Organocatalytic asymmetric allylic alkylation of sulfonylimidates with Morita-Baylis-Hillman carbonates

Article abstract of DOI:10.1007/s11426-010-4137-2

The asymmetric allylic alkylation reaction of sulfonylimidates with various Morita-Baylis-Hillman (MBH) carbonates was accomplished by the catalysis of commercially available cinchona alkaloids catalyst (DHQD)₂AQN. The corresponding allylic alk

Full text of DOI:10.1007/s11426-010-4137-2

SCIENCE CHINA
Chemistry
January 2011 Vol.54 No.1: 81–86
doi: 10.1007/s11426-010-4137-2
• ARTICLES •
· SPECIAL TOPIC · The Frontiers of Chemical Biology and Synthesis
Organocatalytic asymmetric allylic alkylation of sulfonylimidates
with Morita-Baylis-Hillman carbonates
PENG Jing, CUI HaiLei & CHEN YingChun*
Key Laboratory of Drug-Targeting and Drug Delivery System, Ministry of Education; Department of Medicinal Chemistry,
West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Received July 28, 2010; accepted August 24, 2010
The asymmetric allylic alkylation reaction of sulfonylimidates with various Morita-Baylis-Hillman (MBH) carbonates was ac-
complished by the catalysis of commercially available cinchona alkaloids catalyst (DHQD)2AQN. The corresponding allylic
:
alkylation products were obtained in good yields with high stereoselectivities (up to 99% ee, 89 11 dr).
organocatalysis, asymmetric allylic alkylation, sulfonylimidates, Morita-Baylis-Hillman carbonates, cinchona alkaloids
cation of sulfonylimidates is still far from satisfaction.
1 Introduction
Therefore, it is desirable to find out a mild and efficient
process for the direct asymmetric modification of sulfon-
ylimidates.
Imidates, also known as imidoates, imidic acid esters, or
imido esters, are known to be important pharmacophores
and useful synthetic building blocks [1–3]. Recently, the
transformations of imidates have received increasing atten-
tion and much efforts have been devoted to this field [4–10].
Kobayashi group reported the first example of sulfonylimi-
dates acting as nucleophiles in catalytic addition reaction
with imines [4]. Later, a Pd/Brønsted base-catalyzed ap-
proach to the decarboxylative allylation of sulfonylimidates
has been developed [5, 6]. In addition, the first example of a
catalytic asymmetric Mannich-type reaction of a sulfon-
ylimidate has been reported, which was catalyzed by alka-
line earth metals, but only moderate enantioselectivity was
observed [7]. A notable example was reported by Barbas et
al. who developed a stereoselective organocatalytic Michael
addition of N-tosylimidates to α,β-unsaturated aldehydes
catalyzed by trialkylsilyl-protected α,α-diarylprolinol [8].
However, there were limitations for the chemical yields,
diastereomeric ratios and generality of the substrates. The
optimization of the asymmetric variant as well as the appli-
Recently, the allylic alkylation of Morita-Baylis-Hillman
(MBH) adducts catalyzed by a metal-free organic Lewis
base has emerged as an attractive strategy to prepare multi-
functional compounds [11–22]. Our group have also re-
ported that modified cinchona alkaloids can act as excellent
organocatalysts for asymmetric allylic alkylation (AAA)
reactions with MBH carbonates [23–28]. On the other hand,
the deprotonation of α-position from a carbonyl compound
and the subsequent nucleophilic addition of the formed
enolate is a fundamental sequence of transformations in
Scheme 1 Proposed allylic alkylation of sulfonylimidates with MBH
carbonates catalyzed by tertiary amine.
