Reactions of carbon nucleophiles with 2,2,3-trisubstituted ethynylaziridines

Article abstract of DOI:10.1016/j.tetasy.2013.08.009

Carbon nucleophiles were used to open a 2,2,3-trisubstituted ethynylaziridine. A cyanide nucleophile opened the ring at the more substituted carbon, proceeding regioselectively with inversion of configuration. In an attempt to expand upon the scope of the reaction, Normant cuprates were reacted with a 2,2,3-trisubstituted ethynylaziridine. This reaction produced chiral allenes via an anti-S_N2′ pathway. X-ray analysis of a derivative allowed the absolute stereochemistry of the anti-allenes to be assigned as P.

Full text of DOI:10.1016/j.tetasy.2013.08.009

Tetrahedron: Asymmetry 24 (2013) 1233–1239
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Reactions of carbon nucleophiles with 2,2,3-trisubstituted
ethynylaziridines
⇑
Brandon T. Kelley, Madeleine M. Joullié
Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 July 2013
Accepted 14 August 2013
Carbon nucleophiles were used to open a 2,2,3-trisubstituted ethynylaziridine. A cyanide nucleophile
opened the ring at the more substituted carbon, proceeding regioselectively with inversion of configura-
tion. In an attempt to expand upon the scope of the reaction, Normant cuprates were reacted with a 2,2,3-
trisubstituted ethynylaziridine. This reaction produced chiral allenes via an anti-SN20 pathway. X-ray
analysis of a derivative allowed the absolute stereochemistry of the anti-allenes to be assigned as P.
Published by Elsevier Ltd.
R1
Nuc
R3
NHR2
1. Introduction
R1
NHR2
R3
+
In connection with a research program focused on 2,2,3-trisub-
stituted ethynylaziridines, we have investigated their reactions
with carbon nucleophiles and compared them to the reactions of
2,2,3-alkyl aziridines. Differently substituted aziridines are
reported to give different regio- and stereochemical products.
Ethynylaziridines are unique in that they may undergo ring open-
ing in three different ways: attack at the propargylic position
(SN2P), attack at the homopropargylic position (SN2H), or attack
on the alkyne (SN20) producing an allene (Fig. 1).1 Axially chiral
allenes are a diverse and synthetically useful class of compounds.2
Although there are many effective methods for synthesizing
non-racemic chiral allenes, the strategy chosen depends on many
factors.1a–e,3 The synthesis of axially chiral allenes by SN20 addition
of ethynylaziridines was of interest to us.
R1
Nuc
SN2P
R3
SN2H
nucleophile
Nuc
NR2
NHR2
R3
R1
•
SN2'
Figure 1. Nucleophilic addition of an alkynyl aziridine.
intramolecular amination of chiral bromoallenes.7 The cis- and
trans-alkynyl aziridines were also obtained from protected
(S)-a-amino acids under Mitsunobu conditions, after separation
of the two diastereomeric alkynyl amino alcohols.1e The addition
of racemic allenylzinc to enantiopure N-tert-butanesulfinimines
provided enantiopure cis-ethynylaziridines.8 Aziridine aldehyde
dimers participated in a Wittig-type transformation that afforded
a dibromo olefin. A one step homologation with the Bestmann–
Ohira reagent in methanol and potassium carbonate afforded
2-ethynylaziridines with different substitution patterns.9
2-Ethynylaziridines are well-known reagents; however, they
are still challenging to synthesize stereoselectively, and have been
prepared by different methods. N-Sulfonyl imines and sulfonium
ylids afforded cis-2-ethynylaziridines in good yields.4 Propargylic
aziridines were prepared by the lithiation of cinnamyl chloride
and reaction with a
-chloroimines.5 The metallation of 3-trimethyl-
silyl-1-chloroprop-2-yne and reaction with N-benzylimines affor-
ded stereospecifically trans-propargylic aziridines in good yields.
The Mitsunobu reaction of amino alcohols bearing an ethynyl
group was also successfully employed to prepare 2-ethynylaziri-
dines with high enantiomeric purities (91–98% ee).6 The base-
mediated intramolecular amination of bromoallenes with an axial
chirality afforded a cis-selective synthesis of 2-ethynylaziridines. A
cis-selective synthesis of 2-ethynylaziridines was accomplished by
We have synthesized chiral 2,2,3-trisubstituted ethynylaziri-
dines that exhibit unusual reactivity in nucleophilic ring opening
reactions.10 Although chiral substituted aziridines have been used
to make chiral amino allenes by organocopper-mediated reac-
tions,1b none of these aziridines had the unique 2,2,3-substitution
of the compounds we prepared. Therefore, because of the unprec-
edented substitution of the aziridines we synthesized, we exam-
ined the reactions of four differently 2,2,3-trisubstituted
aziridines with carbon nucleophiles. We chose aziridines that can
be synthesized stereoselectively and in fewer synthetic steps. We
also chose both ethynyl and ethyl substituents to compare the ef-
fect of the two groups and the nitrogen protecting group was
⇑
Corresponding author. Tel.: +1 215 898 3158.
E-mail addresses: bkelley@sas.upenn.edu (B.T. Kelley), mjoullie@sas.upenn.edu
(M.M. Joullié).
0957-4166/$ - see front matter Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tetasy.2013.08.009

1234
B. T. Kelley, M. M. Joullié / Tetrahedron: Asymmetry 24 (2013) 1233–1239
OTBS
OTBS
OTBS
OTBS
N
N
N
N
Ts
Ts
Ns
Ns
1
3
4
2
Figure 2. Aziridines investigated.
varied for compatibility with the reaction conditions. The aziri-
dines chosen 1–4 are shown in Figure 2.
The ethyl aziridines lack the alkynyl functionality, but the reac-
tions of aziridines 2 and 4 were of interest based on the previous
trisubstituted aziridine ring opening reactions.10c If aziridines 2
and 4 could undergo ring opening at the more substituted carbon
with carbon nucleophiles, a diverse array of quaternary carbons
could be synthesized in a stereospecific manner. With this in mind,
we began with simple carbon nucleophiles such as cyanide. While
the cyanide was successful we decided to investigate organometal-
lic reagents, such as organocopper-mediated reagents, in order to
build diversity.
We first attempted the reactions using aziridines 2 and 4. In
order to achieve this goal, an organocuprate was used as the nucle-
ophile due to its weak basicity. A Gilman type cuprate was used
but the desired ring opened product was not observed. Aziridine
2 decomposed under the reaction conditions, a problem which
could be due to the incompatibility of the 2-nitrosulfonyl
protecting group. Aziridine 4 yielded recovered starting material
indicating that no reaction had occurred (Scheme 4).
