Synthesis of bromoallenyl pyrrolidines via 1,4-addition to 1,3-enynes

Article abstract of DOI:10.1007/s11426-010-4133-6

The discovery of the novel reactivity of conjugated enynes, mediated by readily available halogenation reagents, opens a broad range of mechanistically unique pathways for the synthesis of highly functionalized chiral allene derivatives. Bromoallenyl pyrr

Full text of DOI:10.1007/s11426-010-4133-6

SCIENCE CHINA
Chemistry
January 2011 Vol.54 No.1: 56–60
doi: 10.1007/s11426-010-4133-6
• ARTICLES •
· SPECIAL TOPIC · The Frontiers of Chemical Biology and Synthesis
Synthesis of bromoallenyl pyrrolidines via 1,4-addition
to 1,3-enynes
WERNESS Jenny B.2 & TANG WeiPing1*
1School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA
2Department of Chemistry, University of Wisconsin, Madison, WI 53705, USA
Received August 9, 2010; accepted August 22, 2010
The discovery of the novel reactivity of conjugated enynes, mediated by readily available halogenation reagents, opens a broad
range of mechanistically unique pathways for the synthesis of highly functionalized chiral allene derivatives. Bromoallenyl
pyrrolidines can be synthesized via 1,4-addition of sulfonamide nitrogen nucleophiles and halogens to conjugated enynes. This
process can lead to simultaneous formation of a highly functionalized axially chiral allene and a stereogenic center under eco-
nomical and environmentally friendly reaction conditions.
halocyclization, halogenation, conjugated enynes, allene, bromoallene, pyrrolidine
formed for intramolecular addition of nucleophiles and
electrophiles to conjugated 1,3-enynes (Scheme 1).
1 Introduction
We have previously developed a BuLi-catalyzed intra-
molecular 1,4-hydroamination of conjugated enynes to gen-
erate allenyl pyrrolidines 3 and 4 (Nu = NR, X = H) [6].
This method has been successfully applied to the synthesis of
natural products irniine and irnidine [6]. Although this is a
useful reaction for the production of functionalized nitrogen
Addition reactions to alkenes and alkynes are powerful
methods for the introduction of functionality to organic
compounds and have become one of the most influential
fields in modern synthetic organic chemistry. While the
regio- and stereoselectivity of the addition to alkenes or
alkynes have been studied extensively for the formation of
adjacent stereogenic centers or geometrically defined alkenes,
little is known about the 1,4-addition across conjugated
enynes, in which a chiral allene can be co-introduced with a
stereogenic center. Allenes are important structural motifs
frequently present in natural products [1] and key intermedi-
ates in the synthesis of structurally complex targets [2–5].
Although numerous methods have been developed for the
creation of center chirality, only a limited number of such
methods are known for axially chiral allenes [2–5].
We envision that conjugated 1,3-enyne may represent a
new platform for the discovery of novel stereoselective ad-
dition reactions. Both 1,2- and 1,4-addition products may be
Scheme 1 Regio- and diastereoselectivity in the intramolecular addition
to 1,3-enynes.
*Corresponding author (email: wtang@pharmacy.wisc.edu)
© Science China Press and Springer-Verlag Berlin Heidelberg 2011
chem.scichina.com www.springerlink.com

Werness JB, et al. Sci China Chem January (2011) Vol.54 No.1
57
heterocycles, we were not able to control the diastereoselec-
tivity under the reaction conditions. The scope and limita-
tions of this hydroamination have been disclosed recently [7].
Halogen-promoted intramolecular additions of oxygen, ni-
trogen, and carbon nucleophiles to olefins have been widely
used for the synthesis of cyclic compounds [8, 9]. Although
it is well-known that nucleophiles will attack the halonium
ion from the opposite face of the olefin to generate anti-
addition product 2 (X = halogen), the diastereoselectivity
for the 1,4-addition to 1,3-enynes has rarely been studied.
The first intramolecular 1,4-addition of alcohol and bro-
mine (1,4-bromoetherification) to conjugated enynes was
reported in 1982 by Feldman et al. in the biomimetic syn-
thesis of racemic panacene [10–12]. A 1:1 diastereomeric
ratio (dr) was observed for the newly generated stereogenic
center and axially chiral allene. The 1,4-bromoetherification
strategy was also applied to the synthesis of laurallene [13],
(−)-kumausallene [14, 15], and a simple model system [16].
