Weakly nucleophilic conjugate bases of superacids as powerful nucleophiles in vinylic bimolecular nucleophilic substitutions of simple β- alkylvinyl(aryl)-λ3-bromanes

Article abstract of DOI:10.1021/ja200479p

We report herein, for the first time, the stereoselective synthesis of simple (E)-β-alkylvinyl(aryl)-λ³-bromanes via a boron-λ³-bromane exchange reaction and their unique bimolecular nucleophilic substitutions at the vinylic ipso carbon atom under mild conditions. Interestingly, even weakly nucleophilic anions such as conjugate bases of superacids (HBF₄, TfOH, Tf₂CH ₂, Tf₃CH, Tf₂NH, etc.) function as nucleophiles toward the vinyl-λ³-bromanes. For instance, the vinylic S_N2 reaction of (E)-vinyl-λ³-bromanes with potassium bis(triflyl)methanide stereoselectively produced (Z)-vinyloxy oxosulfonium ylides with exclusive inversion of configuration via oxygen attack, while that with potassium bis(triflyl)imide afforded predominantly (Z)-vinyloxysulfoximines. In marked contrast, (E)-β-alkylvinyl- λ³-iodanes do not undergo the vinylic S_N2 reaction with these conjugate bases of superacids. The differences between the nucleofugalities of aryl-λ³-iodanyl and aryl- λ³-bromanyl groups (the latter being greater) probably play a pivotal role in these unique reactions.

Full text of DOI:10.1021/ja200479p

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Weakly Nucleophilic Conjugate Bases of Superacids as Powerful
Nucleophiles in Vinylic Bimolecular Nucleophilic Substitutions of
Simple β-Alkylvinyl(aryl)-λ3-bromanes
Masahito Ochiai,* Takuji Okubo, and Kazunori Miyamoto
Graduate School of Pharmaceutical Sciences, University of Tokushima, 1-78 Shomachi, Tokushima 770-8505, Japan
S Supporting Information
b
such as the conjugate bases of superacids7 function as nucleophiles
toward vinyl-λ3-bromanes 3. The vastly enhanced nucleofugality of
ABSTRACT: We report herein, for the first time, the
stereoselective synthesis of simple (E)-β-alkylvinyl(aryl)-λ3-
bromanes via a boron-λ3-bromane exchange reaction and their
unique bimolecular nucleophilic substitutions at the vinylic ipso
carbon atom under mild conditions. Interestingly, even weakly
nucleophilic anions such as conjugate bases of superacids
(HBF4, TfOH, Tf2CH2, Tf3CH, Tf2NH, etc.) function as
nucleophiles toward the vinyl-λ3-bromanes. For instance, the
vinylic SN2 reaction of (E)-vinyl-λ3-bromanes with potassium
bis(triflyl)methanide stereoselectively produced (Z)-vinyloxy
oxosulfonium ylides with exclusive inversion of configuration
via oxygen attack, while that with potassium bis(triflyl)imide
afforded predominantly (Z)-vinyloxysulfoximines. In marked
contrast, (E)-β-alkylvinyl-λ3-iodanes do not undergo the vinylic
SN2 reaction with these conjugate bases of superacids. The
differences between the nucleofugalities of aryl-λ3-iodanyl and
aryl-λ3-bromanyl groups (the latter being greater) probably play
a pivotal role in these unique reactions.
aryl-λ3-bromanyl groups in comparison with aryl-λ3-iodanyl groups is
a driving force for the unique SN2V reactions.6
(E)-1-Decenyl(p-trifluoromethylphenyl)-λ3-bromane (3a)
was prepared stereoselectively via the ligand exchange reaction
of the Frohn reagent p-CF3C6H4BrF28 on Br(III) with (E)-1-
decenyldifluoroborane (2a) [2 equiv; generated in situ from potas-
sium decenylborate (1a) by the reaction with BF3 OEt2 at low tem-
3
perature in a Teflon PFA vessel under argon9] in dichloromethane
at -78 °C for 1 h (Scheme 1).10 After removal of precipitated KBF4
by rapid filtration at 0 °C, evaporation of dichloromethane in vacuo
at -30 °C followed by repeated decantation with pentane at -78 °C