2. Results and discussion
Aziridines 1–4 were prepared from the same starting material,
D
-serine (Scheme 1). Using conditions previously developed in
our laboratory,10b,c the hydrochloride salt of
D
-serine was protected
as its tert-butyl carbamate and coupled with the Weinreb amine
hydrochloride salt, followed by N,O-acetal formation and treat-
ment with methyllithium to afford oxazolidine 5. Nucleophilic
addition to the keto group of 5 gave two diastereomers 6 and 7 that
were separable by recrystallization. Diastereomer 6 served as a
branching point for the different aziridines. Aziridines 1 and 3 were
synthesized by removing the acid labile group and protecting the
amine with 2-nitro and 4-toluenesulfonyl chlorides to provide
the sulfonamides 8 and 10, respectively. Protection of the primary
alcohol with tert-butyldimethylsilyl chloride (TBSCl) gave the silyl
ethers 9 and 11. Ring closure using Mitsunobu conditions provided
the known aziridine 1 and the new aziridine 3 (Scheme 1).
Next we turned our attention to the ethynyl aziridines. With the
decomposition of the 2-nitrosulfonyl protecting group in the
Ethyl aziridines 2 and 4 were synthesized in a similar manner to
the ethynyl aziridines. Starting from tertiary alcohol 6, the ethynyl
group was reduced under hydrogenolysis conditions to give the ter-
tiary alcohol 12. Removal of the acid sensitive groups and protecting
the amines as the 2-nitro and 4-toluenesulfonamides afforded com-
pounds 13 and 15, respectively. Protection of the primary alcohols
with TBSCl gave the silyl ethers 14 and 16. Ring closure under Mits-
unobu conditions provided aziridines 2 and 4 (Scheme 2).
KCN
18-crown-6
OTBS
C
OTBS
N
N
MeCN, rt, 65%
Ns
NHNs
17
1
Scheme 3. Ring opening of ethynyl aziridine 1 with potassium cyanide.
O
O
1) NaHCO3, (Boc)2O, 89%
+
2) EDCI, HNMe(OMe)•HCl, 84%
MgBr
THF, 76%
11:1
HO
HO
HO
HO
OH
NH2•HCl
O
O
O
BocN
5
BocN
6
3) 2,2-DMP, BF3•OEt2
BocN
4) MeLi, 64% over 2 steps
D-serine
7
i, conc. HCl/THF
OTBS
OTBS
ii. NsCl, Na2CO3,
rt, THF/H2O
HO
HO
OH
OH
HO
HO
OTBS
OTBS
DIAD, PPh3
THF, rt, 69%
TBSCl, NEt3, DMAP
CH2Cl2, rt, quant
N
O
Ns
BocN
6
NHNs
8
NHNs
80% over 2 steps
1
9
i, conc. HCl/THF
ii. TsCl, Na2CO3,
rt, THF/H2O
TBSCl, NEt3, DMAP
CH2Cl2, rt, quant
DIAD, PPh3
THF, rt, 84%
N
Ts
NHTs
10
NHTs
81% over 2 steps
3
11
Scheme 1. Synthesis of ethynyl aziridines 1 and 3.
i, conc. HCl/THF
OTBS
ii. NsCl, Na2CO3,
rt, THF/H2O
HO
HO
OH
OH
HO
HO
OTBS
OTBS
DIAD, PPh3
TBSCl, NEt3, DMAP
CH2Cl2, rt, 94%
H2, Pd/C
N
HO
HO
Ns
O
O
NHNs
NHNs
THF, rt, 76%
EtOH, 89%
BocN
12
61% over 2 steps
BocN
6
13
2
14
i, conc. HCl/THF
ii. TsCl, Na2CO3,
rt, THF/H2O
OTBS
DIAD, PPh3
TBSCl, NEt3, DMAP
CH2Cl2, rt, 62%
N
Ts
NHTs
15
81% over 2 steps
NHTs
16
THF, 50 °C, 55%
4
Scheme 2. Synthesis of ethyl aziridines 2 and 4.

B. T. Kelley, M. M. Joullié / Tetrahedron: Asymmetry 24 (2013) 1233–1239
1235
n-BuLi
Me2SCuBr
an activating group for C-2 addition onto the aziridine ring. In or-
der to determine the regiochemical outcome of the reaction, aziri-
dine 3 was reacted with a Gilman-type cuprate with n-BuLi as the
lithium source. In addition to an unidentified compound, the SN20
product was isolated in a ratio of 11:1 (stereochemistry unknown).
With the regiochemical preference of SN20, the substrate scope of
the reaction was examined. Aziridine 3 was subjected to similar
conditions with phenyllithium as the lithium source. A much lower
yield of the SN20 product was isolated in a stereochemical ratio of
88:1 (stereochemistry unknown, Scheme 5).
OTBS
OTBS
decomposition
N
THF/Me2S,
Ns
-78 °C
rt
2
n-BuLi
Me2SCuBr
recovered
N
starting material
Ts
THF/Me2S,
-78 °C
rt
4
Scheme 4. Unsucessful ring opening reactions using a Gilman-type cuprate.
With the inconsistent results of Gilman-type cuprates, Normant
reagents, a class of magnesium organocuprates were employed
with the hope of higher yields. A variety of allenes were generated
using different Grignard reagents (Fig. 3). Primary 20, 21, and 24,
secondary 21 and 22, and allyl 25 Normant reagents gave modest
to good yields of the SN20 product. Vinyl 26 and alkynyl 27 groups
were also able to add to the aziridine. Based on the literature of al-
lene formation using alkynyl aziridines, we believe that the addi-
tion occurs in an anti-fashion. Allene 19 was synthesized from
phenyllithium and the respective Grignard. Yields obtained with
the Normant reagent were much higher than those obtained with
the Gilman-type cuprates while the 1H NMR chemical shifts were
comparable thus indicating that the metal cation was not involved
in determining the stereochemistry.
n-BuLi
•
•
OTBS
NHTs
Me2SCuBr
THF/Me2S,
OTBS
OTBS
N
Ts
-78 °C
rt, 71%
3
18
19
Me2SCuBr
phenyllithium
OTBS
NHTs
N
THF/Me2S,
Ts
-78 °C
rt, 39%
3
Scheme 5. Unprecedented ring opening of a 2,2,3-trisubstituted aziridine.
reaction of aziridine 2 (Scheme 3), only the 4-toluenesulfonyl azi-
ridine 3 was used in the cuprate reactions. The ethynyl aziridine 3
could be capable of SN2P-addition, as the alkyne could also serve as
The stereochemistry was confirmed to be anti for the 3,5-dini-
trobenzoyl chloride derivative 19a of allene 19 that was crystal-
lized (Fig. 4).
R
•
H
R
MgBr
H
R
Me2SCuBr
OTBS
OTBS
NHTs
•
OTBS
NHTs
N
+
THF/Me2S,
Ts
-78 °C
rt
3
anti
syn
Br
CH3
•
H
H
H
H
H
•
OTBS
OTBS
NHTs
•
OTBS
NHTs
•
OTBS
NHTs
•
OTBS
NHTs
NHTs
81%, 9:1
54%, 12:1
80%, 24:1
85%, 9:1
70%, 12:1
20
21
22
23
24
H
H
H
H
•
OTBS
•
OTBS
NHTs
•
OTBS
•
OTBS
NHTs
NHTs
NHTs
62%, 11:1
52%, 49:1
44%, 25:1
73%, 53:1
25
26
27
19
Figure 3. Allenes synthesized with the Normant reagent.
