K
E. R. T. Robinson et al.
Paper
Synthesis
1H NMR (400 MHz, CDCl3): δ = 1.79 (dd, J = 7.0, 1.7 Hz, 3 H,
CH=CHCH3), 2.06 (s, 3 H, COCH3), 3.01 (dd, J = 7.3, 1.4 Hz, 2 H, CH2),
5.18 (d, J = 1.4 Hz, 4 H, 2 × CO2CH2Ph), 5.95 (dt, J = 16.0, 1.4 Hz, 1 H,
CH=CHCOCH3), 6.29 (dq, J = 15.2, 1.7 Hz, 1 H, CH=CHCH3), 6.67 (dt, J =
16.0, 7.3 Hz, 1 H, CH=CHCOCH3), 6.98 (dq, J = 15.2, 7.0 Hz, 1 H,
CH=CHCH3), 7.19–7.30 (m, 4 H, Ph), 7.30–7.35 (m, 6 H, Ph).
13C{1H} NMR (100 MHz, CDCl3): δ = 18.4 (CH=CHCH3), 26.5 (COCH3),
35.1 (CH2), 68.2 (2 × CO2CH2Ph), 69.6 (C(CO2Bn)2), 127.7 (CH=CHCH3),
128.6 (4 × Ph), 128.8 (4 × Ph), 128.8 (2 × Ph), 134.7 (2 × i-Ph), 134.8
(CH=CHCOCH3), 142.1 (CH=CHCOCH3), 145.6 (CH=CHCH3), 166.8
(2 × CO2Bn), 188.5 (COCH=CH), 198.4 (COCH3).
HRMS (NSI+): m/z [M + H]+ calcd for C14H19O6+: 283.1176; found:
283.1177.
Dimethyl 1-Oxo-3,7-diphenyl-4a,5,7,7a-tetrahydrocyclopen-
ta[c]pyran-6,6(1H)-dicarboxylate (2g)
By following General Procedure D, dimethyl (E)-2-(4-oxo-4-phenyl-
but-2-en-1-yl)malonate (70 mg, 0.25 mmol), LiHMDS (1 M in THF,
0.28 mL, 0.28 mmol), HyperBTM 4 (16 mg, 0.05 mmol), iPr2NEt (62 μL,
0.35 mmol) and cinnamoyl chloride (59 mg, 0.35 mmol) were reacted
in THF (5.35 mL) to give 2g in 84:16 dr. The mixture was purified by
chromatography on silica gel (EtOAc/hexane, 1:5) to afford 2g (64.7
mg, 64%) as a yellow oil in 95:5 dr.
MS (NSI+): m/z (%) = 457 (100) [M + Na]+.
HRMS (NSI+): m/z [M + Na]+ calcd for C26H26NaO6+: 457.1622; found:
20
[α]D –17.0 (c 1.1 in CHCl3); chiral HPLC analysis (ChiralPak IA; i-
PrOH/hexane, 2%; flow rate 1 mL min–1; 211 nm; 30 °C): tR = 23.5
(4aS,7S,7aR), 32.9 (4aR,7R,7aS) min; 82.0:18.0 er.
457.1610.
IR (film): 2951 (C-H), 2849 (C-H), 1759 (C=O), 1748 (C=O), 1724
Dimethyl (4aS,7S,7aR)-3,7-Dimethyl-1-oxo-4a,5,7,7a-tetrahydro-
cyclopenta[c]pyran-6,6(1H)-dicarboxylate (2f) and Dimethyl 2-
[(E)-But-2-enoyl]-2-[(E)-4-oxopent-2-en-1-yl]malonate (3f)
(C=O) cm–1
.
1H NMR (500 MHz, CDCl3): δ = 2.30 (dd, J = 14.0, 4.4 Hz, 1 H, C(5)HA),
3.18–3.12 (m, 4 H, CO2CH3, C(5)HB), 3.60–3.55 (m, 1 H, C(7a)H), 3.65–
3.60 (m, 1 H, C(4a)H), 3.74 (s, 3 H, CO2CH3), 4.73 (d, J = 8.9 Hz, 1 H,
C(7)H), 5.60 (d, J = 2.5 Hz, 1 H, C(4)H), 7.30–7.25 (m, 1 H, Ph), 7.35–
7.30 (m, 4 H, 4 × Ph), 7.43–7.37 (m, 3 H, 3 × Ph), 7.66–7.60 (m, 2 H,
2 × Ph).