*Corresponding author (email: ycchenhuaxi@yahoo.com.cn)
© Science China Press and Springer-Verlag Berlin Heidelberg 2011
chem.scichina.com
www.springerlink.com

82
Peng J, et al. Sci China Chem January (2011) Vol.54 No.1
Compound 3d. 98% yield; 87:13 dr; [α]D20 = −130.3 (c =
0.40 in CHCl3); 95% ee, determined by HPLC analysis
[Daicel chiralpak IC, n-hexane/i-PrOH = 95/5, 1.0 mL/min,
λ = 254 nm, t(major) = 19.80 min, t(minor) = 22.14 min];
1H NMR (400 MHz, CDCl3): δ 7.48–7.43 (m, 4H), 7.32–
7.30 (m, 2H), 7.28–7.08 (m, 4H), 7.12–7.02 (m, 6H), 6.87
(d, J = 8.0 Hz, 2H), 6.58 (s, 1H), 6.48 (s, 1H), 5.47 (d, J =
12.0 Hz, 1H), 4.90 (d, J = 12.0 Hz, 1H), 3.71 (s, 3H), 2.32
(s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 172.1, 166.6,
151.5, 143.2, 141.5, 138.3, 137.2, 135.1, 132.7, 129.9,
129.4, 129.2, 129.1, 128.6, 128.3, 128.1, 126.4, 126.3,
125.6, 121.0, 53.4, 52.2, 49.1, 21.4 ppm; ESI-HRMS: calcd
for C32H28ClNO5S+Na 596.1274, found 596.1293.
synthetic organic chemistry. In general, a stoichiometric
amount of base is necessary in the deprotonation step. So
we anticipated that, as outlined in Scheme 1, the deprotona-
tion of the α-H of the sulfonylimidates by the tert-butoxy
anion generated in suit would occur, and the subsequent
asymmetric allylic alkylation would follow to deliver valu-
able chiral sulfonylimidate derivatives.
2 Experimental
2.1 General methods
NMR spectra were recorded with tetramethylsilane as the in-
ternal standard. TLC was performed on glass-backed silica
plates. Column chromatography was performed using silica
gel (200–300 mesh) eluting with ethyl acetate and petroleum
Compound 3e. 82% yield; 87:13 dr; [α]D20 = −107.3 (c =
0.95 in CHCl3); 97% ee, determined by HPLC analysis
[Daicel chiralpak AD, n-hexane/i-PrOH = 90/10, 1.0 mL/
min, λ = 254 nm, t(major) = 10.05 min, t(minor) = 14.15
1
ether. H NMR spectra were recorded at 400 MHz (Varian),
1
and 13C NMR spectra were recorded at 50 MHz or 100 MHz
(Varian). Chemical shifts were reported in ppm downfield
from CDCl3 (δ 7.27 ppm) for 1H NMR and relative to the cen-
tral CDCl3 resonance (δ 77.0 ppm) for 13C NMR spectros-
copy. Coupling constants were given in Hz. Optical rotations
were measured at 589 nm, 20 °C. Enantiomeric excess was
determined by HPLC analysis on Chiralpak AS, IC, AD and
Chiralcel OD columns. Toluene was distilled from CaH2. All
other chemicals were used without purification as commer-
cially available. Cinchona alkaloids catalysts (DHQD)2PHAL,
(DHQD)2PYR, (DHQD)2AQN, (DHQ)2AQN were purchased
from Aldrich Chemical Company.
min]; H NMR (400 MHz, CDCl3): δ 7.50–7.43 (m, 4H),
7.32–7.28 (m, 2H), 7.23–7.15 (m, 4H), 7.13–7.05 (m, 2H),
7.00–6.87 (m, 6H), 6.56 (s, 1H), 6.47 (s, 1H), 5.49 (d, J =
12.0 Hz, 1H), 4.89 (d, J = 12.0 Hz, 1H), 3.70 (s, 3H), 3.33
(s, 3H), 2.19 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ
172.5, 166.8, 151.6, 143.1, 141.8, 138.4, 137.6, 135.5,
129.3, 129.3, 129.1, 128.6, 128.4, 127.9, 127.8, 127.6,
127.2, 126.3, 125.8, 125.4, 123.6, 121.1, 53.7, 52.2, 49.5,
21.4, 21.3 ppm; ESI-HRMS: calcd for C33H31NO5S+Na
576.1821, found 576.1812.