NO2
O
NO2
Ph
O
H
•
NH
Ts
Figure 4. X-ray structure of the 3,5-dinitrobenzoyl derivative 19a of allene 19.

1236
B. T. Kelley, M. M. Joullié / Tetrahedron: Asymmetry 24 (2013) 1233–1239
R
CuIII
R
CuII
R
R
•
R
•
R
R
R
CuII
H
H
H
OTBS
NTs
OTBS
•
OTBS
NTs
reductive
elimination
oxidative
addition
quench
OTBS
OTBS
N
NHTs
30
N
Ts
3a
Ts
Mg
29
Mg
28
3a
R
CuI
Figure 5. Proposed mechanism for stereoselective allene formation.
A possible mechanism (Fig. 5) shows that the cuprate coordi-
nates to the alkyne on the opposite face of aziridine 3. After oxida-
tive addition, allene 28 is obtained. Reductive elimination of the
copper species and quenching completes the reaction to give the
various allene products.
The absolute stereochemistry of the allene was determined to
be P. Using a Newman projection viewing along the allene bond,
prioritization was assigned to the substituents on the front and
rear carbon of the projection. Tracing a 90° angle from the highest
priority substituent on the front carbon to the highest priority sub-
stituent on the back carbon results in a clockwise direction that is
defined as P (Fig. 6).
m = multiplet), and coupling constants. Proton decoupled 13C
NMR chemical shifts are reported in ppm from the solvent reso-
nance (CDCl3 77.0 ppm). Infrared spectra (IR) were obtained on a
Perkin–Elmer 281-B spectrometer. High resolution mass spectra
(HRMS) were obtained by Dr. Rakesh Kohli at the University of
Pennsylvania Mass Spectrometry Service Center on a Micromass
AutoSpec electrospray/chemical ionization spectrometer. Optical
rotations were measured with a Jasco P-1010 polarimeter. Single-
crystal X-ray diffraction structure determination was performed
by Dr. Patrick Carroll at the University of Pennsylvania. Melting
points (°C) were determined using a Thomas-Hoover melting point
apparatus and were uncorrected. The reaction solvents MeCN and
CH2Cl2 were distilled over calcium hydride. THF was distilled over
sodium/benzophenone and anhydrous dimethyl sulfide was pur-
chased from Aldrich and was used without further purification.
Flash chromatography was carried out using E. Merck silica gel
60 (240–400 mesh) using solvent systems listed under the individ-
ual experiments. Analytical thin-layer chromatography (TLC) was
performed on Merck silica gel (60F-254) plates (0.25 mm). All Grig-
nard and alkyllithium reagents were titrated with salicylaldehyde
phenylhydrazone prior to use. Copper(I) bromide dimethyl sulfide
complex was purchased from Aldrich and recrystallized to give
white-pixilated crystals prior to use.
4.1.1. N-((2R,3R)-1-((tert-Butyldimethylsilyl)oxy)-3-hydroxy-3-
methylpentan-2-yl)-4-methylbenzenesulfonamide 16
The tertiary alcohol 12 (2.58 g, 8.98 mmol) was dissolved in
CH2Cl2 (90 mL) under argon and was cooled to 0 °C. Triethylamine
(6.30 mL, 44.9 mmol), tert-butyldimethylsilyl chloride (1.90 g,
13.5 mmol), and 4-dimethylaminopyridne (110 mg, 0.898 mmol)
were added to the reaction sequentially. The reaction was stirred
overnight, at room temperature by allowing the ice-bath to melt.
The following day, the reaction was partitioned between H2O
(50 mL) and EtOAc (50 mL). The two layers were separated and
the aqueous layer was extracted with EtOAc (3 ꢀ 50 mL). The com-
bined organic layers were washed with 50 mL of brine. The organic
layers were dried over MgSO4, filtered, and concentrated. The
crude residue was purified by silica gel chromatography (50%
EtOAc–hexanes) to afford sulfonamide 16 as a thick oil (2.25 g,
62%). Rf 0.65 (50% EtOAc in hexanes); 1H NMR (500 MHz, CDCl3)
d 7.74 (2H, d, J = 8.5 Hz), d 7.26 (2H, d, J = 8.0 Hz), d 5.37 (1H, d,
J = 9.0 Hz), d 3.88 (1H, dd, J = 2.0, 10.5 Hz), d 3.69 (1H, dd, J = 2.5,
10.5 Hz), d 3.11 (1H, dt, J = 2.0, 8.5 Hz), d 2.39 (3H, s), d 1.31 (2H,
q, J = 7.5 Hz), d 1.16 (3H, s), d 0.84 (9H, s), d 0.58 (3H, t,
J = 7.5 Hz), d 0.02 (3H, s), d 0.00 (3H, s); 13C NMR (125 MHz, CDCl3)
d 143.2, 138.2, 129.5, 126.9, 75.3, 64.5, 57.3, 31.0, 23.8, 21.4, 17.9,
7.5, ꢁ5.8; IR (film): 3498(s), 3396(s), 3293(s), 2885(s), 2859(s),
1599(s) cmꢁ1; HRMS (EI) m/z calcd for C19H35NO4SSi (M+H)+
Figure 6. (a) The Newman projection of the derivative 19a viewed along the allene
bond. (b) X-ray structure of the 3,5-dinitrobenzoyl derivative of allene 19a viewed
through the allene bond.
3. Conclusion
In conclusion, we have synthesized nine new chiral allenes with
1,3-aminoalcohol substituents, via the ring opening reaction of
2,2,3-ethynyl aziridines with magnesium organocuprates in an
anti-fashion. We have determined their stereochemistry and ob-
tained the X-ray structure of a derivative to support our assign-
ment. These chiral allenes should find use as chiral building
blocks. We have also used a cyanide nucleophile to open a 2,2,3-
trisubstituted ethynyl aziridine in a stereospecific manner synthe-
sizing a quaternary center.
4. Experimental
4.1. General
402.2134; found: 402.2138; ½a D24
¼ ꢁ30:7 (c 2.68, CHCl3).