13C{1H} NMR (125 MHz, CDCl3): δ = 36.7 (C(4a)H), 41.2 (C(5)H2), 47.6
(C(7a)H), 52.3 (CO2CH3), 53.1 (CO2CH3), 53.6 (C(7)H), 65.0 (C(6)), 102.2
(C(4)H), 124.8 (2 × Ph), 127.8 (p-Ph), 128.3 (2 × Ph), 128.6 (2 × Ph),
128.7 (2 × Ph), 129.2 (p-Ph), 132.1 (i-Ph), 137.3 (i-Ph), 149.2 (C(3)),
168.4 (C(1)), 170.2 (CO2CH3), 171.6 (CO2CH3).
By following General Procedure D, dimethyl (E)-2-(4-oxopent-2-en-1-
yl)malonate (107 mg, 0.5 mmol), LiHMDS (1 M in THF, 0.55 mL, 0.55
i
mmol), HyperBTM 4 (30.8 mg, 0.10 mmol), Pr2NEt (0.12 mL, 0.7
mmol) and crotonoyl chloride (67 μL, 0.7 mmol) were reacted in THF
(10 mL) to give a 73:27 mixture of 2f and 3f. The mixture was purified
by chromatography on silica gel (EtOAc/hexane, 20→30%) to afford 2f
(79 mg, 56%) as a pale-yellow oil and 3f (28 mg, 20%) as a pale-yellow
oil.
Compound 2f
[α]D20 +117.4 (c 0.98 in CH2Cl2); chiral HPLC analysis (ChiralPak AS-H;
i-PrOH/hexane, 2.5%; flow rate 1 mL min–1; 211 nm; 30 °C): tR = 9.3
(4aS,7S,7aR), 15.8 (4aR,7R,7aS) min; 93.5:6.5 er.
Selected data for minor diastereomer: 1H NMR (500 MHz, CDCl3): δ =
4.54 (d, J 11.8 Hz, 1 H, C(7)H), 6.12 (d, J = 2.1 Hz, 1 H, C(4)H).
IR (film): 2955 (C-H), 1726 (C=O) cm–1
.
Dimethyl 7-(4'-Methoxyphenyl)-1-oxo-3-phenyl-4a,5,7,7a tetra-
1H NMR (300 MHz, CDCl3): δ = 1.14 (d, J = 6.9 Hz, 3 H, C(7)CH3), 1.81
(dd, J = 2.3, 1.1 Hz, 3 H, C(3)CH3), 2.00 (dd, J = 14.0, 4.3 Hz, 1 H,
C(5)CHA), 2.71 (ddd, J = 11.2, 8.7, 0.8 Hz, 1 H, C(7)H), 2.77 (dd, J = 14.0,
8.2 Hz, 1 H, C(5)HB), 2.90–3.08 (m, 1 H, C(7a)H), 3.06–3.17 (m, 1 H,
C(4a)H), 3.71 (d, J = 3.0 Hz, 6 H, 2 × CO2CH3), 4.65 (dquin, J = 2.3,
1.2 Hz, 1 H, C(4)H).
13C{1H} NMR (75 MHz, CDCl3): δ = 15.2 (C(7)CH3), 18.8 (C(3)CH3), 34.8
(C(4a)H), 41.1 (C(5)H2), 44.1 (C(7)H), 48.2 (C(7a)H), 52.6 (CO2CH3),
52.8 (CO2CH3), 62.2 (C(6)), 103.2 (C(4)H), 147.0 (C(3)), 169.6 (C(1)),
171.2 (CO2CH3), 171.7 (CO2CH3).
hydrocyclopenta[c]pyran-6,6(1H)-dicarboxylate (2h)
By following General Procedure D, dimethyl (E)-2-(4-oxo-4-phenyl-
but-2-en-1-yl)malonate (70 mg, 0.25 mmol), LiHMDS (1 M in THF,
0.28 mL, 0.28 mmol), HyperBTM 4 (16 mg, 0.05 mmol), iPr2NEt (62 μL,
0.35 mmol) and 4-methoxycinnamoyl chloride (70 mg, 0.35 mmol)
were reacted in THF (5.4 mL) to give 2h in 92:8 crude dr. The mixture
was purified by chromatography on silica gel (toluene/CH2Cl2,
1:5→CH2Cl2) to afford 2h (40 mg, 37%) as a yellow oil in 95:5 dr.
