Organocatalytic Enantioselective Addition
FULL PAPER
3H, COOCH2CH3), 1.17 (t, 3J
(s, 3H, COCH3), 2.77–2.86 (m, 2H, CHCH2), 3.60 (d, 3J
1H, CH(COOEt)2), 3.74 (s, 3H, OCH3), 3.77 (s, 3H, OCH3), 3.80–3.90
(m, 3H, COOCH2CH3, CHCH2), 4.03–4.16 (m, 2H, COOCH2CH3), 6.66–
6.70 ppm (m, 3H, CHarom.); 13C NMR (100 MHz, CDCl3): d=13.78, 13.95
(2COOCH2CH3), 30.28 (COCH3), 40.09 (CHCH2), 47.47 (CH2), 55.69,
N
4.17–4.30 (m, 3H, COOCH2CH3, CHCH2), 6.29 (s, 1H, CH=), 7.05–7.08
(m, 1H, CHarom.), 7.16–7.20 (m, 1H, CHarom.), 7.29–7.31 (m, 1H, CHarom.),
7.51–7.53 ppm (m, 1H, CHarom.); 13C NMR (100 MHz, CDCl3): d=13.76,
14.03 (2COOCH2CH3), 29.70 (COCH3), 30.44 (CHCH2), 31.25 (NCH3),
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47.79 (CH2), 57.23 (CH(COOEt)2), 61.50, 61.76 (2COOCH2CH3), 98.35
A
(CH=), 109.38, 119.31, 120.02, 121,12 (4CHarom.), 127.67, 136.98, 141.10
(3Cq), 167.57, 167.96 (2CO, ester), 205.64 ppm (CO); HRMS-ESI:
m/z: calcd for C20H25N1O5Na: 382.1630; found: 382.1645 [M+Na]+; the
ee was determined by SFC analysis by using a Chiralpak AD-H column
55.76 (2OCH3), 57.45 (CH(COOEt)2), 61.22, 61.53 (2COOCH2CH3),
N
110.92, 111.55, 119.92 (3CHarom.), 132.86, 147.90, 148.56 (3Cq), 167.61,
168.13 (2CO, ester), 206.17 (CO); HRMS-ESI: m/z: calcd for
C19H26O7Na: 389.1576; found: 389.1572 [M+Na]+; the ee was determined
by SFC analysis by using a Chiralpak AD-H column (10% iPrOH); flow
rate=1.0 mLminÀ1; tmajor =14.3, tminor =10.1 min (84% ee).
(10% iPrOH); flow rate=1.0 mLminÀ1
(84% ee).
; tmajor =14.3, tminor =13.4 min
Diethyl 2-((S)-3-oxo-1-(quinolin-3-yl)butyl)malonate (30): The title com-
pound was obtained according to the general procedure. Colourless oil;
Yield: 83%; Rf =0.46 (PE/Et2O 2:1); [a]2D0 =+25.0 (c=0.25 in chloro-
Diethyl 2-((S)-3-oxo-1,3-diphenylpropyl)malonate (26): The title com-
pound was obtained according to the general procedure (reaction time 5
days). White solid; Yield: 86%; Rf =0.42 (PE/Et2O 2:1); m.p. 548C; [a]D20
=+ 10.0 (c=0.25 in chloroform); 1H NMR (400 MHz, CDCl3): d=1.00
form); 1H NMR (400 MHz, CDCl3): d=0.92 (t, 3J
ACHTREUNG
COOCH2CH3), 1.19 (t, 3J
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(t, 3J
COOCH2CH3), 3.42–3.57 (m, 2H, CHCH2), 3.82 (d, 3J
1H, CH(COOEt)2), 3.92–3.97 (m, 2H, COOCH2CH3), 4.13–4.25 (m, 3H,
A
N
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E
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N
COOCH2CH3, CHCH2), 7.44–7.48 (m, 1H, CHarom.), 7.59–7.63 (m, 1H,
CHarom.), 7.70–7.72 (m, 1H, CHarom.), 7.99–8.01 (m, 2H, CHarom.), 8.82–
8.84 ppm (m, 1H, CHarom.); 13C NMR (100 MHz, CDCl3): d=13.68, 13.94
(2COOCH2CH3), 30.19 (COCH3), 37.76 (CHCH2), 46.83 (CH2), 56.69
COOCH2CH3, CHCH2), 7.14–7.18 (m, 1H, CHarom.), 7.21–7.27 (m, 4H,
CHarom.), 7.39–7.43 (m, 2H, CHarom.), 7.50–7.54 (m, 1H, CHarom.), 7.88–
7.91 ppm (m, 1H, CHarom.); 13C NMR (100 MHz, CDCl3): d=14.17, 14.43
(2COOCH2CH3), 41.21 (CHCH2), 43.04 (CH2), 57.99 (CH
G
(CH(COOEt)2), 61.49, 61.76 (2COOCH2CH3), 126.72, 127.64, 129.11,
N
61.77, 62.08 (2COOCH2CH3), 127.55, 128.50, 128.64, 128.80, 128.96,
133.45 (10CHarom.), 137.18, 140.84 (2Cq), 168.16, 168.77 (2CO,
ester), 197.95 ppm (CO); HRMS-ESI: m/z: calcd for C22H24O5Na:
391.1521; found: 391.1519 [M+Na]+; the ee was determined by SFC anal-
ysis by using a Chiralpak AD-H column (10% iPrOH); flow rate=
1.0 mLminÀ1; tmajor =45.1, tminor =31.0 min (44% ee).
