Synthesis and characterization of β-haloalkenyl-λ3- bromanes: Stereoselective markovnikov addition of difluoro(aryl)- λ3-bromane to terminal acetylenes

Article abstract of DOI:10.1021/ja051690f

Reported here for the first time are the synthesis, isolation, and characterization of hypervalent β-haloalkenyl-λ³-bromanes. Exposure of terminal alkynes to p-trifluoromethylphenyl(difluoro)-λ³-bromane activated by BF₃-i-Pr₂O resulted in fluoro-λ³-bromanation of the triple bonds in a Markovnikov fashion, yielding (E)-β-fluoroalkenyl-λ³-bromanes stereoselectively in good yields. 5-Chloro-1-pentynes undergo domino λ³-bromanation-chlorine shift-fluorination or λ³-bromanation-chlorine shift-alkyl shift-fluorination reaction, depending on the substituents and afford (E)-β-chloroalkenyl-λ³-bromanes stereoselectively in high yields. The β-chloroalkenyl-λ³-bromanes contain three kinds of halogen atoms, F, Cl, and Br, in the molecule. Copyright

Full text of DOI:10.1021/ja051690f

Published on Web 07/07/2005
Synthesis and Characterization of â-Haloalkenyl-λ3-bromanes:
Stereoselective Markovnikov Addition of Difluoro(aryl)-λ3-bromane to
Terminal Acetylenes
Masahito Ochiai,*,† Yoshio Nishi,† Takeshi Mori,† Norihiro Tada,† Takashi Suefuji,† and
Hermann J. Frohn‡
Faculty of Pharmaceutical Sciences, UniVersity of Tokushima, 1-78 Shomachi, Tokushima 770-8505, Japan, and
Anorganische Chemie, UniVersitat Duisburg-Essen, Lotharstrasse 1, D-47048 Duisburg, Germany
Received March 17, 2005; E-mail: mochiai@ph.tokushima-u.ac.jp
Hypervalent 1-alkenyl(phenyl)-λ3-iodanes enjoy their rich chem-
Scheme 1
istry in modern organic synthesis.1 Because of the very high leaving
group ability of phenyl-λ3-iodanyl groups,2 they undergo unusual
vinylic SN2 displacement by the reaction with a wide range of
nucleophiles.3 They also serve as excellent progenitors for genera-
tion of alkylidene carbenes.4
In a marked contrast, little is known concerning the chemistry
of the closely related group 17 1-alkenyl-λ3-bromanes because a
Table 1. Addition of Difluoro-λ3-bromane 1 to 1-Decyne, Yielding
â-Fluorodecenyl-λ3-bromane 2aa
method for their syntheses is not available and no well-established
1-alkenyl-λ3-bromanes are known. In 1985, Olah and co-workers
reported the preparation of vinyl(methyl)(hexafluoroantimonato)-
λ3-bromane in chlorosulfonyl fluoride solution;5 alkylation of vinyl
bromide with a large excess of methyl fluoride-antimony pen-
tafluoride complex at -78 °C in SO2ClF afforded a light-yellow
colored solution of the vinyl(methyl)-λ3-bromane, whose 13C NMR
spectrum at -90 °C showed three absorptions at δ 132.9(Câ), 120.9
(CR), and 44.1(Me) ppm. The vinyl(methyl)-λ3-bromane was found
to be stable at -78 °C for only several hours (ca. 4 h), after which
polymerization sets in. We report herein, for the first time, the
synthesis, isolation, and characterization of â-fluoro- and â-chlo-
roalkenyl(aryl)-λ3-bromanes.
Recently, we reported the synthesis of 1-alkynyl(aryl)(tetrafluo-
roborato)-λ3-bromanes through ligand exchange of difluoro-λ3-
bromane 1 with 1-alkynylstannanes;6 thus, reaction of 1-(trimeth-
ylstannyl)-1-alkynes with p-trifluoromethylphenyl(difluoro)-λ3-
bromane (1) in the presence of BF3-Et2O at -78 °C in dichloro-
methane afforded 1-alkynyl(aryl)-λ3-bromanes in high yields. Use
of unsubstituted terminal alkynes instead of 1-alkynylstannanes,
however, dramatically changed the reaction course and resulted in
fluoro-λ3-bromanation of the triple bonds in a Markovnikov fashion,
yielding â-fluoroalkenyl-λ3-bromanes 2 (Scheme 1).