ꢂ
1H and 13C NMR Spectra were recorded at 500 MHz and
125 MHz, respectively on a Bruker DRX 500, unless otherwise
mentioned. 1H NMR chemical shifts are reported in parts per mil-
lion (ppm) from the solvent resonance (CDCl3 7.27 ppm). The data
are reported as follows: chemical shift, number of protons, multi-
plicity (s = singlet, d = doublet, t = triplet, quint = quintet, tt = trip-
let of triplets, q = quartet, dd = doublet of doublets, br = broad,
4.1.2. N-((2R,3R)-1-((tert-Butyldimethylsilyl)oxy)-3-hydroxy-3-
methylpent-4-yn-2-yl)-4-methylbenzenesulfonamide 11
The primary alcohol 10 (3.34 g, 11.8 mmol) was dissolved in
CH2Cl2 (118 mL) under argon and was cooled to 0 °C. Triethyl-
amine (8.20 mL, 58.9 mmol), tert-butyldimethylsilyl chloride

B. T. Kelley, M. M. Joullié / Tetrahedron: Asymmetry 24 (2013) 1233–1239
1237
(2.43 g, 17.7 mmol), and 4-dimethylaminopyridne (144 mg,
1.18 mmol) were added to the reaction sequentially. The reaction
was stirred overnight at room temperature by allowing the
ice-bath to melt. The following day, the reaction was partitioned
between H2O (60 mL) and EtOAc (60 mL). The two layers were sep-
arated and the aqueous layer was extracted with EtOAc
(3 ꢀ 60 mL). The combined organic layers were washed with
50 mL of brine. The organic layers were dried over MgSO4, filtered,
and concentrated. The crude residue was purified by silica gel
chromatography (50% acetone–hexanes) to afford product 11 as
an amorphous solid (5.12 g, quant). Rf 0.65 (50% acetone in hex-
anes); 1H NMR (500 MHz, CDCl3) d 7.76 (2H, d, J = 8.0 Hz), d 7.29
(2H, d, J = 8.0 Hz), d 5.06 (1H, d, J = 9.5 Hz), d 3.78–3.71 (2H, m), d
3.31–3.27 (1H, m), d 2.40 (3H, s), d 2.37 (1H, s), d 1.33 (3H, s), d
0.83 (9H, s), d 0.01 (6H, s); 13C NMR (125 MHz, CDCl3) d 143.6,
137.4, 129.6, 127.1, 84.3, 77.2, 73.4, 64.2, 59.1, 25.6, 21.4, 17.9,
ꢁ5.9, ꢁ6.0; IR (film): 3449(s), 3274(s), 2953(s), 2932(s), 2885(s),
2859(s), 1599(s) cmꢁ1; HRMS (EI) m/z calcd for C19H31NO4SSi
J = 7.5 Hz), d 0.84 (9H, s), d ꢁ0.02 (3H, s), d ꢁ0.04 (3H, s); 13C
NMR (125 MHz, CDCl3) d 143.4, 138.4, 129.3, 127.3, 60.8, 55.1,
53.5, 27.8, 25.7, 21.5, 18.1, 10.0, ꢁ5.5, ꢁ5.6; IR (film): 2955(s),
2930(s), 2883(s), 2858(s), 1599(s) cmꢁ1; HRMS (EI) m/z calcd for
C
19H33NO3SSi (M+Na)+ 406.1848; found: 406.1836; ½a 2D2
¼ þ14:7
ꢂ
(c 1.38, CHCl3).
4.1.5. N-((2S,3R)-1-((tert-Butyldimethylsilyl)oxy)-3-cyano-3-
methylpent-4-yn-2-yl)-2-nitrobenzenesulfonamide 17
The aziridine 2 (51.4 mg, 0.125 mmol) and potassium cyanide
(16.0 mg, 0.250 mmol) were placed in a flask and then dissolved
in dry MeCN (1.3 mL) at room temperature. 18-Crown-6
(66.0 mg, 0.250 mmol) was added in one portion and the reaction
was stirred at room temperature and monitored by TLC. After 2 h,
the reaction was partitioned between EtOAc (10 ml) and satd
NaHCO3 (5 mL). The two layers were separated and the aqueous
layer was extracted with EtOAc (10 mL). The combined organic
layers were dried over Na2SO4, filtered, and concentrated. The
crude product was purified by silica gel chromatography (30%
EtOAc–hexanes) to yield the ring opened product 17 as a pale
yellow oil (35.4 mg, 65%). Rf 0.38 (30% EtOAc–hexanes); 1H
NMR (500 MHz, CDCl3) d 8.16–8.14 (1H, m), d 7.94–7.91 (1H,
m), d 7.77–7.75 (2H, m), d 3.96 (1H, dd, J = 4.0, 9.0 Hz), d 3.86
(1H, t, J = 4.0 Hz), d 3.71 (1H, dd, J = 4.0, 9.0 Hz), d 2.47 (1H, s),
d 1.78 (3H, s), d 0.79 (9H, s), d ꢁ0.07 (3H, s), d ꢁ0.09 (3H, s);
13C NMR (125 MHz, CDCl3) d 147.7, 135.1, 133.7, 133.2, 130.3,
125.3, 77.9, 74.7, 62.9, 60.5, 34.8, 25.7, 25.3, 18.2, ꢁ5.8, ꢁ5.9;
IR (film): 3291(s), 3098(w), 2953(s), 2930(s), 2858(s), 2884(w),
1594(w), 1358(s) cmꢁ1; HRMS (EI) m/z calcd for C19H27N3O5SSi
(M+H)+ 398.1821; found: 398.1827; ½a 2D3
¼ ꢁ23:4 (c 3.19, CHCl3).
ꢂ
4.1.3. (2S,3S)-3-(((tert-Butyldimethylsilyl)oxy)methyl)-2-ethynyl-
2-methyl-1-tosylaziridine 3
The tertiary alcohol 11 (5.12 g, 11.8 mmol) was dissolved in dry
THF (118 mL) under argon and cooled to 0 °C. Triphenylphosphine
(4.64 g, 17.7 mmol) and diisopropyl azodicarboxylate (3.5 mL,
17.7 mmol) were added sequentially to the solution. The reaction
was stirred overnight at room temperature by allowing the ice-
bath to melt. The following day, the reaction was diluted with
60 mL of EtOAc and quenched with 30 mL of 1 M NaOH. The heter-
ogeneous solution was stirred for 20 min to completely hydrolyze
the diisopropyl azodicarboxylate. The two layers were separated
and the aqueous layer was extracted with EtOAc (3 ꢀ 20 mL). The
combined organic layers were washed with brine (30 mL). The
organic layer was dried over Na2SO4, filtered, and concentrated.
The crude residue was purified by silica gel chromatography
(100% CH2Cl2), to afford the aziridine as a colorless oil (3.76 g,
84%). Rf 0.64 (40% EtOAc in hexanes); 1H NMR (500 MHz, CDCl3)
d 7.85 (2H, d, J = 8.5 Hz), d 7.30 (2H, d, J = 8.5 Hz), d 3.80 (1H, dd,
J = 5.5, 11.5 Hz), d 3.58 (1H, dd, J = 6.5, 11.0 Hz), d 3.15 (1H, t,
J = 5.5 Hz), d 2.42 (3H, s), d 2.32 (1H, s), d 1.98 (3H, s), d 0.82 (9H,
s), d ꢁ0.01 (3H, s), d ꢁ0.05 (3H, s); 13C NMR (125 MHz, CDCl3) d
144.1, 137.4, 129.5, 127.5, 80.7, 71.6, 62.2, 52.1, 43.3, 25.7, 21.5,
20.0, 18.1, ꢁ5.5; IR (film): 3269(s), 2954(s), 2930(s), 2884(s),
2858(s), 1598(s) cmꢁ1; HRMS (EI) m/z calcd for C19H29NO3SSi
(MꢁH)ꢁ 436.1362; found: 436.1375;
½
a 1D9
ꢂ
¼ ꢁ125:0 (c 1.60,
CHCl3).