Compound 3f. 86% yield; 86:14 dr; [α]D20 = −120.0 (c =
0.95 in CHCl3); 98% ee, determined by HPLC analysis
[Daicel Chiralcel OD, n-hexane/i-PrOH = 95/5, 1.0 mL/min,
λ = 254 nm, t(major) = 11.20 min, t(minor) = 15.59 min];
1H NMR (400 MHz, CDCl3): δ 7.51–7.43 (m, 4H), 7.32–
7.29 (m, 2H), 7.24–7.15 (m, 4H), 7.10 (d, J = 8.0 Hz, 2H),
7.00 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 8.0 Hz, 2H), 6.64 (d,
J = 8.8 Hz, 2H), 6.53 (s, 1H), 6.44 (s, 1H), 5.46 (d, J = 11.2
Hz, 1H), 4.87 (d, J = 12.0 Hz, 1H), 3.70 (s, 3H), 3.69 (s,
3H), 2.32 (s, 3H) ppm; 13C NMR (50 MHz, CDCl3): δ 172.6,
166.9, 158.4, 151.7, 143.1, 142.2, 138.5, 135.7, 130.6,
130.1, 129.6, 129.4, 129.1, 128.9, 128.5, 127.8, 126.3,
124.9, 121.1, 113.6, 55.1, 53.8, 52.1, 49.0, 21.4 ppm;
ESI-HRMS: calcd for C33H31NO6S+Na 592.1770, found
592.1757.
2.2 General procedure for asymmetric allylic alkyla-
tion of sulfonylimidates 1 and Morita-Baylis-Hillman
carbonates 2
A mixture of sulfonylimidate 1 (0.1 mmol), Morita-Baylis-
Hillman carbonate 2 (0.2 mmol) and (DHQD)2AQN (10
mol%) in dry toluene (1.0 mL) were stirred at 50 °C for a
specified reaction time. Then the solvent was removed un-
der reduced pressure and the residue was purified by flash
chromatography on silica gel (petroleum ether/ethyl acetate)
to give the product 3.
Compound 3c. 98% yield; 87:13 dr; [α]D20 = −105.9 (c =
1.0 in CHCl3); 96% ee, determined by HPLC analysis [Dai-
cel chiralpak AD, n-hexane/i-PrOH = 90/10, 1.0 mL/min, λ =
Compound 3g. 94% yield; 89:11 dr; [α]D20 = −69.5 (c =
0.44 in CHCl3); 93% ee, determined by HPLC analysis
[Daicel chiralpak IC, n-hexane/i-PrOH = 90/10, 1.0 mL/min,
λ = 254 nm, t(major) = 16.57 min, t(minor) = 18.39 min];
1H NMR (400 MHz, CDCl3): δ 7.47–7.42 (m, 5H), 7.35–
7.30 (m, 3H), 7.28–7.24 (m, 2H), 7.22–7.13 (m, 3H), 6.96–
6.95 (m, 2H), 6.94–6.61 (m, 3H), 6.49 (s, 1H), 6.39 (s, 1H),
5.55 (br s, 2H), 3.72 (s, 3H), 2.33 (s, 3H) ppm; 13C NMR
(50 MHz, CDCl3): δ 172.0, 166.6, 151.6, 143.1, 138.4, 138.0,
134.2, 133.0, 130.1, 129.7, 129.4, 129.1, 128.8, 128.4, 128.2,
128.1, 127.4, 126.5, 126.3, 126.0, 121.2, 53.5, 52.1, 49.6,
21.4 ppm; ESI-HRMS: calcd for C32H28BrNO5S+H 618.0950,
1
254 nm, t(major) = 12.06 min, t(minor) = 17.96 min]; H
NMR (400 MHz, CDCl3): δ 7.49–7.44 (m, 4H), 7.33–7.29
(m, 2H), 7.26–7.21 (m, 4H), 7.15–7.06 (m, 6H), 6.88 (d, J =
8.0 Hz, 2H), 6.57 (s, 1H), 6.49 (s, 1H), 5.52 (d, J = 12.0 Hz,
1H), 4.93 (d, J = 12.0 Hz, 1H), 3.71 (s, 3H), 2.33 (s, 3H)
ppm; 13C NMR (100 MHz, CDCl3): δ 172.4, 166.8, 151.6,
143.1, 141.8, 138.5, 135.4, 129.3, 129.3, 129.1, 128.6,
128.5, 128.1, 127.9, 127.3, 126.8, 126.3, 126.0, 125.3, 120.9,
53.6, 52.2, 49.7, 21.4 ppm; ESI-HRMS: calcd for
C27H27NO5S+Na 500.1508, found 500.1517.

Peng J, et al. Sci China Chem January (2011) Vol.54 No.1
83
found 618.0944.
507.1742.