Generally, no or low diastereoselectivity were observed.
Recently, Canesi et al. reported that high diastereoselectivi-
ty (dr > 20:1) could be obtained for 1,4-bromoetherification
of conjugated trans-enynes in non-polar solvents [17]. How-
ever, the major diastereomer is the undesired epimer of nat-
umn chromatography was carried out on silica gel 60 (Sil-
licycle, 40-63 μm). All reactions were carried out under an
argon atmosphere. Chemical reagents and solvents were
purchased from Aldrich, Acros, and Alfa Aesar.
2.2 Synthesis of sulfonamides 7 and 9
General procedure (Scheme 2): A solution of primary amine
5 or 8 (0.440 mmol) in CH2Cl2 (4.4 mL) was cooled to
−78 °C. To the above solution was added Et3N (0.08 mL,
0.572 mmol) followed by arylsulfonylchloride (0.528
mmol). The above solution was then stirred for 1 h, warmed
to rt, stirred for overnight before quenching with water. The
aqueous solution was extracted with CH2Cl2. The organic
layers were combined, dried over Na2SO4 and concentrated
in vacuo. Flash column chromatography (20% EtOAc in
hexanes with 1% Et3N) provided sulfonamide 7 or 9 in
70%–87% yields.
7a 1H NMR (500 MHz, CDCl3, TMS): δ1.23(s, 9H), 1.55
(quintet, J = 7.2 Hz, 2H), 2.06 (dq, J = 1.6, 7.2 Hz, 2H), 2.49
(s, 3H), 3.22 (q, J = 7.2 Hz, 2H), 5.40 (dq, J = 1.6, 15.6, 1H),
5.89 (dt, J = 6.8, 15.6 Hz, 1H), 7.73−7.75 (m, 2H), 7.91–7.94
(m,2H).13C NMR (100 MHz, CDCl3): δ21.7,28.0,29.0,30.0,
31.2,42.8, 76.9, 97.9,111.4,127.3,130.0,137.2,141.0, 143.7.
IR: ν 3281, 2970, 1738, 1599, 1452, 1362, 1154, 1087 cm–1.
HRMS (ESI) for C18H25NO2S (M+H), 320.167876 (calcd),
found 320.16789
ural product panacene. The diastereoselective 1,4-
addi-
tion of various nucleophiles and halogen electrophiles to
conjugated enynes as a general method for the preparation
of functionalized allenes has not been developed.
We recently reported the first 1,4-addition of a carbox-
ylic acid and bromine (1,4-bromolactonization) to 1,3-
enynes for the preparation of bromoallenyl lactone 4 (X =
Br, Nu = carboxylic acid) [18]. In the absence of any cata-
lyst, the NBS exhibited no reactivity and no lactone was
observed after 1 h. The addition of nucleophilic or basic
amine catalysts results in rapid formation of bromoallenyl
lactone. We did not observe any 1,2-addition product. Al-
most all catalysts provided syn-addition product 4 as the
major isomer. Over 20:1 dr was observed with 2 mol%
DABCO (1,4-diazobicyclic[2,2,2]octane). A chiral bifunc-
tional catalyst was also developed to afford chiral bromo-
allenyl lactone in high enantioselectivity and diastereoselec-
tivity from 1,3-(Z)-enynes [19]. We described here our
study on the 1,4-addition of different sulfonamide nitrogen
nucleophiles and bromine electrophiles to 1,3-enynes for the
synthesis of bromoallenyl pyrrolidines. In all cases,
1,4-addition occurred selectively. High diastereoselectivity
was observed for certain sulfonamide nitrogen nucleophiles.
1
7b H NMR (400 MHz, CDCl3): δ 8.68 (d, J = 2.0 Hz,
1H), 8.56 (dd, J = 8.4, 2.0 Hz, 1H), 8.34 (d, J = 8.4 Hz, 1H),
5.91 (dt, J = 15.6, 7.6 Hz, 1H), 5.45 (d, J = 15.6, 1H), 2.89
(s, 2H), 2.02 (dd, J = 6.4, 2H), 1.23 (s, 9H), 0.93 (s, 6H).
