
phenylacetate in high yields.1b Recently, Shea and co-workers
developed an efficient boron-catalyzed polymerization of
dimethylsulfoxonium methylide yielding R-hydroxy poly-
methylene and block copolymers through living polyho-
mologations.2
shift from boron to nitrogen in the reaction of [(N-
tosylimino)iodo]benzene PhIdNTs with trialkylboranes.4 We
are pleased to report herein the reaction of iodonium ylides
with organoboranes, in which unstabilized monocarbonyl
iodonium ylides 5 smoothly undergo a 1,2-shift of an alkyl
or an aryl group from boron to ylide carbons under mild
conditions. In marked contrast, no reaction was observed
between stabilized iodonium ylides 1 and organoboranes.
â-Dicarbonyl and â-disulfonyl iodonium ylides, relatively
stable species, enjoy rich chemistry in modern organic
synthesis and serve as useful progenitors for the generation
of carbenes.3,5 The attempted reaction of the stable ylides 1
with triorganoboranes such as Ph3B and Et3B (THF/rt) did
not show any evidence for formation of carbon ligand transfer
product 3 but instead gave a small amount of O-phenylated
ether 2 (Scheme 1). Formation of the enol ether 2 involves
the well-known thermal 1,4-rearrangement with phenyl
migration from iodine(III) to oxygen atom, which proceeds
via the intermediacy of a spiro-Meisenheimer complex.6 The
stable â-dicarbonyl ylides 1 possess a highly delocalized
On the other hand, reactions of group 17 onium ylides,
especially iodonium ylides, with organoboranes are virtually
unexplored, despite their extensive synthetic use in organic
synthesis.3 Dai and Yang reported an interesting alkyl group
(1) (a) Tufariello, J. J.; Lee, L. T. C. J. Am. Chem. Soc. 1966, 88, 4757.
(b) Tufariello, J. J.; Lee, L. T. C.; Wojtkowski, P. J. Am. Chem. Soc. 1967,
89, 6804. (c) Musker, W. K.; Stevens, R. R. Tetrahedron Lett. 1967, 995.
(d) Koster, R.; Rickborn, B. J. Am. Chem. Soc. 1967, 89, 2782.
(2) (a) Shea, K. J.; Walker, J. W.; Zhu, H.; Paz, M.; Greaves, J. J. Am.
Chem. Soc. 1997, 119, 9049. (b) Busch, B. B.; Paz, M. M.; Shea, K. J.;
Staiger, C. L.; Stoddard, J. M.; Walker, J. R.; Zhou, X.-Z.; Zhu, H. J. Am.
Chem. Soc. 2002, 124, 3636.
(3) (a) Koser, G. F. In The Chemistry of Functional Groups, Supplement
D; Wiley: New York, 1983; Chapter 18. (b) Varvoglis, A. Synthesis 1984,
709. (c) Moriarty, R. M.; Vaid, R. K. Synthesis 1990, 431. (d) Varvoglis,
A. The Organic Chemistry of Polycoordinated Iodine; VCH: New York,
1992. (e) Zhdankin, V. V.; Stang, P. J. Chem. ReV. 2002, 102, 2523.
(4) Yang, R.-Y.; Dai, L.-X. Synthesis 1993, 481.
(5) (a) Moriarty, R. M.; Prakash, O.; Vaid, R. K.; Zhao, L. J. Am. Chem.
Soc. 1989, 111, 6443. (b) Hadjiarapoglou, L.; Spyroudis, S.; Varvoglis, A.
J. Am. Chem. Soc. 1985, 107, 7178. (c) Moriarty, R. M.; Bailey, B. R.;
Prakash, O.; Prakash, I. J. Am. Chem. Soc. 1985, 107, 1375. (d) Muller, P.;
Fernandez, D. HelV. Chim. Acta 1995, 78, 947.
(6) Takaku, M.; Hayashi, Y.; Nozaki, H. Tetrahedron 1970, 26, 1243.
10.1021/ol0495669 CCC: $27.50 © 2004 American Chemical Society
Published on Web 04/06/2004

Scheme 1
Table 1. Reaction of Monocarbonyl Iodonium Ylides 5 with
Organoboranesa
entry
λ3-iodane 4
borane
Et3B
n-Bu3B
s-Bu3B
(c-C5H9)3B
(c-C5H9)3B
(c-C6H11)3B
[Ph(CH2)2]3B
Ph3B
(p-MeC6H4)3B
Ph3B
n-Bu3B
ketone 6
yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
4a
4a
4a
4a
4a
4a
4a
4a
4a
4b
4c
4c
4d
6a
6b
6c
6d
6d
6e
6f
6g
6h
6g
6i
86c
68 (72)c
76
96
15d
74
67
67
50
73
73
69
62c
ylidic carbanion directly bound to the strongly electron-
withdrawing phenyliodonio group.7 Consequently, they
exhibit relatively low nucleophilicity, which in turn renders
these ylides inactive toward organoboranes.