Compound 3h. 99% yield; 67:33 dr; [α]D20 = −25.1 (c =
0.52 in CHCl3); 90% ee, determined by HPLC analysis
[Daicel chiralpak IC, n-hexane/i-PrOH = 95/5, 1.0 mL/min,
λ = 254 nm, t(major) = 29.11 min, t(minor) = 26.98 min];
1H NMR (400 MHz, CDCl3): δ 7.54–7.53 (m, 2H),
7.50–7.48 (m, 2H), 7.37–7.26 (m, 7H), 7.25–7.16 (m, 2H),
7.15–7.11 (m, 2H), 6.85 (d, J = 8.0 Hz, 2H), 6.59 (s, 1H),
6.47 (s, 1H), 5.89 (d, J = 2.8 Hz, 1H), 5.07 (d, J = 12.0 Hz,
1H), 3.76 (s, 3H), 2.34 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3): δ 171.4, 166.7, 151.3, 143.1, 141.9, 138.8, 129.6,
129.3, 129.1, 128.9, 128.8, 128.6, 128.1, 127.7, 126.4,
126.3, 121.0, 110.1, 108.1, 52.3, 51.9, 42.9, 21.4 ppm;
ESI-HRMS: calcd for C30H27NO6S+H 530.1637, found
530.1649.
Compound 3l, diastereomer 1. 34% yield; [α]D
=
20
−11.1 (c = 0.35 in CHCl3); 81% ee, determined by HPLC
analysis [Daicel chiralpak AD, n-hexane/i-PrOH = 80/20,
1.0 mL/min, λ = 254 nm, t(major) = 10.52 min, t(minor) =
1
9.27 min]; H NMR (400 MHz, CDCl3): δ 8.30 (d, J = 8.8
Hz, 2H), 8.04 (d, J = 8.8 Hz, 2H), 7.49–7.48 (m, 2H),
7.39–7.32 (m, 6H), 7.23–7.21 (m, 2H), 5.98 (s, 1H), 5.83 (s,
1H), 5.08 (s, 2H), 5.01 (d, J = 12.0 Hz, 1H), 3.00-2.94 (m,
1H), 1.37-1.29 (m, 2H), 0.78 (t, J = 7.2 Hz, 3H) ppm; 13C
NMR (50 MHz, CDCl3): δ 172.8, 134.7, 133.6, 132.9, 129.1,
128.9, 128.8, 128.6, 128.6, 128.1, 124.1, 124.0, 117.6, 71.5,
53.1, 48.7, 23.9, 10.8 ppm; ESI-HRMS: calcd for
C27H25N3O5S+Na 526.1413, found 526.1424.
20
Compound 3l, diastereomer 2. 34% yield; [α]D
=
20
Compound 3i. 93% yield; 68:32 dr; [α]D = −69.1 (c =
+17.6 (c = 0.25 in CHCl3); 81% ee, determined by HPLC
analysis [Daicel chiralpak AD, n-hexane/i-PrOH = 80/20,
1.0 mL/min, λ = 254 nm, t(major) = 15.29 min, t(minor) =
12.36 min]; 1H NMR (400 MHz, CDCl3): δ 8.31 (d, J = 8.8
Hz, 2H), 8.02 (d, J = 8.8 Hz, 2H), 7.46–7.44 (m, 2H),
7.40–7.30 (m, 6H), 7.26–7.20 (m, 2H), 5.70 (s, 1H), 5.47 (s,
1H), 5.20 (d, J = 12.0 Hz, 1H), 5.09 (d, J = 12.0 Hz, 1H),
4.97(d, J = 12.0 Hz, 1H), 2.94 (dt, J = 7.2, 2.8 Hz, 1H),
1.72–1.64 (m, 1H), 1.58-1.46 (m, 1H), 0.89 (t, J = 7.2 Hz,
3H) ppm; 13C NMR (100 MHz, CDCl3): δ 173.4, 134.5,
133.8, 133.7, 129.4, 129.3, 129.1, 129.0, 128.9, 128.8,
128.5, 128.4, 128.1, 124.1, 122.8, 116.5, 71.3, 53.7, 50.6,
24.9, 11.7 ppm; ESI-HRMS: calcd for C27H25N3O5S+Na
526.1413, found 526.1385.