13C NMR (125 Hz, CDCl3): δ 25.1, 28.1, 31.2, 35.1, 42.3,
53.6, 77.3, 98.2, 113.9, 121.0, 127.3, 132.9, 137.3, 139.4,
148.2, 150.0. IR: ν 3278, 2969, 1738, 1599, 1454, 1362,
1326, 1159, 1094 cm−1. HRMS (ESI) for C19H25N3O6S
(M+H), 424.1537 (calcd), found 424.1535.
9a 1H NMR (400 MHz, CDCl3, TMS): δ 0.98(s,6H), 1.70
(s, 2H), 2.43 (s, 3H), 2.68 (d, J = 7.2 Hz, 2H), 2.80 (d, J = 2.0
Hz, 1H), 5.30 (s, 1H), 5.42 (dq, J = 1.2, 15.6, 1H), 6.12 (dt, J
= 7.6, 15.6 Hz, 1H), 7.31 (d, J = 8.8 Hz, 2H), 7.73 (d, J = 8.8
2 Experimental
2.1 General experimental
1H NMR spectra were recorded on either a Varian 400 or
500 MHz spectrometer. The chemical shifts are reported
relative to TMS. Analytical thin-layer chromatography
(TLC) was performed on silica 60F-254 plates. Flash col-
Scheme 2 Preparation of enynes tethered with sulfonamides.

58
Werness JB, et al. Sci China Chem January (2011) Vol.54 No.1
Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 21.7, 25.0, 34.9,
43.0, 53.0,76.3,82.4,111.8,127.3,130.0,137.1,142.3,143.6.
IR: ν 3304, 2965, 1611, 1566, 1421, 1332, 1302, 1154, 1087
cm−1. HRMS (ESI) for C16H21NO2S (M+H), 292.1366
(calcd), found 292.1362.
7.31 (d, J = 8.5 Hz, 2H), 7.73 (d, J = 8.5 Hz, 2H). 13C NMR
(100 Hz, CDCl3): δ 24.5, 28.9, 29.2, 31.7, 37.4, 48.7, 58.2,
100.9, 109.1, 127.7, 129.9, 135.0, 143.6, 196.2. IR: ν 3195,
2948, 1738, 1732, 1455, 1349, 1216, 1161, 1093 cm−1.
HRMS (ESI) for C18H24BrNO2S (M+H), 398.078389
(calcd), found 398.07783.
9b 1H NMR (500 MHz, CDCl3, TMS): δ0.94(s,6H),2.09
(d, J = 8.0 Hz, 2H), 2.80 (s, 1H), 2.88 (d, J = 6.5 Hz, 2H), 5.39
(t, J = 6.5 Hz, 1H), 5.47 (d, J = 16 Hz, 1H), 6.14 (dt, J = 7.5,
16 Hz, 1H), 8.35 (d, J = 8.0 Hz, 1H), 8.58 (d, J = 8.0 Hz, 1H),
8.67 (s, 1H). 13C NMR (100 Hz, CDCl3): δ 25.0, 35.1, 43.0,
53.5, 76.8, 82.1, 112.3, 121.0, 127.4, 132.9, 139.1, 141.4,
141.5, 150.1. IR: ν 3349, 3101, 2662, 1543, 1418, 1382,
1361, 1186, 1169, 1064 cm−1. HRMS (ESI) for
C15H17N3O6S (M+H), 368.0911 (calcd), found 368.0909.
1
10a Minor diastereomer: H NMR (500 MHz, CDCl3): δ
1.19 (s, 9H), 1.6−1.9 (m, 4H), 2.43 (s, 3H), 3.1−3.2 (m, 1H),
3.5−3.6 (m, 1H), 4.32−4.36 (m, 1H), 5.44 (d, J = 5.0 Hz,
1H), 7.31 (d, J = 8.5 Hz, 2H), 7.72 (d, J = 8.5 Hz, 2H). 13C
NMR (100 Hz, CDCl3): δ 24.1, 29.3, 29.7, 31.1, 37.4, 48.7,
58.2, 100.7, 108.5, 127.6, 129.9, 135.2, 143.7, 196.8.