BF3
−
ROR
′
temp
C)
time
(h)
yield
(%)b
ratio
E:Z
entry
(equiv)
solvent
(
°
1c Et2O (1.1)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
-78
-78
-78
-78
3
3
3
5
5
5
50d,e 95:5
62d,e 96:4
61d,e 98:2
2
3
4
5
6
7f
8
9
Et2O (1.5)
Et2O (3)
THF (1.5)
56
96:4
87:13
96:4
94:6
95:5
92:8
75:25
t-BuOMe (1.5) CH2Cl2
-78 to 25
-78 to 25
33e
72e
i-Pr2O (1.5)
i-Pr2O (1.5)
i-Pr2O (1.5)
i-Pr2O (1.5)
AgBF4 (1.5)
CH2Cl2
CHCl3
CCl4
-60 to 25 3.5 74
-20 to 25 3.5 60
Cl(CH2)2Cl -30 to 25 3.5 47g
10
CHCl3
-60 to 25 3.5 44
a Conditions: difluorobromane 1 (1.5 equiv), Ar. b Yields after purifica-
tion by repeated decantation with hexane. c Difluorobromane 1 (1.1 equiv).
d (E)-â-Ethoxybromane 3a (7-15%) was obtained. e (E)-â-Chlorobromane
3b (3-13%) was obtained. f Difluorobromane 1 (2 equiv). g 3b (19%) was
obtained.
demanding BF3-i-Pr2O (Table 1, entry 6). The solvent dichloro-
methane transfers the chlorine atom to the electron-deficient reactive
species, such as carbocations and carbenes, via the intermediacy
of chloronium ions and ylides, respectively,8 and in our reactions,
it gives rise to the other byproduct, â-chlorodecenyl-λ3-bromane
3b. In fact, use of a less nucleophilic solvent,8a such as chloroform
or carbon tetrachloride, showed no evidences for formation of 3b,
whereas more nucleophilic 1,2-dichloroethane resulted in an
increased yield (19%) of 3b at the expense of the formation of 2a
(Table 1, entries 7-9). AgBF4 also activates difluorobromane 1 in
the reaction but affords a moderate yield of 2a with a low
stereoselectivity (Table 1, entry 10).9
Table 2 summarizes the results of regio- and stereoselective
fluoro-λ3-bromanation of terminal alkynes in chloroform in the
presence of BF3-i-Pr2O. Acetoxy, chloro, methoxycarbonyl, and
methoxy groups are compatible with our â-fluorovinyl-λ3-bromane
synthesis (Table 2, entries 6-9). Interesting methine fluorination
of the iso-butyl group afforded difluorinated vinyl-λ3-bromane 2k
(R ) Me2CFCH2) as a minor product (Table 2, entry 3). In the
reaction of sterically demanding 3,3-dimethyl-1-butyne, competition
between â-fluorination and â-methylation via 1,2-methyl shift takes
place and gave a mixture of â-fluorovinyl-λ3-bromane 2f (40%)
and (Z)-3-fluoro-2,3-dimethyl-1-butenyl-λ3-bromane (13%) (Table
2, entry 5).
Exposure of 1-decyne to difluoro-λ3-bromane 1 (1.5 equiv) and
BF3-Et2O (1.5 equiv) at -78 °C in dichloromethane under argon
afforded a 62% yield of â-fluoro-1-decenyl-λ3-bromane 2a (R )
n-C8H17) stereoselectively in an E:Z ratio of 96:4 after repeated
decantation with hexane (Table 1, entry 2). In this reaction, (E)-
â-ethoxy-3a (7%) and (E)-â-chloro-1-decenyl-λ3-bromane 3b (4%)
were obtained as byproducts. Without using BF3, no formation of
these vinyl-λ3-bromanes was observed. Hypervalent F-Br-F
bonding in 1 is efficiently polarized by the coordination of BF3,
and the positive charge on the bromine(III) is increased. In contrast
to ethoxy-λ3-bromane 3a, which gradually decomposes even during
purification by hexane decantation, fluoro-λ3-bromane 2a is stable
and no decomposition was detected when it was left standing in a
refrigerator over 1 month. The â-ethoxy group of 3a originates from
the ligand Et2O of Lewis acid BF3,7 and the formation of
â-alkoxybromanes can be controlled by using sterically more
† University of Tokushima.