129.26 (4CHarom.), 133.59 (Cq), 134.84 (CHarom.), 147.31, 147.32 (2Cq),
151.22 (CHarom.), 167.35, 167.83 (2CO, ester), 205.14 ppm (CO);
HRMS-ESI: m/z: calcd for C20H24O5N1: 358.1654; found: 358.1653
[M+H]+; the ee was determined by SFC analysis by using a Chiralpak
AD-H column (40% iPrOH); flow rate=1.0 mLminÀ1
tminor =5.0 min (79% ee).
; tmajor =6.4,
Diethyl 2-((S)-3-oxo-1-(thiophen-2-yl)butyl)malonate (27): The title com-
pound was obtained according to the general procedure. Colourless oil;
Diethyl 2-((S)-1-(naphthalen-3-yl)-3-oxobutyl)malonate (31): The title
compound was obtained according to the general procedure. White solid;
Yield: 89%; Rf =0.31 (PE/Et2O 2:1); m.p. 468C; [a]2D0 =+15.3 (c=1 in
Yield: 81%; Rf =0.29 (PE/Et2O 2:1); [a]D20
=
+14.3 (c=1 in chloro-
(H,H)=7.1 Hz, 3H,
(H,H)=7.0 Hz, 3H, COOCH2CH3), 2.04 (s,
form); 1H NMR (400 MHz, CDCl3): d=1.08 (t, 3J
G
chloroform); 1H NMR (400 MHz, CDCl3): d=0.93 (t, 3J
ACHTREUNG
COOCH2CH3), 1.20 (t, 3J
A
3H, COOCH2CH3), 1.24 (t, 3J
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3
3
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3H, COCH3), 2.97 (d, J
A
(H,H)=
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9.5 Hz, 1H, CH
G
G
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(m, 2H, COOCH2CH3), 4.23–4.29 (m, 1H, CHCH2), 6.82–6.86 (m, 2H,
CHarom.), 7.09–7.11 ppm (m, 1H, CHarom.); 13C NMR (100 MHz, CDCl3):
d=13.82, 13.97 (2COOCH2CH3), 30.27 (COCH3), 35.61 (CHCH2),
4.13–4.23 (m, 3H, COOCH2CH3, CHCH2), 7.38–7.45 (m, 3H, CHarom.),
7.70–7.71 (m, 1H, CHarom.), 7.75–7.77 ppm (m, 3H, CHarom.); 13C NMR
(100 MHz, CDCl3): d=13.69, 14.00 (2COOCH2CH3), 30.28 (COCH3),
47.90 (CH2), 57.03 (CH
G
40.54 (CHCH2), 47.37 (CH2), 57.40 (CH(COOEt)2), 61.29, 61.62 (2
N
124.18, 125.72, 126.56 (3CHarom.), 143.51 (Cq), 167.51, 167.84 (2CO,
ester), 205.66 ppm (CO); HRMS-ESI: m/z: calcd for C15H20S1O5Na:
335.0929; found: 335.0924 [M+Na]+; the ee was determined by SFC anal-
ysis by using a Chiralpak AD-H column (10% iPrOH); flow rate=
1.0 mLminÀ1; tmajor =9.2, tminor =7.8 min (88% ee).
COOCH2CH3), 125.79, 126.06, 126.16, 127.08, 127.55, 127.79, 128.18 (7
CHarom.), 132.59, 133.29, 138.05 (3Cq), 167.62, 168.19 (2CO, ester),
205.89 ppm (CO); HRMS-ESI: m/z: calcd for C21H25O5: 357.1702; found:
357.1700 [M+H]+; the ee was determined by SFC analysis by using a
Chiralpak AD-H column (10% iPrOH); flow rate=1.0 mLminÀ1; tmajor
27.1, tminor =19.7 min (88% ee).