0.75 in CHCl3); 92% ee, determined by HPLC analysis
[Daicel chiralpak AD, n-hexane/i-PrOH = 90/10, 1.0 mL/min,
λ = 254 nm, t(major) = 13.55 min, t(minor) = 23.85 min];
1H NMR (400 MHz, CDCl3): δ 7.55–7.53 (m, 2H), 7.49 (d,
J = 4.8 Hz, 2H), 7.34–7.15 (m, 6H), 7.14–7.09 (m ,2H),
7.05–7.01 (m, 1H), 6.86–6.84 (m, 2H), 6.73–6.71 (m, 1H),
6.60 (s, 1H), 6.46 (s, 1H), 5.52 (d, J = 12.0 Hz, 1H), 5.23 (d,
J = 12.0 Hz, 1H), 3.75 (s, 3H), 2.33 (s, 3H) ppm; 13C NMR
(50 MHz, CDCl3): δ 171.7, 166.6, 151.5, 143.2, 142.4,
141.8, 138.4, 135.5, 129.4, 129.4, 129.1, 129.0, 128.8,
128.7, 128.2, 126.5, 126.4, 126.3, 124.6, 121.0, 54.5, 52.3,
44.7, 21.4 ppm; ESI-HRMS: calcd for C30H27NO5S2+Na
568.1228, found 568.1219.
20
Compound 3m. 97% yield; 85:15 dr; [α]D20 = −164.3 (c =
0.46 in CHCl3); 91% ee, determined by HPLC analysis
[Daicel chiralpak AS, n-hexane/i-PrOH=80/20, 1.0 mL/min,
Compound 3j. 99% yield; 84:16 dr; [α]D = −65.0 (c =
1.00 in CHCl3); 99% ee, determined by HPLC analysis
[Daicel chiralpak AD, n-hexane/i-PrOH = 80/20, 1.0 mL/min,
λ = 254 nm, t(major) = 8.28 min, t(minor) = 13.32 min]; 1H
NMR (400 MHz, CDCl3): δ 7.52–7.46 (m, 4H), 7.31–7.26
(m, 2H), 7.21–7.17 (m, 4H), 7.13–7.03 (m, 7H), 6.84 (d, J =
8.0 Hz, 2H), 6.72 (s, 1H), 6.42 (s, 1H), 5.54 (d, J = 12.0 Hz,
1H), 5.13 (d, J = 12.0 Hz, 1H), 2.35 (s, 3H), 2.34 (s, 3H)
ppm; 13C NMR (50 MHz, CDCl3): δ 198.1, 172.3, 151.5,
149.9, 143.1, 138.9, 135.5, 129.3, 129.3, 129.1, 128.6,
128.5, 128.1, 127.8, 127.7, 126.7, 126.3, 126.2, 125.6,
121.0, 53.5, 47.4, 25.9, 21.4 ppm; ESI-HRMS: calcd for
C32H29NO4S+H 524.1896, found 524.1897.
1
λ = 254 nm, t(major) = 9.09 min, t(minor) =14.91 min]; H
NMR (400 MHz, CDCl3): δ 8.24 (d, J = 8.0 Hz, 2H), 8.30
(d, J = 8.0 Hz, 2H), 7.36–7.28 (m, 3H), 7.26–7.21 (m, 4H),
7.14–7.13 (m, 3H), 7.10–7.05 (m, 3H), 7.02–7.00 (m, 2H),
6.41 (s, 1H), 6.32 (s, 1H), 5.36 (d, J = 12.0 Hz, 1H), 5.19 (d,
J = 12.0 Hz, 1H), 5.08 (d, J = 12.0 Hz, 1H), 4.74 (d, J =
12.0 Hz, 1H), 3.63 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3): δ 174.2, 166.4, 149.8, 146.9, 141.7, 138.1, 135.0,
133.6, 129.1, 128.8, 128.5, 128.5, 128.4, 128.1, 127.9,
127.8, 127.6, 126.8, 124.8, 123.9, 71.3, 54.4, 52.0, 49.4
ppm; ESI-HRMS: calcd for C32H28N2O7S+Na 607.1515,
found 607.1512.