1
10b Major diastereomer: H NMR (500 MHz, CDCl3): δ
1.08 (s, 3H), 1.13 (s, 9H), 1.15 (s, 3H), 1.69 (dd, J = 13.0,
9.0 Hz, 1H), 2.02 (ddd, J = 12.5, 7.0, 1.5 Hz, 1H), 3.26 (d, J
= 10.5 Hz, 1H), 3.63 (dd, J = 10.5, 1.5 Hz, 1H), 4.57 (ddd, J
= 8.5, 7.5, 7.5 Hz, 1H), 4.96 (d, J = 8.0 Hz, 1H), 8.46−8.55
(m, 3H). 13C NMR (125 Hz, CDCl3): δ 25.6, 29.7, 37.0,
38.2, 59.5, 62.0, 98.7, 107.7, 119.7, 126.8, 133.9, 139.6,
147.9, 149.7, 178.1, 197.3. IR: ν 3105, 2968, 1555, 1539,
1460, 1363, 1162, 1107, 1064 cm−1. HRMS (ESI) for
C19H24BrN3O6S (M+H), 502.0642 (calcd), found 502.0645.
10b Minor diastereomer: 1H NMR (500 MHz, CDCl3): δ
1.02 (s, 3H), 1.15 (s, 9H), 1.16 (s, 3H), 1.77 (dd, J = 12.5,
8.0 Hz, 1H), 2.03 (ddd, J = 12.5, 7.5, 1.5 Hz, 1H), 3.22 (d, J
= 10.5 Hz, 1H), 3.48 (dd, J = 10.5, 1.5 Hz, 1H), 4.69 (ddd, J
= 8.0, 7.5, 6.5 Hz, 1H), 5.32 (d, J = 6.5 Hz, 1H), 8.24 (d, J =
8.0 Hz, 1H), 8.42–8.50 (m, 2H).
1
9c H NMR (400 MHz, CDCl3, TMS): δ 0.89 (s, 6H),
2.04 (d, J = 8.4 Hz, 2H), 2.75 (d, J = 6.4 Hz, 2H), 2.81
(d, J = 2.0 Hz, 1H), 5.13 (t, J = 6.8 Hz, 1H), 5.43 (dd, J =
1.2, 15.6 Hz, 1H), 6.11 (dt, J = 8.0, 15.6 Hz, 1H), 8.06 (d,
J = 8.8 Hz, 2H), 8.38 (d, J = 8.8 Hz, 2H). 13C NMR (100
MHz, CDCl3): δ 25.0, 35.0, 42.9, 53.0, 76.8, 82.1, 112.2,
124.8, 128.5, 141.8, 145.9, 150.3. IR: ν 3300, 2960, 1607,
1530, 1424, 1349, 1311, 1164, 1092 cm−1. HRMS (ESI)
for C15H18N2O4S (M+H), 323.106004 (calcd), found
323.105800.
2.3 Synthesis of bromoallenyl pyrrolidines 10 and 11
General procedure (Scheme 3): To a solution of sulfona-
mide 7 or 9 in CHCl3 or CDCl3 (0.1 M) was added DABCO
(10 mol%) and NBS (1.2 equiv). The reaction was stirred at
room temperature until the starting material was consumed
(10 min to 72 h). The solvent was evaporated and the resi-
due was purified by column chromatography on silica gel to
afford bromoallenyl pyrrolidines 10 and 11 in 70%−88%
yield.
11a Major diasteromer: 1H NMR (500 MHz, CDCl3): δ
1.08 (s, 6H), 1.55 (s, 1H), 1.70−1.81 (m, 2H), 2.44 (s, 3H),
3.07 (d, J = 10.0 Hz, 1H), 3.21 (d, J = 10.0 Hz, 1H), 4.16
(dddd, J = 9.5, 8.5, 7.0, 2.0 Hz, 1H), 5.70 (dd, J = 6.0, 6.0
Hz, 1H), 6.01 (dd, J = 5.5, 1.5 Hz, 1H), 7.33 (d, J = 8.0 Hz,
2H), 7.74 (d, J = 8.0 Hz, 2H). 13C NMR (125 Hz, CDCl3): δ
21.8, 26.8, 37.9, 46.3, 57.7, 61.6, 74.4, 103.5, 127.9, 130.0,
134.8, 143.9, 201.5. IR: ν 3119, 2972, 2362, 1739, 1366,
1217, 1138, 1075 cm−1. HRMS (ESI) for C16H20BrNO2S
(M+H), 370.047089 (calcd), found 370.04677
1
10a Major diastereomer: H NMR (500 MHz, CDCl3): δ
1.21 (s, 9H), 1.6−1.9 (m, 4H), 2.43 (s, 3H), 3.1−3.2 (m, 1H),
3.4–3.5 (m, 1H), 4.25−4.27 (m, 1H), 5.41 (d, J = 5.0 Hz, 1H),
11a Minor diasteromer: 1H NMR (500 MHz, CDCl3): δ
1.10 (s, 6H), 1.55 (s, 1H), 1.70-1.81 (m, 2H), 2.44 (s, 3H),
3.02 (d, J = 10.0 Hz, 1H), 3.20 (d, J = 10.0 Hz, 1H), 4.21
(ddd, J = 9.5, 8.5, 7.0, 2.0 Hz, 1H), 5.68 (dd, J = 6.0, 6.0 Hz,
1H), 6.12 (dd, J = 5.5, 1.5 Hz, 1H), 7.32 (d, J = 8.0 Hz, 2H),
7.71 (d, J = 8.0 Hz, 2H). 13C NMR (125 Hz, CDCl3): δ 21.8,
26.8, 37.9, 46.2, 57.5, 61.5, 74.4, 103.8, 127.8, 129.9, 134.7,
143.8, 201.3.