afforded (E)-vinyl-λ3-bromane 3a as an amorphous solid in 85%
yield. All of the vinyl-λ3-bromanes 3a-c synthesized are thermally
labile at ambient temperature and moisture-sensitive; hence, their
yields were determined by 1H NMR spectroscopy at -40 °C with
1,1,2,2-tetrachloroethane as an internal standard. In CDCl3 solution
at 0 °C, 3a gradually decomposed to a mixture of inverted (Z)-1-
decenyl fluoride (6) and p-CF3C6H4Br with a half-life (t1/2) of 23
min, probably via SN2V reaction with BF4- anion (see Scheme S1
and Figure S1 in the Supporting Information).11 In the solid state,
however, bromane 3a can be stored at -78 °C for several weeks
without any decomposition.
imolecular nucleophilic substitution at an sp2 vinylic carbon
B
atom (SN2V reaction), in which a nucleophile attacks the σ*
orbital of the Cvinylic-LG bond from the side opposite the
leaving group (LG) to give an inverted product, has been
considered to be a high-energy process and for a long time has
been excluded as a viable pathway on both theoretical and
experimental grounds.1 A unique but unambiguous example of
intermolecular SN2V displacement 2 relies heavily on the use of a
highly powerful hypernucleofuge such as a phenyl-λ3-iodanyl
group,3 which is a better LG than superleaving triflate.4
Large vicinal coupling constants of 12.3-12.4 Hz between the
vinylic protons of λ3-bromanes 3 (CDCl3/-40 °C) indicate exclu-
sive retention of stereochemistry during the boron-λ3-bromane
exchange reaction. These coupling constants for 3 are smaller than
the value of 13.7 Hz for a λ3-iodane analogue, (E)-1-decenyl-
(phenyl)(tetrafluoroborato)-λ3-iodane (4),12 probably reflecting
the greater electron-withdrawing power of phenyl-λ3-bromanyl
groups than of phenyl-λ3-iodanyl groups.13,14 ESI-MS data for 3a
acquired in positive-ion mode in chloroform revealed prominent ion
peaks derived from monomeric, dimeric, and trimeric species at m/z
363, 813, and 1267, respectively (see Figure S2).15
Upon exposure to excess amounts of potassium triflate, a con-
jugate base of superacidic TfOH with H0 acidity of -14.1 (see
Scheme S2),16 in dichloromethane at -78 °C to room temperature,
alkenyl-λ3-bromane 3a underwent an SN2V reaction and afforded
inverted (Z)-vinyl triflate 5 stereoselectively in 54% yield along with
another SN2V product, 6 (41%) (Scheme 2). In marked contrast,
(E)-decenyl-λ3-iodane 4 did not undergo the vinylic SN2 reaction
under these conditions because of the weak nucleophilicities of
triflate and borate anions (see Scheme S3). Use of trimethylsilyl
On the other hand, in the intramolecular version, even a
common nucleofuge such as bromide can serve as a good LG:5 for
instance, 2-bromobut-2-enylamines cyclize to 2-ethyleneaziridines via
base-induced nucleophilic substitutions with stereochemical inversion
at the vinylic carbon atom. These reactions, however, cannot be
applied to the intermolecular SN2V displacement because of the
modest nucleofugality of the LG. It occurred to us that instead of
bromine, use of hypervalent λ3-bromanes as LGs with an increased
nucleofugality6 would make possible the realization of an intermole-
cular SN2V version. We report herein, for the first time, the stereo-
selective synthesis of highly active (E)-β-alkylvinyl(aryl)-λ3-bro-
manes 3 via boron-λ3-bromane exchange and their facile bimolecular
nucleophilic substitutions at the vinylic ipso carbon atom under mild
conditions. Much to our surprise, even weakly nucleophilic anions
Received: January 17, 2011
Published: February 22, 2011
r
2011 American Chemical Society
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|