Compound 3n. 72% yield; [α]D = −131.9 (c = 0.70 in
CHCl3); 88% ee, determined by HPLC analysis [Daicel
chiralpak AD, n-hexane/i-PrOH = 80/20, 1.0 mL/min, λ =
254 nm, t(major) = 9.79 min, t(minor) =13.75 min]; H
NMR (400 MHz, CDCl3): δ 7.76 (d, J = 8.0 Hz, 2H),
7.30–7.19 (m, 10H), 7.05–7.03 (m, 2H), 6.32 (s, 1H), 5.74
(s, 1H), 4.96 (s, 2H), 4.58 (t, J = 8.0 Hz, 1H), 3.64 (s, 3H),
3.62–3.58 (m, 1H), 3.51–3.45 (m, 1H), 2.44 (s, 3H) ppm;
13C NMR (50 MHz, CDCl3): δ 171.7, 141.8, 140.5, 131.0,
129.4, 128.6, 128.4, 127.9, 127.6, 126.9, 125.5, 118.9,
Compound 3k. 88% yield; 87:13 dr; [α]D20 = +45.3 (c =
0.86 in CHCl3); 73% ee, determined by HPLC analysis
[Daicel chiralpak AD, n-hexane/i-PrOH = 80/20, 1.0 mL/min,
λ = 254 nm, t(major) = 13.67 min, t(minor) = 8.45 min]; 1H
NMR (400 MHz, CDCl3): δ 7.54 (d, J = 8.0 Hz, 2H),
7.43–7.32 (m, 5H), 7.26–7.10 (m, 11H), 6.95 (d, J = 8.0 Hz,
2H), 6.51 (s, 1H), 6.17 (s, 1H), 5.52 (br s, 1H), 4.48 (d, J =
12.0 Hz, 1H), 2.35 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3): δ 170.9, 151.3, 143.4, 138.0, 136.0, 134.3, 131.4,
130.8, 129.5, 129.2, 128.7, 128.4, 128.2, 127.9, 127.6,
126.9, 126.5, 125.0, 121.1, 118.3, 53.2, 52.3, 21.5 ppm;
ESI-HRMS: calcd for C31H26N2O3S+H 507.1742, found
20
1

84
Peng J, et al. Sci China Chem January (2011) Vol.54 No.1
108.9, 70.3, 51.9, 42.5, 38.2, 21.5 ppm; ESI-HRMS: calcd
(Table 1, entry 1). Slightly lower enantioselectivities were
obtained for the catalysis of (DHQD)2PHAL and
(DHQD)2PYR (entries 2 and 3), but the diastereoselectivi-
ties were better. A poor ee value was obtained in the pres-
ence of (DHQ)2AQN, while the product possesses the op-
posite configuration (entry 4). Subsequently, we further
investigated the effects of solvents by the catalysis of
(DHQD)2AQN. Pleasingly, a higher ee value could be ob-
tained in toluene and PhCF3 (entries 5 and 6), and the reac-
tion was slightly accelerated simultaneously. Longer reac-
tion time was required at lower temperature, although the ee
value was slightly improved (entry 7). Fortunately, better
enantio- and diastereoselectivity were afforded when benzyl
or phenyl esters were used (entries 8 and 9).
Having established the optimal reaction conditions, we
next investigated the scope of this reaction (Table 2). Ex-
cellent ee values and good dr ratios were obtained for MBH
carbonates bearing electron-withdrawing or -donating aryl
groups (entries 2–5). In addition, heteroaryl-substituted
MBH carbonates could be successfully applied, and excel-
lent enantioselectivities were attained albeit with lower dr
ratios (entries 6 and 7). Good results were also obtained
with the MBH adduct from methyl vinyl ketone (entry 8).
Besides, modest ee value and dr ratio were obtained for the
MBH adduct from acrylonitrile (entry 9). It was noteworthy
that the alkyl MBH adduct from acrylonitrile could be util-
ized in the AAA reaction though moderate ee value and
poor diastereoselectivity were observed, while the two di-
astereomers could be separated (entry 10). p-Nitrophenyl-
sulfonylimidate 1d exhibited good reactivity with MBH
carbonate 2a and an excellent ee value with a good dr ratio
were obtained (entry 11). Some substitutions at the α-posi-
for C27H27NO5S+Na 500.1508, found 500.1517.