11b Major diastereomer: 1H NMR (500 MHz, CDCl3): δ
0.82 (s, 3H), 1.11 (s, 3H), 1.72 (dd, J = 13.0, 7.5 Hz, 1H),
1.87 (dd, J =13.0, 7.5 Hz, 1H), 3.12 (d, J = 9.5 Hz, 1H),
3.21 (d, J = 9.5 Hz, 1H), 4.27 (dddd, J = 7.5, 7.5, 6.5, 1.5
Hz, 1H), 5.51 (dd, J = 6.5, 5.5 Hz, 1H), 6.03 (dd, J = 5.5,
1.5 Hz, 1H), 8.42 (d, J = 9.0 Hz, 1H), 8.38−8.40 (m, 2H).
13C NMR (100 Hz, CDCl3): δ 26.1, 37.8, 46.5, 58.5, 61.9,
74.5, 103.1, 120.7, 127.3, 133.5, 143.0, 148.1, 150.1, 201.6.
IR: ν 3070, 2962, 1960, 1606, 1530, 1468, 1350, 1313, 1194,
Scheme 3 Synthesis of bromoallenyl pyrrolidines via 1,4-addition of
sulfonamides and bromine to 1,3-enynes.

Werness JB, et al. Sci China Chem January (2011) Vol.54 No.1
59
1164, 1092, 1012 cm−1. HRMS (ESI) for C15H16BrN3O6S
(M+H), 446.0016 (calcd), found 446.0015.
Although we have not been able to identify the relative
stereochemistry of the major and minor diastereomer for
bromoallenyl pyrrolidines 10 and 11, we assumed syn-
addition also occurred for sulfonamide nitrogen nucleo-
philes based on our observation for carboxylic acid nucleo-
phile and reports from literature for alcohol nucleophiles as
discussed in the introduction. Steric interaction between
NBS and sulfonamide nucleophile would be much more
significant than steric interaction between NBS and carbox-
ylic acid nucleophile during the syn-addition. This may be
the reason for the general low selectivity observed for sul-
fonamide nitrogen nucleophiles in these addition reactions.
The two nitro groups on substrate 9b not only increased the
acidity of the sulfonamide NH but also increased the steric
interactions between the sulfonamide and the incoming
NBS during the syn-addition. Removing the nitro group on
the ortho-position may minimize this potential steric inter-
action. Indeed, a 10:1 dr and 88% of isolated yield was ob-
tained for substrate 9c, which only has a para-nitro electron
withdrawing group on the benzene ring.
11b Minor diastereomer: 1H NMR (500 MHz, CDCl3): δ
0.79 (s, 3H), 1.12 (s, 3H), 1.75 (dd, J = 13.0, 7.5 Hz, 1H),
1.87 (dd, J =13.0, 7.5 Hz, 1H), 3.12 (d, J = 9.5 Hz, 1H),
3.21 (d, J = 9.5 Hz, 1H), 4.32 (dddd, J = 7.5, 7.5, 6.5, 1.5
Hz, 1H), 5.60 (dd, J = 6.5, 5.5 Hz, 1H), 6.16 (dd, J = 5.5, 1.5
Hz, 1H), 8.02 (d, J = 9.0 Hz, 1H), 8.38–8.40 (m, 2H).