‡ Universitat Duisburg-Essen
9
10460
J. AM. CHEM. SOC. 2005, 127, 10460-10461
10.1021/ja051690f CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Synthesis of â-Fluorovinyl-λ3-bromanes 2a
difluoro-
λ
3-bromane 1
yield
(%)b
ratio
E:Z
entry
R
(equiv)
2
1
2
3
4
5
6
7
8
9
n-Bu
n-C6H13
i-Bu
Me2CH(CH2)2
t-Bu
AcO(CH2)9
Cl(CH2)9
MeO2C(CH2)8
MeO(CH2)9
2.5
2
2b
2c
2d
2e
2f
2g
2h
2i
88c
75
93:7
95:5
91:9
93:7
86:14
94:6
97:3
95:5
97:3
2.5d
2
81e
82c
40f
60
2.5
2
2
2.5
2
72
62
65
2j
a Conditions: CHCl3, BF3-i-Pr2O (1.5 equiv), -60 to 25 °C (3.5 h), Ar.
b Yields after purification by repeated decantation with hexane. c Contami-
nated with a small amount of impurities. d BF3-i-Pr2O (2.5 equiv). e Vinyl-
λ3-bromane 2k (16%) was obtained. f (Z)-3-Fluoro-2,3-dimethylbutenyl-λ3-
bromane (13%) was obtained.
Figure 1. ORTEP drawing of 6. Selected bond lengths (Å) and angles
(deg): Br(1)-C(1) 1.886(5), Br(1)-C(11) 1.908(5), C(1)-C(2) 1.312(8),
Br(1)‚‚‚F(7) 2.766(3), C(1)-Br(1)-C(11) 96.8(2), C(1)-C(2)-C(3) 130.1-
(4).
Scheme 2
Scheme 4
Scheme 3
Supporting Information Available: Experimental procedures,
compound characterization data, and X-ray crystallographic data in CIF
format for 6. This material is available free of charge via the Internet
at http://pubs.acs.org.
To develop an efficient method for the synthesis of â-chlorovinyl-
λ3-bromanes, use of an external chloride anion, Bu4NCl, as an addi-
tive was examined but found to be fruitless;10 however, we found
that the internal delivery of a soft chlorine atom will make possible
the formation of â-chlorovinyl-λ3-bromanes. Thus, 5-chloro-1-
pentyne and 5-chloro-4-methyl-1-pentyne by the reaction with di-
fluorobromane 1 produced (E)-â-chloro-ω-fluorovinyl-λ3-bromanes
4a and 4b, respectively, in high yields (Scheme 2). These reactions
are exclusively stereoselective to the limits of 1H NMR (400 MHz)
detection, and no formation of Z-isomers was observed. The reaction
probably involves a 1,4-chlorine shift from sp3 to sp2 carbon atoms
as a key step11 and is termed a domino λ3-bromanation-chlorine
shift-fluorination reaction. The λ3-bromane 4 contains three kinds
of halogen atoms, F, Cl, and Br, in the molecule.
Very interestingly, in the case of 4,4-dialkyl-1-pentynes, the
domino reaction was accompanied by an additional 1,2-alkyl
rearrangement. For instance, 5-chloro-4,4-dimethyl-1-pentyne af-
forded (E)-â-chloro-δ-fluorohexenyl-λ3-bromane 5 in 78% yield
(Scheme 3). The domino λ3-bromanation-chlorine shift-alkyl
shift-fluorination reaction of 1-chloromethyl-1-propynylcyclohex-
ane resulted in the ring-enlargement of cyclohexane, yielding
fluorocycloheptane 6 in 93% yield.