Recently, we found that the ester exchange reaction
between (Z)-(2-acetoxyvinyl)-λ3-iodanes 4 and EtOLi re-
sulted in quantitative generation of the unstable monocar-
bonyl iodonium ylides 5 in THF at -78 °C, with the
liberation of ethyl acetate (Scheme 2).8 In contrast to the
(c-C5H9)3B
n-Bu3B
6j
6k
a Reaction was carried out using 1.3 equiv of an organoborane in THF
at -78 °C for 1 h and then at room temperature for 0.5 h under argon.
b Isolated yields. c GC yields. d With use of organoborane (0.33 equiv).
In the Brown group, 9-borabicyclo[3.3.1]nonane (9-BBN)
is used as a nonmigrating blocking group on tetrasubstituted
borate complexes, for instance, in the R-alkylation of
R-bromo ketones and esters.11 The reaction of monocarbonyl
iodonium ylide 5a with B-cyclopentyl-9-BBN, however,
resulted in an exclusive migration of the cyclooctyl-boron
bond rather than the desired cyclopentyl-boron bond to give
the hydroxy ketone 7 in 51% yield (Scheme 3). With
Scheme 2
Scheme 3
stabilized iodonium ylides 1, the monocarbonyl iodonium
ylides 5 are moderately nucleophilic in nature and act as
alkylidene transfer agents to carbonyl compounds and
activated imines to yield R,â-epoxy ketones and 2-acylaziri-
dines stereoselectively in good yields.9 The ylides 5 undergo
transfer of a carbon ligand from boron to ylide carbons by
the reaction with triorganoboranes. Thus, exposure of the
monocarbonyl iodonium ylide 5a (R ) n-C8H17), derived in
situ from (Z)-(2-acetoxyvinyl)-λ3-iodane 4a by ester ex-
change with EtOLi (1.3 equiv) in THF at -78 °C for 10-
20 min, to Et3B (1.3 equiv) at -78 °C for 1 h and then at
room temperature for 0.5 h under argon afforded ethylated
ketone 6a in 86% yield (Table 1, entry 1).10 Secondary alkyl
and aryl groups are also transferred from boron to ylide
carbons. Comparison of the results of entries 4 and 5 in Table
1 indicates that only one alkyl group in the trialkylborane is
active in the reaction. With use of triethylaluminum instead
of Et3B, ketone 6a was obtained in 46% yield.
B-cyclohexyl- and B-n-hexyl-9-BBN, selective formation of
7 was also observed in 37 and 46% yields, respectively.12
Reaction of iodonium ylides 5 with catecholborane
undergoes the boron-to-carbon 1,2-shift of hydrogen to give
methyl ketones 8:1d thus, exposure of 5a to catecholborane
(10) Experimental Procedure. 6a (Table 1, entry 1): To a stirred
solution of (Z)-(2-acetoxy-1-decenyl)(phenyl)(tetrafluoroborato)-λ3-iodane
(4a)8 (37 mg, 0.075 mmol) in THF (3.7 mL) was added a 0.58 M THF
solution of EtOLi (0.167 mL, 0.097 mmol) at -78 °C under argon, and the
mixture was stirred for 20 min. After addition of a 1.06 M hexane solution
of Et3B (0.92 mL, 0.097 mmol), the mixture was stirred for 1 h at -78 °C
and 0.5 h at room temperature. The reaction mixture was quenched with
water and extracted with dichloromethane. The organic phase was washed
with brine and dried over anhydrous Na2SO4. The yield of 6a was
determined by GC analysis using an FFS ULBON HR-1 capillary column
(0.25 mm × 50 m).
(7) For the Hammett substituent constant (σp ) 1.37) of Ph(BF4)I-,
see: Mironova, A. A.; Maletina, I. I.; Iksanova, S. V.; Orda, V. V.;
Yagupolskii, L. M. Zh. Org. Khim. 1989, 25, 306.
(8) Ochiai, M.; Kitagawa, Y.; Yamamoto, S. J. Am. Chem. Soc. 1997,
119, 11598.
(11) (a) Brown, H. C.; Rogic, M. M.; Nambu, H.; Rathke, M. W. J. Am.