20
[α]D −21.7 (c 1.0 in CHCl3); chiral HPLC analysis (ChiralPak AS-H;
i-PrOH/hexane, 5%; flow rate 1 mL min–1; 211 nm; 30 °C): tR = 32.2
(4aS,7S,7aR), 48.2 (4aR,7R,7aS) min; 72.0:28.0 er.
MS (NSI+): m/z (%) = 283 (100) [M + H]+.
IR (film): 2951 (C-H), 2839 (C-H), 1724 (C=O), 1748 (C=O), 1610
HRMS (NSI+): m/z [M + H]+ calcd for C14H19O6+: 283.1176; found:
283.1177.
(C=C), 1250 (C-O) cm–1
.
1H NMR (500 MHz, CDCl3): δ = 2.30 (dd, J = 14.0, 3.9 Hz, 1 H, C(5)HA),
3.16–3.13 (m, 1 H, C(5)HB), 3.23 (s, 3 H, CO2CH3), 3.57–3.52 (m, 1 H,
C(7a)H), 3.62–3.56 (m, 1 H, C(4a)H), 3.73 (s, 3 H, CO2CH3), 3.80 (s, 3 H,
OCH3), 4.63 (d, J = 9.6 Hz, 1 H, C(7)H), 5.57 (d, J = 3.2 Hz, 1 H, C(4)H),
6.88–6.83 (m, 2 H, 2 × Ar), 7.30–7.25 (m, 2 H, 2 × Ar), 7.43–7.36 (m,
3 H, 3 × Ph), 7.64–7.60 (m, 2 H, 2 × Ph).
13C{1H} NMR (125 MHz, CDCl3): δ = 36.4 (C(4a)H), 41.1 (C(5)H2), 47.6
(C(7a)H), 52.5 (CO2CH3), 53.0, 53.1 (C(7)H, CO2CH3), 55.2 (OCH3), 64.8
(C(6)), 102.4 (C(4)H), 113.6 (2 × Ar), 124.8 (2 × Ar), 128.5 (2 × Ar),
128.9 (Ar), 129.2 (Ar), 129.9 (2 × Ar), 132.2 (C(1′)H), 149.0 (C(3)),
159.0 (C(4′)OMe), 168.4 (C(1)), 170.4 (CO2CH3), 171.7 (CO2CH3).
Compound 3f
IR (film): 2957 (C-H), 1732 (C=O), 1676 (C=O) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.92 (dd, J = 7.0, 1.7 Hz, 3 H,
CH=CHCH3), 2.21 (s, 3 H, COCH3), 3.00 (dd, J = 7.4, 1.4 Hz, 2 H, CH2),
3.78 (s, 6 H, 2 × CO2CH3), 6.05 (dt, J = 16.0, 1.4 Hz, 1 H, CH=CHCOCH3),
6.39 (dq, J = 15.1, 1.6 Hz, 1 H, CH=CHCH3), 6.77 (dt, J = 16.0, 7.3 Hz,
1 H, CH=CHCOCH3), 7.05 (dq, J = 15.2, 7.0 Hz, 1 H, CH=CHCH3).
13C{1H} NMR (75 MHz, CDCl3): δ = 18.6 (CH=CHCH3), 26.7 (COCH3),
35.2 (CH2), 53.4 (2 × CO2CH3), 69.7 (C(CO2CH3)2), 127.4 (CH=CHCH3),
134.7 (CH=CHCOCH3), 142.2 (CH=CHCOCH3), 145.9 (CH=CHCH3),
167.5 (2 × CO2CH3), 188.7 (COCH=CH), 198.5 (COCH3).
MS (ESI+): m/z (%) = 459 (100) [M + Na]+.
HRMS: m/z [M + Na]+ calcd for C25H24NaO7+: 459.14; found: 459.1401.
MS (NSI+): m/z (%) = 283 (100) [M + H]+.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 27, A–O