20
Compound 3o, diastereomer 1. 33% yield; [α]D
=
−16.8 (c = 0.25 in CHCl3); 93% ee, determined by HPLC
analysis [Daicel Chiralcel OD, n-hexane/i-PrOH = 80/20,
1.0 mL/min, λ = 254 nm, t(major) = 6.30 min, t(minor) =
1
5.35 min]; H NMR (400 MHz, CDCl3): δ 8.25 (d, J = 8.8
Hz, 2H), 7.82 (d, J = 8.8 Hz, 2H), 7.39–7.13 (m, 5H), 6.45
(s, 1H), 5.99 (s, 1H), 4.54 (dt, J = 6.8, 3.2 Hz, 1H), 4.23 (d,
J = 12.0 Hz, 1H), 4.02–3.94 (m, 1H), 3.80–3.75 (m, 1H),
3.71 (s, 3H), 1.85–1.73 (m, 1H), 1.71–1.64 (m, 1H),
1.47–1.37 (m, 2H), 1.33–1.30 (m, 2H), 1.10 (t, J = 7.2 Hz,
3H), 0.90 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (50 MHz,
CDCl3): δ 177.4, 166.1, 147.8, 142.4, 139.8, 128.7, 128.5,
127.9, 127.2, 126.6, 125.1, 124.1, 65.0, 52.0, 48.1, 47.6,
31.8, 28.4, 22.6, 13.7, 13.4 ppm; ESI-HRMS: calcd for
C25H30N2O7S+Na 525.1671, found 525.1732.
20
Compound 3o, diastereomer 2. 33% yield; [α]D
=
–65.7 (c = 0.30 in CHCl3); 93% ee, determined by HPLC
analysis [Daicel Chiralcel OD, n-hexane/i-PrOH = 80/20,
1.0 mL/min, λ = 254 nm, t(major) = 5.88 min, t(minor) =
1
6.71 min]; H NMR (400 MHz, CDCl3): δ 8.37 (d, J = 8.8
Hz, 2H), 8.14 (d, J = 8.8 Hz, 2H), 7.39–7.24 (m, 5H), 6.31
(s, 1H), 6.26 (s, 1H), 4.34 (d, J = 12.0 Hz, 1H), 4.30–4.24
(m, 1H), 4.11 (q, J = 6.8 Hz, 2H), 3.68 (s, 3H), 1.51–1.42
(m, 1H), 1.15–1.10 (m, 1H), 1.25–1.19 (m, 7H), 0.76 (t, J =
6.8 Hz, 3H) ppm; 13C NMR (50 MHz, CDCl3): δ 177.4,
166.8, 147.7, 142.3, 139.7, 128.7, 128.5, 127.9, 127.2,
126.5, 125.1, 124.1, 65.0, 52.0, 48.0, 47.6, 31.7, 28.4, 22.6,
13.7, 13.4 ppm; ESI-HRMS: calcd for C25H30N2O7S+Na
525.1671, found 525.1662.
Compound 3p. 58% yield; 85:15 dr; [α]D20 = −64.5 (c =
0.55 in CHCl3); 96% ee, determined by HPLC analysis
[Daicel chiralpak AD, n-hexane/i-PrOH=80/20, 1.0 mL/min,
Table 1 Screening studies of organocatalytic AAA reaction of sulfon-
ylimidate 1 and MBH carbonate 2aa)
1
λ = 254 nm, t(major) = 6.99 min, t(minor) = 8.19 min]; H
NMR (400 MHz, CDCl3): δ 8.37 (d, J = 7.2 Hz, 2H), 8.15
(d, J = 7.2 Hz, 2H), 7.37–7.28 (m, 5H), 6.49 (s, 1H), 6.20 (s,
1H), 4.52 (d, J = 12.0 Hz, 1H), 4.30–4.24 (m, 1H),
4.12–4.04 (m, 2H), 2.24 (s, 3H), 1.62–1.46 (m, 2H),
1.24–1.09 (m, 7H), 0.76 (t, J = 7.2 Hz, 3H) ppm; 13C NMR
(50 MHz, CDCl3): δ 197.9, 177.6, 150.3, 147.8, 140.1,
128.6, 128.4, 127.8, 127.4, 127.0, 125.7, 124.1, 64.9, 48.0,
45.3, 31.8, 28.5, 25.7, 22.6, 13.7, 13.5 ppm; ESI-HRMS:
calcd for C25H30N2O6S+Na 509.1722, found 509.1723
Y b) ee c)
Entry
Cat.