Chem. Soc. 1969, 91, 2147. (b) Brown, H. C.; Nambu, H.; Rogic, M. M.
J. Am. Chem. Soc. 1969, 91, 6855. (c) Hara, S.; Kishimura, K.; Suzuki, A.
Tetrahedron Lett. 1978, 2891.
(9) (a) Ochiai, M.; Kitagawa, Y. Tetrahedron Lett. 1998, 39, 5569. (b)
Ochiai, M.; Kitagawa, Y. J. Org. Chem. 1999, 64, 3181. (c) Ochiai, M.;
Kitagawa, Y. J. Synth. Org. Chem. Jpn. 2000, 58, 1048.
(12) Reaction of B-n-hexyl-9-BBN with ethyl diazoacetate gives products
derived from exclusive B-cyclooctyl bond migration. See: Hooz, J.; Gunn,
D. M. Tetrahedron Lett. 1969, 3455.
1506
Org. Lett., Vol. 6, No. 9, 2004

(1.3 equiv) in THF afforded 2-decanone 8a in 66% yield
(Scheme 4). Similarly, ylide 5c gave 5-phenyl-2-pentanone
8b (61%).
CHOBMe2) by ca. 19 kcal/mol.17 Interestingly, Abiko and
Masamune reported the characterization of the intermediate
R-boryl esters in the double aldol reaction of acetate esters.18
Importantly, deuterium experiments showed that when the
reaction mixture of iodonium ylide 5a with n-Bu3B (-78
°C/1 h/THF) was quenched with MeOD at -78 °C, R-deu-
terated ketone 6b-Rd (59% D) was produced in 71% yield;
however, quenching with MeOD after warming the reaction
mixture to room temperature showed no deuterium incor-
poration in 6b (87% yield). Similar results were obtained in
the reaction with s-Bu3B. These results probably suggest the
involvement of the intermediate R-boryl ketone 10a (R )
n-C8H17, R′ ) n-Bu) under our conditions, which is thermally
unstable and easily decomposes to ketone 6b below room
temperature.19 Formation of O-boron enolates 12 via in-
tramolecular vinylic substitution of the zwitterions 11 or
through a 1,3-boron shift of 10 does not seem to occur,
because enolates 12 are known to be stable even at room
temperature.16,20
Scheme 4
The mechanism for the reaction of iodonium ylides 5 with
organoboranes, which involves formation of R-boryl ketones
10, is shown in Scheme 5. Initial formation of zwitterionic
Scheme 5
The temperature effects in the aldol condensations shown
in Table 2 further support the thermally unstable nature of
Table 2. Temperature Effects in One-Pot Aldol Condensationa
yield (%)b
conditions A
T (°C)/t (h)
ArCHO
(equiv)
entry
borane
13
6
1
2
3
4
5
6
7
n-Bu3B
n-Bu3B
n-Bu3B
n-Bu3B
n-Bu3B
s-Bu3B
-78/1
PhCHO (2)
56 (30:70)c 38
12 (51:49)c 26
-78/1, -30 PhCHO (2)
-78/1, 25
-78/1
-78/1, 25
-78/2
PhCHO (2)
0
68
ylide-borane complexes 9, followed by a rapid boron-to-
carbon 1,2-shift of an alkyl group with concomitant reductive
elimination of the hypernucleofuge, phenyliodonio group,13
produces R-boryl ketones 10. Subsequent hydrolysis affords
ketones 6. As an alternative process, formation of O-boron
zwitterions 11 and the further intramolecular nucleophilic
vinylic substitution14 yielding O-boron enolates 12 should
be considered; however, this pathway is not compatible with
our results (See below).
R-Boryl ketones have been proposed as intermediates in
some reactions but have never been characterized.15 At-
tempted synthesis of R-boryl ketones by the reaction of
R-diazo ketones with tripropylborane resulted in exclusive
formation of O-boron enolates.16 Ab initio molecular orbital
calculation shows that R-boryl ketone (Me2BCH2CHO) is
more unstable than the isomeric boron enolate (CH2d
m-ClC6H4CHO (2) 74 (50:50)c 38
m-ClC6H4CHO (2)
PhCHO (1.3)
PhCHO (1.3)
0
93
73 (50:50)c,d 16
62 (72:28)c 24
(c-C5H9)3B -78/2
a Reaction was carried out using 1.3 equiv of EtOLi and organoborane
in THF under argon. b Isolated yields. c Ratios of syn:anti. d Syn and anti
aldols are 65:35 and 50:50 mixtures of diastereoisomers, respectively.