11c Major diastereomer: 1H NMR (500 MHz, CDCl3): δ
0.82 (s, 3H), 1.11 (s, 3H), 1.74 (d, J = 7.5 Hz, 1H), 1.87 (d,
J = 8.0 Hz, 1H), 3.22 (s, 2H), 4.26 (dddd, J = 7.5, 7.5, 6.5,
1.0 Hz, 1H), 5.51 (dd, J = 6.5, 5.5 Hz, 1H), 6.03 (dd, J = 5.5,
1.0 Hz, 1H), 8.06 (d, J = 8.5 Hz, 2H), 8.39 (d, J = 8.5 Hz,
2H). 13C NMR (100 Hz, CDCl3): δ 26.4, 38.2, 46.7, 58.1,
61.5, 74.8, 102.6, 124.6, 128.9, 144.4, 150.3, 201.8. IR: ν
3072, 2965, 2876, 1962, 1607, 1532, 1352, 1315, 1196,
1167, 1094, 1031 cm–1. HRMS (ESI) for C15H17BrN2O4S
(M+H), 401.016517 (calcd), found 401.01616.
1
11c Minor diastereomer: H NMR (500 MHz, CDCl3): δ
0.81 (s, 3H), 1.12 (s, 3H), 1.71 (d, J = 7.5 Hz, 1H), 1.89 (d,
J = 8.0 Hz, 1H), 3.21 (s, 2H), 4.32 (ddd, J = 7.5, 7.5, 6.5,
1H), 5.61 (dd, J = 6.5, 5.5 Hz, 1H), 6.15 (dd, J = 5.5, 1.0 Hz,
1H), 8.02 (d, J = 8.5 Hz, 2H), 8.38 (d, J = 8.5 Hz, 2H).
3 Results and discussion
We also tried substrates with substituents other than
tert-butyl group or hydrogen on the terminal position of the
alkyne, such as sulfonamides 12a and 12b. Surprisingly, no
reaction occurred for substrate 12a in the absence or the
presence of DABCO catalyst after 12 h. About 25% con-
version was observed for substrate 12b after 12 h and longer
reaction time did not improve the conversion much. Further
study of the scope and the enantioselective process of this
reaction is currently under investigation in our lab.
The sulfonamide substrates 7 and 9 were prepared via sul-
fonylation of primary amines 5 and 8 (Scheme 2), which are
prepared according to our previously published procedures
[6, 7]. In the absence of any catalyst, sulfonamide 7a un-
derwent 1,4-addition selectively mediated by NBS in chlo-
roform to yield bromoallenyl pyrrolidine 10a in 55% yield
after 2 h. However, the dr for the two 1,4-addition products
(syn- or anti-addition) is only about 1:1. In the presence of
catalytic amount of DABCO (10 mol%), the dr was im-
proved to 6:1 and the yield was improved to 77% (Scheme
3). Changing solvents and catalysts did not improve the dr
further.
4 Conclusions
Since high diastereoselectivity was observed for carbox-
ylic acid nucleophiles [18], we envision that more acidic
nitrogen nucleophile may provide higher diastereoselectivi-
ty. Next we decided to change the pKa of the sulfonamide
NH by attaching two electron withdrawing nitro groups.
However, the dr for product 7b dropped to about 4:1. It also
took much longer time (72 h) for the complete consumption
of starting material. Product 7b was isolated in 70% yield.
To minimize the steric interaction of the substituent on
the terminal position of the alkyne with incoming electro-
philes, we then prepared sulfonamide 9a−9c with a hydro-
gen on the terminal position of the alkyne instead of a bulky
tert-butyl group. In the presence of DABCO catalyst, sub-
strate 9a provided a 5:1 dr. Substrate 9b with two electron
withdrawing nitro groups gave a dr of 6:1. The reaction
went to completion in about 10–20 min for both substrates.
In summary, we have a developed a diastereoselective syn-
thesis of bromoallenyl pyrrolidines via 1,4-addition of sul-
fonamide nucleophiles and bromine electrophiles across
conjugated 1,3-enynes. The intrinsic regioselectivity for
these reactions is 1,4-addition. The diastereoselectivity was
improved to up to 10:1 after careful tuning of the electronic
and steric properties of the sulfonamide nucleophiles. Addi-
tion of other nucleophiles and halogen electrophiles across
conjugated 1,3-enynes are currently under our investigation
for the synthesis of broad ranges of bromoallenes.
We thank the University of Wisconsin-Madison and the American Chemi-
cal Society Petroleum Research Fund (48092-G) for funding.
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