Published on the web October 8, 2011
1231
1,8-Diazabicyclo[5.4.0]undec-7-ene-promoted Regioselective Elimination
of Vicinal Dibromides Having an Adjacent O- and/or N-Functional Group
Noriki Kutsumura,* Masatoshi Iijima, Shohei Toguchi, and Takao Saito*
Department of Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601
(Received August 10, 2011; CL-110672; E-mail: nkutsu@rs.kagu.tus.ac.jp, tsaito@rs.kagu.tus.ac.jp)
We have investigated the DBU-promoted HBr-elimination of
HBr
Br
2
Br
H
1
Br
vicinal dibromides having an adjacent O- and/or N-functional
group under mild basic conditions. The elimination of 1-oxygen-
functionalized 2,3-dibromopropanes was more regioselective than
that of 1-nitrogen-functionalized 2,3-dibromopropanes. This ob-
servation suggests that the elimination selectivity is affected by the
electronegativity of the neighboring heteroatoms themselves and
not by the entire functional group.
Br
+
3
mild basic
OR
OR
R = aryl, acyl
: electron-withdrawing effect of OR
OR
condition
major
minor
: electron-withdrawing effect of bromine atoms
Scheme 1.
2-Bromo-1-alkenes are extremely useful and versatile building
blocks in organic synthesis. For example, 2-bromo-1-alkenes are
used as substrates in preparing organometallic reagents such as
vinyllithiums1 and vinyl Grignard reagents,2 coupling partners in a
variety of transition-metal-catalyzed reactions, and precursors of
¡-halo ketones3 and heterocycles.4
Table 1. Regioselective elimination of vicinal dibromides having an
oxygen functional group
Br
Br
DBU (1.1 equiv)
Br
Br
+
DMF, 60 °C
OR
OR
OR
1
2
3
Recently, Ohgiya, Nishiyama, et al. reported the regioselective
hydrogen bromide-elimination of vicinal dibromides having an
adjacent O-functional group under mild basic conditions.5 They
achieved the efficient systematic synthesis of 2-bromo-1-alkenes in
high yields without the need for expensive reagents or laboratory
equipment. According to their results and discussions, the high yield
and regioselectivity were associated with the electron-withdrawing
inductive effect of the oxygen substituent (OR), which enhances the
acidity of the hydrogen at the C2 position, along with the electron-
withdrawing inductive effects of both bromine atoms (Scheme 1).
Indeed, electron-withdrawing aryloxy- and acyloxy groups
(OR) showed the sufficient reactivity and regioselectivity.5 In our
recent work,6 a wide variety of other O-functional groups such as
benzyloxy- and silyloxy were also successfully utilized in control-
ling both the reactivity and regioselectivity of the elimination. We
therefore started to evaluate the elimination reactivity and regio-
selectivity induced by the electron-withdrawing effect of the entire
unit formed from the oxygen atom and its substituent (OR)
(Table 1). Aryloxy- and acyloxy-substituted 2,3-dibromopropanes
1a-1f gave good yields of 2a-2f, as shown in the previous reports5
(Entries 1-6). Furthermore, benzyloxy- (1g-1i), trityloxy- (TrO-,
1j), benzyloxymethyloxy- (BOMO-, 1k), and triisopropylsilyloxy-
(TIPSO-, 1l) substituted 2,3-dibromopropanes also gave excellent
yields of 2g-2l with satisfactory regioselectivities (Entries 7-12).
It should be noted that not only electron-withdrawing acyl groups
(Entries 3-6) but also the commonly used protecting groups, benzyl
(Bn), p-methoxybenzyl (PMB), trityl (Tr), benzyloxymethyl
(BOM), and triisopropylsilyl (TIPS) (Entries 7 and 9-12), could
contribute to satisfactory selectivities in organic synthesis.
2 + 3 Yield/%
[2/3]a
Entry
1
Time/h
1
2
3
4
5
6
1a: R = Ph
1b: R = p-BrC6H4
1c: R = Bz
1d: R = p-BrC6H4C(O)
1e: R = p-MeOC6H4C(O)
1f: R = Piv
1
88 [25/1]
87 [27/1]
85 [20/1]
95 [25/1]
88 [22/1]
94b [25/1]
0.5
1.3
1
0.3
0.5
7
8
9
10
11
12
1g: R = Bn
1
1
1
1
2
1
93 [11/1]
96 [12/1]
97 [13/1]
99 [10/1]
98 [15/1]
96 [15/1]
1h: R = p-ClC6H4CH2
1i: R = PMB
1j: R = Tr
1k: R = BOM
1l: R = TIPS
aRatio of 2-bromo-1-alkene 2 and 1-bromo-1-alkene 3 was determined
by 1H NMR. bYield was determined by 1H NMR using 1,4-bis(tri-
methylsilyl)benzene as internal standard.
highly stereospecific trans-elimination mechanism.7 These results
suggest that the acidity enhancement of hydrogens located at the
bases of bromine atoms are associated with the electron-with-
drawing effect of the neighboring O-functional groups (both OR1
and OR2). However, the observed regioselectivities were lower than
those required for organic synthetic applications.
We also performed the DBU-promoted elimination of vicinal
dibromides having an adjacent N-functional group (Table 3).
Intriguingly, there was no noticeable difference in regioselectivity
with substituents (R and R¤) on the nitrogen, irrespective of the
electron-withdrawing effect of R and/or R¤.
All results (Tables 1-3) suggest that the elimination selectivity
is more directly susceptible to the electronegativity of the hetero-
atoms (O and N) themselves rather than the electron-withdrawing
effects of the substituents (R) on the heteroatoms.
To confirm the hypothesis, the eliminations of the vicinal
dibromides 10 having both an O-functional group (electron-
Next, the effects of the substituent of vicinal dibromides having
both an electron-donating functional group (R1 = triisopropylsilyl-
or benzyl-) and an electron-withdrawing functional group (R2 = p-
nitrophenyl- or benzoyl-) were examined on the reaction yield and
selectivity (Table 2). Treatment of the syn-dibromides 4a and 4b and
the anti-dibromide 4c with 1.1 equivalents of DBU gave respective
mixtures of 5 and 6 with poor regioselectivity (2-1.6/1), whereas
high stereoselectivities were attained for both 5 and 6 because of the
Chem. Lett. 2011, 40, 1231-1232
© 2011 The Chemical Society of Japan
Kutsumura, Noriki