R-boryl ketones 10. Treatment of a solution of R-boryl ketone
10a, generated by the reaction of ylide 5a with n-Bu3B at
-78 °C in THF, with benzaldehyde afforded a mixture of
aldol products 13 in 56% yields, while aldol condensation
after warming a solution of 10a to -30 °C dramatically
decreased the yield of 13 to 12% (Table 2, entry 2).21
Furthermore, no aldols 13 were produced when a solution
(17) Ibrahim, M. R.; Buhl, M.; Knab, R.; Schleyer, P. R. J. Comput.
Chem. 1992, 13, 1665.
(18) (a) Abiko, A.; Inoue, T.; Masamune, S. J. Am. Chem. Soc. 2002,
124, 10759. (b) Furuno, H.; Inoue, T.; Abiko, A. Tetrahedron Lett. 2002,
43, 8297. (c) Abiko, A. J. Synth. Org. Chem. Jpn. 2003, 61, 24.
(19) Attempted detection of R-boryl ketones 10 in THF-d8 by low-
temperature NMR experiments was fruitless.
(20) For Z-E isomerization of boron enolates, see: (a) Evans, D. A.;
Vogel, E.; Nelson, J. V. J. Am. Chem. Soc. 1979, 101, 6120. (b) Evans, D.
A.; Nelson, J. V.; Vogel, E.; Taber, T. R. J. Am. Chem. Soc. 1981, 103,
3099. (c) Masamune, S.; Mori, S.; Horn, D.; Brooks, D. W. Tetrahedron
Lett. 1979, 1665. (d) Boldrini, G. P.; Bortolotti, M.; Mancini, F.; Tagliavini,
E.; Trombini, C.; Umani-Ronchi, A. J. Org. Chem. 1991, 56, 5820.
(13) (a) Ochiai, M. In Chemistry of HyperValent Compounds; Akiba,
K., Ed.; Wiley-VCH: New York, 1999; p 359. (b) Okuyama, T.; Takino,
T.; Sueda, T.; Ochiai, M. J. Am. Chem. Soc. 1995, 117, 3360.
(14) For nucleophilic vinylic substitution of vinyl-λ3-iodanes, see: (a)
Ochiai, M.; Oshima, K.; Masaki, Y. J. Am. Chem. Soc. 1991, 113, 7059.
(b) Okuyama, T.; Takino, T.; Sato, K.; Ochiai, M. J. Am. Chem. Soc. 1998,
120, 2275. (c) Ochiai, M. J. Organomet. Chem. 2000, 611, 494.
(15) (a) Hooz, J.; Linke, S. J. Am. Chem. Soc. 1968, 90, 5936. (b) Brown,
H. C.; Rogic, M. M.; Rathke, M. W. J. Am. Chem. Soc. 1968, 90, 6218. (c)
Mukaiyama, T.; Murakami, M.; Oriyama, T.; Yamaguchi, M. Chem. Lett.
1981, 1193.
(16) Pasto, D. J.; Wojtkowski, P. W. Tetrahedron Lett. 1970, 215.
Org. Lett., Vol. 6, No. 9, 2004
1507

of 10a was warmed to room temperature prior to the aldol
condensations (Table 2, entries 3 and 5): in these cases, the
ketone 6b was obtained selectively in good yields.
ganoboranes. Most importantly, the reaction probably in-
volves in situ generation of hitherto uncharacterized R-boryl
ketones.
In conclusion, we have shown that, in contrast to the
stabilized iodonium ylides, the moderately nucleophilic
monocarbonyl iodonium ylides undergo transfer of a carbon
ligand from boron to ylide carbons by reaction with trior-
Acknowledgment. We wish to acknowledge financial
support in the form of a grant from the Ministry of Education,
Culture, Sports, Science and Technology of Japan.
Supporting Information Available: Detailed experi-
mental procedures and spectroscopic data. This material is
available free of charge via the Internet at http://pubs.acs.org.
(21) For stereochemical assignments of aldols, see: (a) Stiles, M.;
Winkler, R. R.; Chang, Y.; Traynor, L. J. Am. Chem. Soc. 1964, 86, 3337.
(b) House, H. O.; Crumrine, D. S.; Teranishi, A. Y.; Olmstead, H. D. J.
Am. Chem. Soc. 1973, 95, 3310. (c) Heathcock, C. H.; Davidsen, S. K.;
Hug, K. T.; Flippin, L. A. J. Org. Chem. 1986, 51, 3027.
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Org. Lett., Vol. 6, No. 9, 2004