4.1.5.1. General procedure for cuprate additions.
To a flame
dried flask was added copper(I) bromide dimethyl sulfide complex
(2 equiv) and the flask was filled with argon. Freshly distilled THF
and dimethyl sulfide (1:1; ꢃ0.25 M) were then added to dissolve
the copper source. The flask was cooled to ꢁ78 °C and the respec-
tive (organolithium or Grignard) organometallic reagent (4 equiv)
was added dropwise and the solution was stirred at ꢁ78 °C for
30 min. Next, the aziridine (1 equiv) dissolved in dry THF was
added dropwise at ꢁ78 °C and the reaction was stirred at ꢁ78 °C
for 15 min then slowly warmed to room temperature and moni-
tored by TLC. After the reaction was complete, it was cooled to
0 °C, diluted with diethyl ether, and quenched with satd NH4Cl.
The two layers were separated and the aqueous layer was ex-
tracted with diethyl ether (2ꢀ). The combined organic layers were
dried over Na2SO4, filtered, and concentrated. The crude reaction
was purified by silica gel chromatography.
(M+H)+ 380.1716; found: 380.1718; ½a 2D4
¼ þ22:5 (c 0.97, CHCl3).
ꢂ
4.1.4. (2S,3S)-3-(((tert-Butyldimethylsilyl)oxy)methyl)-2-ethyl-2-
methyl-1-tosylaziridine 4
The tertiary alcohol 16 (2.25 g, 5.60 mmol) was dissolved in dry
THF (56 mL) under argon and cooled to 0 °C. Triphenylphosphine
(2.20 g, 8.40 mmol) and diisopropyl azodicarboxylate (1.6 mL,
8.40 mmol) were added sequentially to the solution. The reaction
was stirred overnight at room temperature by allowing the ice-
bath to melt. The following day, the reaction was diluted with
60 mL of EtOAc and quenched with 20 mL of 1 M NaOH. The heter-
ogeneous solution was stirred for 20 min to completely hydrolyze
the diisopropyl azodicarboxylate. The two layers were separated
and the aqueous layer was extracted with EtOAc (3 ꢀ 20 mL). The
combined organic layers were washed with brine (30 mL). The or-
ganic layer was dried over Na2SO4, filtered, and concentrated. The
crude residue was purified by silica gel chromatography (100%
CH2Cl2), to afford the aziridine as a colorless oil (1.19 g, 55%). Rf
0.73 (100% CH2Cl2); 1H NMR (500 MHz, CDCl3) d 7.84 (2H, d,
J = 8.0 Hz), d 7.28 (2H, d, J = 8.5 Hz), d 3.63 (1H, dd, J = 6.0,
11.3 Hz), d 3.55 (1H, dd, J = 6.0, 11.0 Hz), d 3.08 (1H, t, J = 6.0 Hz),
d 2.42 (3H, s), d 1.73 (3H, s), d 1.58–1.45 (2H, m), d 1.01 (3H, t,
4.1.6. N-((2S,4S)-1-((tert-Butyldimethylsilyl)oxy)-3-methylnona-
3,4-dien-2-yl)-4-methylbenzenesulfonamide 18
The general procedure using n-BuLi (1.8 M in hexanes) was fol-
lowed and the crude reaction was purified by silica gel chromatog-
raphy (10% ? 20% EtOAc–hexanes) to give the product as a pale
yellow oil (59.5 mg, 71%). Rf 0.48 (30% EtOAc in hexanes); 1H
NMR (500 MHz, CDCl3) d 7.73 (2H, d, J = 7.5 Hz), d 7.27 (2H, d,
J = 8.0 Hz), d 4.95 (1H, m), d 4.85 (1H, d, J = 7.0 Hz), d 3.63–3.59
(2H, m), d 3.57–3.54 (1H, m), d 2.42 (3H, s), d 1.95–1.91 (2H, m),
d 1.58 (3H, d, J = 7.5 Hz), d 1.33–1.28 (6H, m), d 0.91–0.88 (3H,
m), d 0.86 (9H, s), d 0.01 (3H, s), d ꢁ0.01 (3H, s); 13C NMR
(125 MHz, CDCl3) d 201.1, 143.1, 137.7, 129.4, 127.1, 98.2, 93.8,
64.4, 57.1, 31.4, 28.6, 25.8, 22.1, 18.2, 16.6, 13.8, ꢁ5.6, ꢁ5.6; IR
(film): 3279(s), 2955(s), 2929(s), 2858(s), 1966(w), 1599(s) cmꢁ1
;
HRMS (EI) m/z calcd for C23H39NO3SSi (M+Na)+ 460.2318; found:
460.2335; ½a 2D3
¼ þ63:9 (c 1.98, CHCl3).
ꢂ

1238
B. T. Kelley, M. M. Joullié / Tetrahedron: Asymmetry 24 (2013) 1233–1239
4.1.7. N-((2S,4S)-1-((tert-Butyldimethylsilyl)oxy)-3-methyl-5-
phenylpenta-3,4-dien-2-yl)-4-methylbenzenesulfonamide 19
The general procedure using a phenyllithium solution (1.8 M in
Et2O) was followed and the crude reaction was purified by silica gel
chromatography (10% acetone–hexanes) to give the product as a
pale yellow oil (39.5 mg, 39%).
The general procedure using a phenylmagnesium bromide
solution (1.0 M in THF) was followed and the crude reaction
was purified by silica gel chromatography (10% ? 20% ? 30%
7.27 (2H, d, J = 8.0 Hz), d 4.99 (1H, m), d 4.84 (1H, d, J = 7.0 Hz), d
3.65–3.61 (2H, m), d 3.57–3.54 (1H, m), d 2.41 (3H, s), d 2.38 (1H,
q, J = 7.5 Hz), d 1.75–1.68 (2H, m), d 1.62–1.56 (5H, m), d 1.55–
1.51 (3H, m), d 1.32–1.26 (2H, m), d 0.86 (9H, s), d 0.01 (3H, s), d
ꢁ0.01 (3H, s); 13C NMR (125 MHz, CDCl3) d 199.8, 143.0, 137.7,
129.4, 127.1, 99.1, 98.9, 64.5, 57.0, 39.2, 32.6, 25.8, 24.8, 21.4,
18.9, 16.7, ꢁ5.6; IR (film): 3280(s), 2953(s), 2829(s), 1965(w),
1599(w) cmꢁ1; HRMS (EI) m/z calcd for C24H39NO3SSi (M+Na)+
472.2318; found: 472.2307; ½a D22
þ 78:9 (c 1.95, CHCl3).