=
Diethyl 2-((S)-1-(furan-2-yl)-3-oxobutyl)malonate (28): The title com-
pound was obtained according to the general procedure. Pale-yellow oil;
Yield: 84%; Rf =0.29 (PE/Et2O 2:1); [a]2D0 =+10.1 (c=1 in chloroform);
Diethyl 2-((S)-1-(4-phenyl-phenyl)-3-oxobutyl)malonate (32): The title
compound was obtained according to the general procedure. White solid;
Yield: 88%; Rf =0.36 (PE/Et2O 2:1); m.p. 648C; [a]2D0 =+ 14.3 (c=1 in
1H NMR (400 MHz, CDCl3): d=1.13 (t, 3J
ACHTREUNG
COOCH2CH3), 1.20 (t, 3J
A
chloroform); 1H NMR (400 MHz, CDCl3): d=1.01 (t, 3J
ACHTREUNG
C
3H, COOCH2CH3), 1.25 (t, 3J
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A
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2H, COOCH2CH3), 6.05–6.07 (m, 1H, CHarom.), 6.20–6.22 (m, 1H,
CHarom.), 7.22–7.26 ppm (m, 1H, CHarom.); 13C NMR (100 MHz, CDCl3):
d=14.30, 14.37 (2COOCH2CH3), 30.45 (COCH3), 34.25 (CHCH2),
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(m, 2H, COOCH2CH3), 7.28–7.33 (m, 3H, CHarom.), 7.38–7.41 (m, 2H,
CHarom.), 7.48–7.57 ppm (m, 4H, CHarom.); 13C NMR (100 MHz, CDCl3):
d=13.75, 14.01 (2COOCH2CH3), 30.27 (COCH3), 40.12 (CHCH2),
44.89 (CH2), 55.35 (CH(COOEt)2), 61.91, 61.95 (2COOCH2CH3),
G
107.31, 110.64, 141.97 (3CHarom.), 153.85 (Cq), 168.08, 168.24 (2CO,
ester), 206.17 ppm (CO); HRMS-ESI: m/z: calcd for C15H20O6Na:
319.1158; found: 319.1156 [M+Na]+; the ee was determined by SFC anal-
ysis by using a Chiralpak AD-H column (10% iPrOH); flow rate=
1.0 mLminÀ1; tmajor =6.0, tminor =5.6 min (85% ee).
47.35 (CH2), 57.36 (CH(COOEt)2), 61.32, 61.62 (2COOCH2CH3),
A
126.93, 127.09, 127.24, 128.61, 128.73 (9CHarom.), 139.61, 139.97, 140.64
(3Cq), 167.67, 168.17 (2CO, ester), 205.94 ppm (CO); HRMS-ESI:
m/z: calcd for C23H26O5Na: 405.1678; found: 405.1666 [M+Na]+; the ee
was determined by SFC analysis by using a Chiralpak AD-H column
(10% iPrOH); flow rate=1.0 mLminÀ1
(85% ee).
; tmajor =46.9, tminor =25.9 min
Diethyl 2-((S)-1-(1-methyl-1H-indol-2-yl)-3-oxobutyl)malonate (29): The
title compound was obtained according to the general procedure. Yellow
oil; Yield: 91%; Rf =0.44 (PE/Et2O 2:1); [a]2D0 = À4.0 (c=1.1 in chloro-
Methyl 2-((R)-3-oxocyclohexyl)acetate (34a): The title compound was
obtained according to the general procedure. Pale-yellow oil; Yield:
92%; Rf =0.27 (PE/Et2O 2:1); [a]2D0 =+4.3 (c=1 in chloroform);
1H NMR (400 MHz, CDCl3): d=1.36–1.43 (m, 1H, CH2a), 1.59–1.71 (m,
1H, CH2b), 1.86–1.93 (m, 1H, CH2c), 1.97–2.10 (m, 2H, CH2), 2.17–2.43
form); 1H NMR (400 MHz, CDCl3): d=1.08 (t, 3J
(H,H)=7.1 Hz, 3H,
G
COOCH2CH3), 1.28 (t, 3J
3H, COCH3), 2.97–3.01 (m, 2H, CHCH2), 3.79 (d, 3J
CH(COOEt)2), 3.88 (s, 3H, NCH3), 3.92–4.05 (m, 2H, COOCH2CH3),
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Chem. Eur. J. 2008, 14, 6155 – 6165
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6163