Sol
1
t (h)
dr d)
(%)
89
85
90
98
92
94
97
92
98
(%)
84
:
1
2
3
4
5
6
7 e
8
9
(DHQD)2AQN
(DHQD)2PHAL
(DHQD)2PYR
(DHQ)2AQN
DCE
DCE
DCE
DCE
Tol
1a
1a
1a
1a
1a
1a
1a
1b
1c
32
42
32
22
21
21
55
24
36
73 27
:
79
90 10
:
73
85 15
:
−30
90
81 19
3 Results and discussion
:
(DHQD)2AQN
(DHQD)2AQN
(DHQD)2AQN
(DHQD)2AQN
(DHQD)2AQN
73 27
:
PhCF3
Tol
89
72 28
:
91
73 27
In the initial study, a range of commercially available modi-
fied cinchona alkaloids were screened in the AAA reaction
of sulfonylimidate 1a and MBH carbonate 2a at 50 °C in
DCE. To our gratification, the desired allylic product 3a
was isolated with good enantioselectivity and yield although
with a moderate dr ratio by the catalysis of (DHQD)2AQN
:
Tol
92
83 17
:
Tol
96
87 13
a) Unless noted otherwise, reactions were performed with 0.05 mmol 1,
0.1mmol 2a and 10 mol% catalyst in 0.5 mL solvent at 50 °C. b) Com-
bined isolated yield of diastereomers. c) Determined by chiral HPLC
analysis. d) Determined by 1H NMR. e) At 35 °C.

Peng J, et al. Sci China Chem January (2011) Vol.54 No.1
85
tion of sulfonylimidates were also tested. Allylation of sim-
4 Conclusions
ple sulfonylimidate 1e was achieved in good yield with a
high ee (entry 12). For sulfonylimidate 1f bearing longer
carbon chain, stronger electron-withdrawing N-sulfonyl
group was needed, and moderate yields and excellent enan-
tioselectivities were observed (entries 13 and 14).
In conclusion, we have developed an organocatalytic asym-
metric allylic alkylation of sulfonylimidates with Morita-
Baylis-Hillman carbonates by the catalysis of commercially
available modified cinchona alkaloids. Good stereoselectiv-
ities were generally achieved for a broad spectrum of sub-
strates (dr up to 89:11, up to 99% ee). Currently further
studies are underway to expand the synthetic utility of this
reaction.
This work was financially Supported by the National Natural Science
Foundation of China (20772084).
1
2
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Figure 1 X-ray structure of enantiopure 3c.
3
4
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carbonates 2 a)
5
6
7
8
9
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Yield b)
(%)
COOMe 3c, 98
COOMe 3d, 98
Ee c)
(%)
Entry
1
R4
EWG
Dr d)
1
2
1c
1c
1c
1c
1c
1c
1c
1c
1c
1d
1d
1e
1f
Ph
96e
95
:
87 13
:
p-ClC6H4
87 13
:
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and reaction of carbanions from ester or amide equivalents using
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adducts. J Am Chem Soc, 2000, 122: 3534–3535
13 Rajesh S, Banerji B, Iqbal J. Palladium(0)-catalyzed regioselective
synthesis of α-dehydro-β-amino esters from amines and allyl acetates.
J Org Chem, 2002, 67: 7852–7857
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3
m-MeC6H4 COOMe 3e, 82
p-MeOC6H4 COOMe 3f, 86
97
87 13
:
4
98
86 14
:
5
o-BrC6H4
2-furyl
2-thienyl
Ph
COOMe 3g, 94
COOMe 3h, 99
COOMe 3i, 93
COMe 3j, 99
93
89 11
:
6
90
67 33
:
7
92
68 32
:
8
99
84 16
:
9
Ph
CN
CN
3k, 88
3l, 68
73
87 13
f)
:
10
11
12
13
14
Me
81/81
91
50 50
:
Ph
COOMe 3m, 97
COOMe 3n, 72
COOMe 3o, 66
COMe 3p, 58 g)
85 15
Ph
88
–
f)
:
Ph
93/93
96
50 50
:
1f
Ph
85 15
a) Unless noted otherwise, reactions were performed with 0.1 mmol 1,
0.2 mmol 2 and 10 mol% (DHQD)2AQN in 1.0 mL toluene at 50 °C. b)
Combined isolated yield of diastereomers. c) Determined by chiral HPLC
1
analysis. d) Determined by H NMR or HPLC analysis. e) The absolute
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Morita-Baylis-Hillman products. Tetrahedron Lett, 2004, 45: 4967–
4971
configuration of major 3c was determined by X-ray analysis, see Figure 1.
The other major diastereomers were assigned accordingly. f) Calculated
from the isolated yields of isomers. g) Isolated yield of the major di-
astereomer.

86
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