ꢂ
EtOAc–hexanes) to give the product as
a pale yellow oil
(70.1 mg, 73%). Rf 0.36 (30% EtOAc in hexanes); 1H NMR
(500 MHz, CDCl3) d 7.75 (2H, d, J = 8.0 Hz), d 7.37–7.21 (7H, m),
d 5.95 (1H, m), d 4.98 (1H, d, J = 7.5 Hz), d 3.82–3.80 (1H, m), d
3.73 (1H, dd, J = 4.5, 10.0 Hz), d 3.63 (1H, dd, J = 4.5, 10.0 Hz), d
2.43 (3H, s), d 1.79 (3H, d, J = 3.0 Hz), d 0.88 (9H, s), d 0.04 (3H,
s), d 0.00 (3H, s); 13C NMR (125 MHz, CDCl3) d 202.6, 143.3,
137.5, 134.3, 129.5, 128.5, 127.1, 127.1, 126.9, 115.3, 102.8,
96.9, 64.2, 57.3, 25.8, 21.5, 18.3, 16.1, ꢁ5.6; IR (film): 3276(s),
4.1.11. N-((2S,4S)-1-((tert-Butyldimethylsilyl)oxy)-3-methyl-
hepta-3,4-dien-2-yl)-4-methylbenzenesulfonamide 23
The general procedure using an ethylmagnesium bromide solu-
tion (1.0 M in THF) was followed and the crude reaction was puri-
fied by silica gel chromatography (30% EtOAc–hexanes) for give the
product as a colorless oil (63.9 mg, 70%). Rf 0.68 (30% EtOAc in hex-
anes); 1H NMR (500 MHz, CDCl3) d 7.74–7.72 (2H, m), d 7.28–7.27
(2H, m), d 5.06–5.02 (1H, m), d 4.85 (1H, d, J = 7.0 Hz), d 3.66–3.59
(2H, m), d 3.58–3.54 (1H, m), d 2.42 (3H, s), d 1.98–1.92 (2H, m), d
1.60 (3H, d, J = 7.5 Hz), d 0.96 (3H, t, J = 7.5 Hz), d 0.85 (9H, s), d
ꢁ0.01 (3H, s), d ꢁ0.01 (3H, s); 13C NMR (125 MHz, CDCl3) d
200.8, 143.1, 137.8, 129.4, 127.1, 99.0, 95.6, 64.5, 57.1, 25.8, 22.0,
21.5, 18.2, 16.7, 13.6, ꢁ5.6, ꢁ5.6; IR (film): 3279(s), 2957(s),
2930(s), 2897(s), 2884(s), 2858(s), 1599(w) cmꢁ1; HRMS (EI) m/z
2953(s), 2928(s), 2884(s), 2857(s), 1954(w), 1599(w) cmꢁ1
;
HRMS (EI) m/z calcd for C25H35NO3SSi (M+H)+ 458.2185; found:
458.2180; ½a 2D3
¼ þ205 (c 3.30, CHCl3).
ꢂ
4.1.8. N-((2S,4S)-1-((tert-Butyldimethylsilyl)oxy)-3-methylhexa-
3,4-dien-2-yl)-4-methylbenzenesulfonamide 20
calcd for
¼ þ65:8 (c 2.48, CHCl3).
C
21H35NO3SSi (M+H)+ 410.2185; found: 410.2188;
The general procedure using a methylmagnesium bromide
solution (3.0 M in Et2O) was followed and the crude reaction was
purified by silica gel chromatography (10% ? 20% ? 30% EtOAc–
hexanes) to give the product as a pale yellow oil (41.6 mg, 54%).
Rf 0.67 (30% EtOAc in hexanes); 1H NMR (500 MHz, CDCl3) d 7.73
(2H, d, J = 8.5 Hz), d 7.28 (2H, d, J = 7.0 Hz), d 4.98–4.92 (1H, m), d
4.89 (1H, d, J = 7.0 Hz), d 3.64–3.60 (1H, m), d 3.57–3.54 (1H, m),
d 2.42 (3H, s), d 1.60 (3H, d, J = 7.0 Hz), d 1.57 (3H, d, J = 3.0 Hz), d
0.85 (9H, s), d ꢁ0.01 (3H, s), d ꢁ0.01 (3H, s); 13C NMR (125 MHz,
CDCl3) d 202.1, 143.1, 137.7, 129.4, 127.1, 97.6, 88.2, 64.2, 57.2,
25.8, 21.5, 18.2, 16.3, 14.4, ꢁ5.6, ꢁ5.6; IR (film): 3279(s), 2953(s),
2929(s), 2858(s), 1599(w) cmꢁ1; HRMS (EI) m/z calcd for C20H33-
½ ꢂ
a 2D3
4.1.12. N-((2S,4S)-6-(3-Bromophenyl)-1-((tert-butyldimethyl-
silyl)oxy)-3-methylhexa-3,4-dien-2-yl)-4-methylbenzenesulf-
onamide 24
The general procedure using a 3-bromobenzylmagnesium bro-
mide solution (0.25 M in Et2O) was followed and the crude reaction
was purified by silica gel chromatography (30% EtOAc–hexanes) to
give the product as a colorless oil (86.6 mg, 81%). Rf 0.57 (30%
EtOAc in hexanes); 1H NMR (500 MHz, CDCl3) d 7.70 (2H, d,
J = 8.0 Hz), d 7.36–7.34 (1H, m), d 7.32–7.30 (1H, m), d 7.25–7.22
(2H, m), d 7.19–7.16 (1H, m), d 7.11–7.10 (1H, m), d 5.09–5.05
(1H, m), d 4.88 (1H, d, J = 7.0 Hz), d 3.70–3.66 (1H, m), d 3.51 (2H,
d, J = 5.5 Hz), d 3.25 (2H, d, J = 7.5 Hz), d 2.40 (3H, s), 1.63 (3H, d,
J = 3.0 Hz), d 0.85 (9H, s), d 0.01 (3H, s), d ꢁ0.01 (3H, s); 13C NMR
(125 MHz, CDCl3) d 202.2, 143.2, 142.5, 137.6, 131.4, 130.0,
129.5, 127.1, 127.0, 122.4, 99.2, 92.1, 64.2, 57.4, 35.2, 25.8, 18.2,
16.2; IR (film): 3278(s), 2953(s), 2928(s), 2898(w), 2857(s),
1969(s), 1597(s), 1568(s) cmꢁ1; HRMS (EI) m/z calcd for C26H36-
NO3SSi (M+H)+ 396.2029; found: 396.2033; ½a 2D4
¼ þ59:4 (c 1.63,
ꢂ
CHCl3).
4.1.9. N-((2S,4S)-1-((tert-Butyldimethylsilyl)oxy)-3,6-dimethyl-
hepta-3,4-dien-2-yl)-4-methylbenzenesulfonamide 21
The general procedure using an isopropylmagnesium bromide
solution (2.9 M in 2-methyltetrahydrofuran) was followed and
the crude reaction was purified by silica gel chromatography
(30% EtOAc–hexanes) to give the product as a colorless oil
(74.8 mg, 80%). Rf 0.61 (30% EtOAc in hexanes); 1H NMR
BrNO3SSi (M+H)+ 550.1447; found: 550.1450; ½a 2D0
¼ þ70:8 (c
ꢂ
1.68, CHCl3).