References
(1) For recent reviews, see: (a) Ochiai, M. In Topics in Current Chemistry;
Wirth, T., Ed.; Springer: Berlin, 2003; Vol. 224, p 5. (b) Stang, P. J. J.
Org. Chem. 2003, 68, 2997. (c) Zhdankin, V. V.; Stang, P. J. Chem. ReV.
2002, 102, 2523. (d) Koser, G. F. In The Chemistry of Halides, Pseudo-
Halides and Azides, Supplement D2; Patai S., Rappoport, Z., Eds;
Wiley: New York, 1995; Chapter 21. (e) Varvoglis, A. The Chemistry of
Polycoordinated Iodine; VCH: New York, 1992.
(2) Okuyama, T.; Takino, T.; Sueda, T.; Ochiai, M. J. Am. Chem. Soc. 1995,
117, 3360.
(3) (a) Ochiai, M. J. Organomet. Chem. 2000, 611, 494. (b) Ochiai, M.;
Oshima, K.; Masaki, Y. J. Am. Chem. Soc. 1991, 113, 7059. (c) Okuyama,
T.; Takino, T.; Sato, K.; Ochiai, M. J. Am. Chem. Soc. 1998, 120, 2275.
(4) (a) Ochiai, M.; Takaoka, Y.; Nagao, Y. J. Am. Chem. Soc. 1988, 110,
6565. (b) Ochiai, M.; Kunishima, M.; Tani, S.; Nagao, Y. J. Am. Chem.
Soc. 1991, 113, 3135.
(5) Prakash, G. K. S.; Bruce, M. R.; Olah, G. A. J. Org. Chem. 1985, 50,
2405.
(6) Ochiai, M.; Nishi, Y.; Goto, S.; Shiro, M.; Frohn, H. J. J. Am. Chem.
Soc. 2003, 125, 15304.
(7) Ochiai, M.; Kunishima, M.; Fuji, K.; Shiro, M.; Nagao, Y. J. Chem. Soc.,
Chem. Commun. 1988, 1076.
(8) (a) White, E. H.; McGirk, R. H.; Aufdermarsh, C. A.; Tiwari, H. P.; Todd,
M. J. J. Am. Chem. Soc. 1973, 95, 8107. (b) Pirrung, M. C.; Zhang, J.;
Lackey, K.; Sternbach, D. D.; Brown, F. J. Org. Chem. 1995, 60, 2112.
(9) For fluoro-λ3-iodanation of terminal alkynes, see: (a) Hara, S.; Yoshida,
M.; Fukuhara, T.; Yoneda, N. Chem. Commun. 1998, 965. (b) Yoshida,
M.; Hara, S.; Fukuhara, T.; Yoneda, N. Tetrahedron Lett. 2000, 41, 3887.
(10) When the reaction of entry 2 in Table 1 was carried out in the presence
of Bu4NCl (1.5 equiv), a decreased yield (23%) of 2a and (E)-1,2-dichloro-
1-decene (19%) was obtained. These results probably reflect partial
oxidation of the chloride anion to Cl2 by difluorobromane 1 during the
reaction.
X-ray crystallographic analysis of fluorocycloheptane 6, shown
in Figure 1, illustrates a T-shaped structure with one fluorine atom
of the BF4 ligand at the apical site of the bromine(III) center with
a near-linear C1-Br1‚‚‚F7 triad (172.6(2)°). The root mean square
deviation of the four atoms (Br1, C1, C11, and F7) from their least-
squares planes is 0.071(2) Å.
Reaction mechanism involving the formation of tetracoordinated
λ3-bromane 7 (Scheme 4) is compatible with the formation of
unrearranged and rearranged â-haloalkenyl(aryl)-λ3-bromanes.
(11) (a) Peterson, P. E.; Duddey, J. E. J. Am. Chem. Soc. 1966, 88, 4990. (b)
Peterson, P. E. Acc. Chem. Res. 1971, 4, 407.
JA051690F
9
J. AM. CHEM. SOC. VOL. 127, NO. 30, 2005 10461