2486
M. Pariollaud et al. / Tetrahedron Letters 55 (2014) 2484–2486
J = 8.3 Hz, 1H, H-50), 6.88 (d, J = 8.0 Hz, 1H, H-60), 6.20 (s, 1H, H-6), 5.21–5.03
(m, 8H), 4.89 (d, J = 7.3 Hz, 1H, H-2), 4.29,4.18 (AB, J = 11.9 Hz, 2H), 3.70 (m, 1H,
Supplementary data
H-3), 2.93 (dd, J = 16.5, 5.3 Hz, 1H, H-4b), 2.70 (dd, J = 16.5, 8.0 Hz, 1H, H-4a).
Supplementary data (copies of all 1H NMR, 13C NMR, and mul-
tidimensional NMR spectra) associated with this article can be
13C NMR (125 MHz, CDCl3): d 184.4, 160.5, 157.7, 154.3, 149.0, 138.0, 137.5,
137.4, 137.3, 136.3, 136.2, 131.5, 128.8–127.2, 120.2, 115.8, 115.0, 113.6,
105.7, 103.1, 91.1, 80.1, 74.1, 71.8, 71.5, 71.2, 71.1, 70.4, 25.7. IR (CDCl3, cmꢀ1):
3066, 3034, 2919, 2873, 1715, 1606. HRMS (ESI-TOF) m/z calcd for C52H43F3O7
[M+H]+ 837.3039, found: 837.3040. ½a 2D5
ꢁ
+3.7 (c 2.0, CDCl3).
3,5,7,30,40-Penta-O-benzyl-8-carboxycatechin (5): Compound
4
(950 mg,
1.1 mmol) was dissolved in DMF (7.5 ml) and water (0.020 ml) then stirred
at room temperature for 2 min. NaH (0.454 g, 11. mmol) was added and the
solution was heated to 60 °C for 1.5 h. The reaction mixture was then quenched
with 1 N HCl, extracted with EtOAc, washed with water, dried over Na2SO4, and
evaporated in vacuo. The residue was then chromatographed (EtOAc–hexane,
2:8 ? 6:4) to yield 655 mg (72%) of 5 as a light yellow oil. 1H NMR (500 MHz,
CDCl3): d 7.37–7.15 (m, 23H), 7.02–6.99 (m, 2H), 6.94 (s, 1H, H-20), 6.82 (s, 2H,
H-50, H-60), 6.14 (s, 1H, H-6), 5.08–4.94 (m, 8H), 4.89 (d, J = 7.3 Hz, 1H, H-2),
4.24,4.14 (AB, J = 11.9 Hz, 2H), 3.67 (m, 1H, H-3), 2.82 (dd, J = 16.6, 5.2 Hz, 1H,
References and notes
H-4b), 2.62 (dd, J = 16., 7.8 Hz, 1H, H-4a
). 13C NMR (125 MHz, CDCl3): d 165.1,
159.4, 158.3, 154.2, 149.0, 137.8, 137.3, 137.2, 136.3, 136.2, 131.3, 128.7–
127.1, 119.9, 115.0, 113.5, 103.3, 103.2, 92.3, 80.2, 73.6, 71.7, 71.6, 71.4, 71.1,
70.3, 25.4. IR (CDCl3, cmꢀ1): 3500–2800 (br s), 3064, 3033, 2931, 1730, 1695,
1606. HRMS (ESI-TOF) m/z calcd for
C
51H45O8 [M+H]+ 785.3114, found
785.3113. ½a 2D5
ꢁ
+5.4 (c 1.3, CDCl3).
Bis(3,5,7,30,40-Penta-O-benzyl-8-catechinyl)methanone (6): To
a solution of 5
(69.2 mg, 0.088 mmol) in anhydrous CH2Cl2 were added TFAA (14.71 ll,
0.106 mmol) and 3,5,7,30,40-Penta-O-benzylcatechin11 (65.3 mg, 0.088 mmol).
After three hours, the solution was poured into ice-H2O and was extracted
with CH2Cl2. The organic layers were washed with satd NaHCO3 and H2O, dried
over Na2SO4, and evaporated in vacuo. The residue was then chromatographed
(EtOAc–hexane, 1:9 ? 5:5) to yield 105 mg (77%) of 6. 1H NMR (500 MHz,
DMSO): d 7.48–7.13 (m, 46H), 6.95 (4H), 6.86 (2H), 6.70 (2H), 6.61 (2H), 6.44
(2H, H-6), 5.16 (2H), 5.10 (2H), 5.04 (2H), 4.88 (2H), 4.22 (2H, H-2), 3.95 (2H),
3.52 (2H, H-3), 2.90 (1H, H-4b), 2.40 (1H, H-4a
). 13C NMR (125 MHz, DMSO): d
13. (a) Selenski, C. General method for the construction of type-A
proanthocyanidins: Synthesis of racemic-diinsininone. Ph.D. Thesis,
University of California, Santa Barbara, California, 2006; p 217.; (b) Aurell, M.
14. Magdziak, D. Development and Application of New Oxidation Reactions for
Organic Synthesis. Ph.D. Thesis. University of California, Santa Barbara,
California, 2003; p 220.