(500 MHz, CDCl3)
d 7.73 (2H, d, J = 8.0 Hz), d 7.28 (2H, d,
J = 8.5 Hz), d 4.98 (1H, m), d 4.84 (1H, d, J = 7.5 Hz), d 3.66–3.62
(2H, m), d 3.57–3.54 (1H, m), d 2.41 (3H, s), d 2.27–2.19 (1H, m),
d 1.60 (3H, d, J = 3.0 Hz), d 0.96 (3H, s), d 0.85 (3H, s), d 0.85 (9H,
s), d 0.01 (3H, s), d ꢁ0.01 (3H, s); 13C NMR (125 MHz, CDCl3) d
199.5, 143.1, 137.8, 129.4, 127.1, 101.4, 99.7, 64.6, 57.0, 28.1,
25.8, 22.6, 21.4, 18.2, 16.8, ꢁ5.6, ꢁ5.6; IR (film): 3280(s), 2957(s),
2929(s), 2884(s), 2559(s), 1599(w) cmꢁ1; HRMS (EI) m/z calcd for
4.1.13. N-((2S,4S)-1-((tert-Butyldimethylsilyl)oxy)-3-methylocta-
3,4,7-trien-2-yl)-4-methylbenzenesulfonamide 25
The general procedure using an allylmagnesium bromide
solution (1.0 M in Et2O) was followed and the crude reaction was
purified by silica gel chromatography (10% ? 20% ? 30% EtOAc–
hexanes) to give the product as a colorless oil (50.7 mg, 62%). Rf
0.63 (30% EtOAc in hexanes); 1H NMR (500 MHz, CDCl3) d 7.73
(2H, m), d 7.27 (2H, m), d 5.84–5.76 (1H, m), d 5.08–4.97 (3H, m),
d 4.86 (1H, d, J = 7.0 Hz), d 3.67–3.64 (1H, m), d 3.62–3.59 (1H,
m), d 3.58–3.54 (1H, m), d 2.69 (2H, tt, J = 1.5, 6.5 Hz), 2.42 (3H,
s), d 1.60 (3H, d, J = 3.0 Hz), d 0.85 (9H, s), d 0.01 (3H, s), d ꢁ0.01
(3H, s); 13C NMR (125 MHz, CDCl3) d 201.8, 143.1, 137.7, 136.4,
129.4, 127.2, 115.3, 98.9, 91.7, 64.4, 57.2, 33.2, 25.8, 21.4, 18.2,
16.4, ꢁ5.6, ꢁ5.6; IR (film): 3279(s), 2953(s), 2929(s), 2898(s),
2857(s), 1967(w), 1639(w), 1599(w) cmꢁ1; HRMS (EI) m/z calcd
C
22H37NO3SSi (M+Na)+ 446.2161; found: 446.2144; ½a 2D2
¼ þ76:7
ꢂ
(c 1.51, CHCl3).
4.1.10. N-((2S,4S)-1-((tert-Butyldimethylsilyl)oxy)-5-cyclopentyl-
3-methylpenta-3,4-dien-2-yl)-4-methylbenzenesulfonamide 22
The general procedure using a cyclopentylmagnesium bromide
solution (2.0 M in THF) was followed and the crude reaction was
purified by silica gel chromatography (30% EtOAc–hexanes) to give
the product as a colorless oil (80.3 mg, 85%). Rf 0.63 (30% EtOAc in
hexanes); 1H NMR (500 MHz, CDCl3) d 7.72 (2H, d, J = 8.0 Hz), d
for
½ ꢂ
C
22H35NO3SSi (M+H)+ 422.2185; found: 422.2191;
¼ þ79:9 (c 0.90, CHCl3).
a 2D2

B. T. Kelley, M. M. Joullié / Tetrahedron: Asymmetry 24 (2013) 1233–1239
1239
4.1.14. N-((2S,4S)-1-((tert-Butyldimethylsilyl)oxy)-3-methyl-
hepta-3,4,6-trien-2-yl)-4-methylbenzenesulfonamide 26
monitored by TLC. After completion of the reaction, the solution
was partitioned between EtOAc (10 mL) and H2O (5 mL). The two
layers were separated and the aqueous layer was extracted with
EtOAc (10 mL). The combined organic layers were dried over Na2-
SO4, filtered, and concentrated. The crude product was purified
by silica gel chromatography (10% ? 20% ? 30% EtOAc–hexanes)
to give product 19a as a colorless foam (105 mg, 69%). Rf 0.35
(30% EtOAc in hexanes); 1H NMR (500 MHz, CDCl3) d 9.13 (1H, t,
J = 2.0 Hz), d 8.94 (2H, d, J = 2.0 Hz), d 7.77 (2H, d, J = 8.5 Hz), d
7.27 (2H, d, J = 8.0 Hz), d 7.09–7.08 (4H, m), d 7.05–7.01 (1H, m),
d 6.15 (1H, quint, J = 2.5 Hz), d 5.09 (1H, d, J = 9.0 Hz), d 4.56 (1H,
dd, J = 5.0, 11.0 Hz), d 4.48 (1H, dd, J = 6.0, 11.0 Hz), d 4.27–4.23
(1H, m), d 2.39 (3H, s), d 1.75 (3H, d, J = 3.0 Hz); 13C NMR
(125 MHz, CDCl3) d 202.3, 162.2, 148.4, 143.8, 137.6, 133.2,
133.1, 129.7, 129.4, 128.5, 127.5, 126.9, 126.8, 122.2, 101.3, 98.2,
66.7, 54.7, 21.5, 16.8; IR (film): 3285 (s), 3102 (s), 2923 (s), 1736
(s), 1546 (s) cmꢁ1; HRMS (EI) m/z calcd for C26H23N3O8S (M+H)+
The general procedure using a vinylmagnesium bromide solu-
tion (0.69 M in Et2O) was followed and the crude reaction was
purified by silica gel chromatography (10% ? 20% ? 30% EtOAc–
hexanes) to give the product as a colorless oil (43.0 mg, 52%). Rf
0.58 (30% EtOAc in hexanes); 1H NMR (500 MHz, CDCl3) d 7.77
(2H, m), d 7.30–7.28 (2H, m), d 6.12–6.04 (1H, m), d 5.64–5.61
(1H, m), d 5.16–5.10 (1H, m), d 5.00–4.92 (2H, m), d 3.72–3.69
(1H, m), d 3.57–3.54 (1H, m), d 2.42 (3H, s), 1.64 (2H, d,
J = 3.0 Hz), d 1.58 (1H, t, J = 3.0 Hz), d 0.85 (9H, s), d 0.00 (3H, s), d
ꢁ0.02 (3H, s); 13C NMR (125 MHz, CDCl3, both diastereomers) d
206.3, 204.8, 143.2, 143.2, 137.7, 137.6, 132.8, 129.5, 129.4,
127.2, 127.1, 116.1, 99.8, 97.5, 96.7, 64.0, 63.9, 57.2, 56.8, 25.8,
25.7, 21.5, 18.2, 18.1, 16.1, 15.8, ꢁ5.6, ꢁ5.6; IR (film): 3276(s),
2954(s), 2929(s), 2857(s), 1954(w), 1615(w), 1599(w) cmꢁ1; HRMS
(EI) m/z calcd for C21H33NO3SSi (M+Na)+ 430.1848; found:
430.1846; ½a 2D2
ꢂ
þ 57:0 (c 0.99, CHCl3).