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Scheme 1
Table 2. SN2V Reaction with Bis(perfluoroalkanesulfonyl)-
imide Anionsa
product (% yieldb)
entry
3
Rf
9
10
Scheme 2a
1
2
3
4
5
6
7
3a
3b
3c
3a
3b
3a
3b
CF3
CF3
CF3
9a (68)
9b (50)
9c (32)
9d (73)
9e (74)
9f (56)
9g (43)
10a (8)
10b (7c)
10c (-)d
10d (6)
10e (6)
10f (12)
10g (3)
n-C4F9
n-C4F9
(CF2CF2CF2)
(CF2CF2CF2)
a GC yields.
a Conditions: 3/potassium sulfonylimide (5 equiv)/Ar. b Isolated yields.
c 1H NMR yields. d 3,3-Dimethyl-1-butyne (18%) was produced.
Table 1. SN2V Reaction with Perfluoroalkanesulfonyl-
methanide Anionsa
singlet peak at 4.25 ppm assigned to the hydrogen atom attached to
the ylidic CdS bond in the 1H NMR spectrum (see Scheme S4).18
Potassium bis(nonaflyl)methanide also afforded (Z)-ylide 8d selec-
tively in high yield (entry 4). The presence of a sterically demanding
β-tert-butyl group in (E)-alkenyl(phenyl)-λ3-iodanes completely
inhibits the SN2 displacement with halide anions but instead results
in syn β-elimination, yielding a terminal alkyne;2 however, tert-
butylvinyl-λ3-bromane 3c did undergo the SN2V reaction with
bis(sulfonyl)methanide anions and afforded (Z)-sulfinates 8c and
8f, albeit in moderate yields. Unique but highly labile bis(triflyl)-
oxosulfonium ylide 8g was produced by the reaction of 3a with
O-nucleophilic tris(triflyl)methanide anion (entry 7).19
Potassium salts of bis(sulfonyl)imide superacids function as
ambident nucleophiles in the SN2V reaction and afforded a mixture
of O- and N-attack products (Table 2). Thus, exposure of 3a to
KNTf2 gave inverted (Z)-N-triflylsulfoximine 9a as the major product
via predominant O-attack of the imide anion, along with a small
amount of (Z)-enimide 10a (entry 1). Comparable results were ob-
tained in the reaction with nonaflyl and cyclic potassium salts (entries
4-7). A similar preference for O-phenylation over N-phenylation has
been reported in the SN1-type thermolysis and photolysis of
PhN2þNTf2-, which generates an active phenyl cation interme-
diate.20 19F NMR spectroscopy of 9a, 9b, 10a, and 10b provided the
most direct evidence for identification of these products, where the
former pair exhibit two well-resolved singlets (1:1 ratio) and the latter
a slightly more deshielded singlet (see Scheme S4).
entry
3
Rf
R0
8
yield (%)b
1
2
3
4
5
6
7
3a
3b
3c
3a
3b
3c
3a
CF3
H
H
H
H
H
H
8a
8b
8c
8d
8e
8f
81
CF3
84
43c
CF3
n-C4F9
n-C4F9
n-C4F9
CF3
93
68 (77)
31c
d
CF3SO2
8g
49 (80)
a Conditions: 3/potassium sulfonylmethanide (5 equiv)/Ar. b Isolated
1
c
yields. Numbers in parentheses are H NMR yields. 3,3-Dimethyl-1-
butyne (38% for entry 3 and 15% for entry 6) was produced. d KCTf3 (10
equiv) was used.
triflate, which can capture fluoride from weak fluoride donors with
formation of TMSF, markedly increased the selectivity for formation
of (Z)-vinyl triflate 5 (72%).
Interestingly, superstrong CH acids with two perfluoroalk-
anesulfonyl groups16 provide efficient nucleophiles for the substitu-
tion reactions of 3 (Table 1). Thus, reaction of 3a with potassium
bis(triflyl)methanide in dichloromethane at -78 °C to room
temperature stereoselectively afforded a new type of (Z)-vinyl sulfi-
nate derivative, oxosulfonium ylide 8a, in 81% yield with exclusive
inversion of configuration (entry 1). Ylide 8a was produced via
O-attack of the ambident methanide anion, and no formation of the
C-attack product was detected. This is in marked contrast to the
reported preferential C-alkylation of Tf2CHMgCl in the reaction
with allyl bromide and benzyl chloride.17 The unique structure of
Conjugate anions of these CH and NH superacids did not
undergo the vinylic SN2 reaction with vinyl-λ3-iodane 4, indicating
greater activity of vinyl-λ3-bromane 3 (see Scheme S3). Interest-
ingly, SN2V displacement of 3 with halide anions (Cl, Br, I) took
place smoothly even at -78 °C (see Table S1).
Since no method for the synthesis of (Z)-vinyloxy oxosulfonium
ylides 8 and sulfoximines 9 has been available to date, only our
unique vinylic SN2 strategy provides access to these compounds.
1
(Z)-ylide 8a was identified by H, 13C, and 19F NMR and MS
’ ASSOCIATED CONTENT
spectral analyses, especially by (1) two peaks with 1:1 intensity at
-75.6 and -80.5 ppm in the 19F NMR spectrum, indicating the
presence of different kinds of CF3 groups, and (2) a small vicinal
coupling constant of 5.6 Hz between the vinylic protons and a sharp
S
Supporting Information. Experimental details and sup-
b
porting schemes, figures, and table. This material is available free
of charge via the Internet at http://pubs.acs.org.
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’ AUTHOR INFORMATION
(19) For the synthesis of PhOS(O)(CF3)dCTf2, see:(a)Yagupolskii,
Y. L.; Pavlenko, N. V.; Yurev, I. I.; Iksanova, S. V. Zh. Org. Khim. USSR
1990, 26, 682. (b) Zhu, S.-Z.; DesMarteau, D. D. Inorg. Chem. 1993,
32, 223.
Corresponding Author
mochiai@ph.tokushima-u.ac.jp
(20) (a) Haas, A.; Yagupolskii, Y. L.; Klare, C. Mendeleev Commun.
1992, 70. (b) Laali, K. K.; Okazaki, T.; Bunge, S. D. J. Org. Chem. 2007,
72, 6758.
’ ACKNOWLEDGMENT
This work was supported by a Grant-in-Aid for Scientific
Research (B) (JSPS). We thank Central Glass Co., Ltd. (Japan)
for a generous gift of BrF3.
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