16. Bis(8-catechinyl)methane (1): Palladium on carbon (93 mg, 0.087 mmol) was
189.5 (C-carbonyl), 157.6, 157.3, 153.1, 148.0, 138.3, 137.2, 137.0, 131.9,
128.5–127.2, 120.2, 114.9, 114.8, 110.0, 102.0, 91.3, 79.0, 74.2, 70.6, 70.2, 69.9,
69.8, 69.5, 26.2. IR (CDCl3, cmꢀ1): 3065, 3033, 2902, 1730, 1655, 1606. HRMS
(ESI-TOF) m/z calcd for C101H87O13 [M+H]+ 1507.6205, found 1507.6138. ½a 2D5
ꢁ
+18.3 (c 1.1, CDCl3).
Bis(3,5,7,30,40-Penta-O-benzyl-8-catechinyl)methane (9): A solution of 6 (326 mg,
0.216 mmol) in anhydrous THF (2162
ll) was cooled to ꢀ78 °C and LiAlH4
(16.4 mg, 0.432 mmol) was added. The mixture was stirred for 30 min while
slowly being warmed to room temperature. 2 equiv of HPF6 (1 M in THF) was
added portionwise (ꢂ0.5 equiv each time) at room temperature over 3 h. The
solution was extracted with EtOAc, washed with brine, dried with Na2SO4, and
evaporated in vacuo to give 320 mg (99%) of 9 as an orange oil. 1H NMR
(500 MHz, DMSO): d 7.41–7.14 (m, 46H), 6.94 (4H), 6.83 (2H), 6.76 (2H), 6.54
(2H), 6.35 (2H, H-6), 5.04 (2H), 5.03 (2H), 4.87 (2H), 4.71 (2H), 4.24 (2H, H-2),
added to
a solution of 9 (260 mg, 0.174 mmol) in EtOAc (12 mL). The
suspension was de-gassed under vacuum and then stirred for 3 h under
hydrogen atmosphere (using a balloon). The catalyst was filtered through
Celite, washed with EtOAc, and the solvent was evaporated in vacuo. The
residue was purified by RP-HPLC, 20% to 100% MeOH/water + 0.05% TFA to
yield 1 (31 mg, 0.052 mmol, 30.1% yield). 1H NMR (400 MHz, Acetone): d 6.94
(2H, s), 6.80 (4H, s), 5.97 (2H, s), 4.68 (2H, d, 2 Hz), 4.10–3.98 (2H, m), 3.95 (2H,
s), 2.91 (2H, dd, J1 = 1 Hz, J2 = 6 Hz), 2.54 (2H dd, J1 = 2 Hz, J2 = 4 Hz). .1H NMR
(500 MHz, DMSO): d 9.01–8.62 (8H, –OH), 6.70 (2H, H-20), 6.59 (2H, H-50), 6.44
(2H, H-60), 5.90 (2H, H-6), 4.78 (2H, –OH), 4.39 (2H, H-2), 3.77 (2H, H-3), 3.57
3.97 (2H), 3.77 (s, 2H, CH2), 3.51 (2H, H-3), 2.87 (1H, H-4b), 2.43 (1H, H-4a C
). 13
NMR (125 MHz, DMSO): d 155.55 (C-7), 154.2 (C-5), 152.9 (C-9), 147.9 (C-30, C-
40), 138.3 (Bn-C), 137.6 (Bn-C), 137.1 (Bn-C), 132.4 (C-10), 128.4–127.2 (Bn-CH),
120.1 (C-60), 113.9 (C-50), 113.2 (C-20), 109.7 (C-8), 101.5 (C-4a), 91.4 (C-6),
78.6 (C-2), 74.4 (C-3), 70.4 (CH2), 70.3 (CH2), 69.9 (CH2), 69.5 (CH2), 69.3 (CH2),
25.9 (C-4), 17.0 (CH2, methane). IR (CDCl3, cmꢀ1): 3065, 3033, 2919, 2873,
1606. HRMS (ESI-TOF) m/z calcd for C101H87O12 [M+H]+ 1493.6354, found
(s, 2H, CH2), 2.59 (1H, H-4b), 2.32 (1H, H-4a
). 13C NMR (125 MHz, DMSO): d
153.2 (C-7), 153.2 (C-5), 152.3 (C-9), 144.5 (C-30, C-40), 130.3 (C-10), 117.9 (C-
60), 114.8 (C-50), 114.2 (C-20), 104.5 (C-8), 99.2 (C-4a), 95.0 (C-6), 80.8 (C-2),
66.0 (C-3), 27.7 (C-4), 15.5 (CH2, methane) . IR (CDCl3, cmꢀ1): 3600–2700 (br s),
1606. HRMS (ESI-TOF) m/z calcd for
C
31H29O12 [M+H]+ 593.1659, found
593.1661. ½a 2D5
ꢀ104.1 (c 1.5, MeOH).
ꢁ
17. 3,5,7,30,40-Penta-O-benzyl-8-(2,2,2-trifluoroacetyl)flavan (4): 1H NMR (500 MHz,
CDCl3): d 7.49–7.25 (m, 23H), 7.10–7.07 (m, 2H), 6.99 (br s, 1 H, H-20), 6.94 (d,