538.1284; found: 538.1273;
½
a 2D3
ꢂ
¼ þ185:6 (c 1.09, CHCl3);
mp = 58–61 °C.
4.1.15. N-((2S,4S)-1-((tert-Butyldimethylsilyl)oxy)-3-methylhepta-
3,4-dien-6-yn-2-yl)-4-methylbenzenesulfonamide 27
Acknowledgments
The general procedure using an ethynylmagnesium bromide
solution (0.5 M in THF) was followed and the crude reaction was
purified by silica gel chromatography (30% EtOAc–hexanes) to give
the product as a colorless oil (35.5 mg, 44%). Rf 0.39 (30% EtOAc in
hexanes); 1H NMR (500 MHz, CDCl3) d 7.76 (2H, d, J = 8.0 Hz), d
7.30 (2H, d, J = 8.0 Hz), d 5.14–5.12 (1H, m), d 4.98 (1H, d,
J = 8.0 Hz), d 3.79–3.75 (1H, m), d 3.62 (1H, dd, J = 4.5, 10.0 Hz), d
3.56 (1H, dd, J = 4.5, 10.0 Hz), d 2.83 (1H, d, J = 2.5 Hz), d 2.43
(3H, s), d 1.65 (3H, d, J = 3.0 Hz), d 0.85 (9H, s), d 0.02 (3H, s), d
ꢁ0.01 (3H, s); 13C NMR (125 MHz, CDCl3) d 210.8, 143.4, 137.6,
129.6, 127.2, 101.4, 78.4, 76.6, 63.6, 56.8, 25.8, 21.5, 18.2, ꢁ5.5;
IR (film): 3287(s), 2954(s), 2929(s), 2884(s), 1599(w) cmꢁ1; HRMS
Financial support for this research was provided by the NSF
(CHE-0951394). The authors thank Dr. Pat Carroll for the determi-
nation of the X-ray structure (CCDC No. 959451) of the allene
derivative. We would also like to thank Dr. Rakesh Kohli for assis-
tance in securing and interpreting mass spectra.
References
1. (a) Ohno, H.; Toda, A.; Miwq, Y.; Taga, T.; Fujii, N.; Ibuka, T. Tetrahedron Lett.
1999, 40, 349–352; (b) Ohno, H.; Toda, A.; Fuji, N.; Takemoto, Y.; Tanaka, T.;
Ibuka, T. Tetrahedron 2000, 56, 2811–2820; (c) Elsevier, C. J.; Vermeer, P. J. Org.
Chem. 1989, 54, 3726–3730; (d) Elsevier, C. J.; Mooiweer, H. H. J. Org. Chem.
1987, 52, 1536–1539; (e) Chemla, F.; Ferreira, F. Curr. Org. Chem. 2002, 6, 539–
570; (f) Hoffman-Roder, A.; Krause, N. Angew. Chem., Int. Ed. 2002, 41, 2933–
2935.
2. (a) Yu, S.; Ma, S. Angew. Chem., Int. Ed. 2012, 51, 3074–3112; (b) Ryvera-
Fuentes, P.; Diederich, F. Angew. Chem., Int. Ed. 2012, 51, 2818–2828.
3. (a) Walbrick, J. M.; Wilson, J. W. J.; Jones, W. M. J. Am. Chem. Soc. 1968, 90,
2895–2901; (b) Tejedor, D.; Méndez-Abt, G.; Cotos, L.; Garcia-Tellado, F. Chem.
Soc. Rev. 2013, 42, 458–471.
(EI) m/z calcd for
C
21H31NO3SSi (M+H)+ 406.1872; found:
¼ þ113:6 (c 1.38, CHCl3).
406.1878; ½a 2D4
ꢂ
4.1.16. (2S,4S)-3-Methyl-2-((4-methylphenyl)sulfonamido)-5-
phenylpenta-3,4-dien-1-yl 3,5-dinitrobenzoate 19a
Allene 19 (130 mg; 0.285 mmol) was dissolved in THF (2.8 mL)
4. (a) Li, A.-H.; Zhou, Y.-G.; Dai, L.-X.; Hou, X.-L.; Xia, L.-J.; Lin, L. J. Org. Chem. 1998,
63, 4338–4348; (b) Li, A.-H.; Zhou, Y.-G.; Dai, L.-X.; Hou, X.-L.; Xia, L.-J.; Lin, L.
Angew. Chem., Int. Ed. 1997, 36, 1317–1319.
5. Florio, S.; Troisi, L.; Capriati, V.; Suppa, G. Eur. J. Org. Chem. 2000, 3793–3797.
6. (a) Ohno, H.; Toda, A.; Takemoto, Y.; Fuji, N.; Ibuka, T. J. Chem. Soc., Perkin Trans.
I 1999, 2949–2962; (b) Ohno, H.; Toda, A.; Fujii, N.; Ibuka, T. Tetrahedron:
Asymmetry 1998, 9, 3929–3933.
and cooled to 0 °C. Tetrabutylammonium fluoride (569 lL; 1.0 M in
THF) was then added to the solution and the reaction was stirred at
0 °C and monitored by TLC. After completion of the reaction, it was
diluted with EtOAc (10 mL) and quenched with satd NH4Cl (5 mL).
The two layers were separated and the aqueous layer was ex-
tracted with EtOAc (10 mL). The combined organic layers were
washed with brine. The organic layer was dried over Na2SO4, fil-
tered, and concentrated. The crude alcohol was used without fur-
ther purification. The alcohol was re-dissolved in CH2Cl2 (2.8 mL)
and cooled to 0 °C. 3,5-Dinitrobenzoyl chloride (197 mg,
7. Ohno, H.; Ando, K.; Hamaguchi, H.; Takeoka, Y.; Tanaka, T. J. Am. Chem. Soc.
2002, 124, 15146–15402.
8. Ferreira, F.; Audouin, M.; Chemla, F. Chem. Eur. J. 2005, 11, 5269–5278.
9. He, Z.; Yudin, A. K. Angew. Chem., Int. Ed. 2010, 49, 1607–1610.
10. (a) Li, P.; Forbeck, E. M.; Evans, C. D.; Joullié, M. M. Org. Lett. 2006, 8, 5105–
5107; (b) Kelley, B. T.; Joullié, M. M. Org. Lett. 2010, 12, 4244–4247; (c) Forbeck,
E. M.; Evans, C. D.; Gilleran, J. A.; Li, P.; Joullié, M. M. J. Am. Chem. Soc. 2007, 129,
14463–14469.
0.854 mmol) and N,N-diisopropylethylamine (148
lL, 0.854 mmol)
were then added sequentially to the solution and the reaction was