The Journal of Organic Chemistry
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17.4 mmol, 1.00 equiv) was added at 0 °C, and the mixture was stirred
at room temperature for 1 h until a clear solution was obtained.
Me3NO·2H2O (3.87 g, 34.9 mmol, 2.00 equiv) was added slowly
(caution: exothermic reaction!), followed after 1 h by the addition of
‘diol’ (7.93 g, 17.4 mmol, 1.00 equiv). The reaction mixture was stirred
overnight. The solvent was removed under reduced pressure, and the
crude product was subjected to flash column chromatography
(petroleum ether/ethyl acetate 90:10). A colorless foam of the title
compound was obtained (10.5 g, 15.9 mmol, 91%). Rf = 0.44
(petroleum ether/ethyl acetate 95:5). [α]2D0 = −90.7 (c 1.8, CHCl3).
Melting range 74−83 °C. 1H NMR (600 MHz, CDCl3): δ 0.00 [s, 6H,
Si(CH3)2], 0.85 [s, 9H, C(CH3)3], 1.19 [d, 6H, C(CH3)2], 3.05 (s,
6H, OCH3), 5.19 (d, J = 18.1 Hz, 1H, 4-H), 5.38 (s, 2H, 4′-H, 5′-H),
6.26 (d, J = 18.1 Hz, 1H, 3-H), 7.29−7.42 (m, 20H, arom. CH). 13C
NMR (151 MHz, CDCl3): δ 0.00 [Si(CH3)2], 28.0 [C(CH3)3], 31.8
(CH3), 32.0 (C-1), 53.9, 54.0 (OCH3), 76.0 (C-2), 79.8 (C-4′, C-5′),
85.5 (CPh2OCH3), 114.7 (C-4), 129.4, 129.6, 129.9, 130.6, 131.9
(arom. CH), 143.3, 143.6 (arom. Cipso), 162.8 (C-3). IR (film) νmax
[cm−1] = 3059, 2926, 2851, 1640, 1494, 1446, 1387, 1347, 1229, 1181,
1075, 1034, 1017, 967, 920, 886, 835, 773, 757, 733, 698. HRMS (ESI
+, m/z): [M + Na]+ calcd for C41H51BO5SiNa, 685.3497; found,
685.3494.
min, reaching a temperature of 160 °C. After removal of volatile
compounds under reduced pressure, flash column chromatography
(petroleum ether/ethyl acetate 85:15) led to a mixture of
diastereomers 4 and 5 (25 mg, 0.04 mmol, 23%) and starting material
3 (62 mg, 0.11 mmol, 56%).
Allylboronate 4: Rf = 0.18 (petroleum ether/ethyl acetate 95:5).
[α]2D0 = −103.2 (c 0.8, CHCl3). Melting range 63−69 °C. H NMR
1
(600 MHz, CDCl3): δ 1.05 (t, J = 7.2 Hz, 3H, 2″-H), 1.25 (s, 3H,
CH3), 1.45 (s, 3H, 6-H), 1.76 (dd, J = 15.0, 10.7 Hz, 1H, 2-Ha), 1.94
(ddd, J = 10.7, 10.1, 4.3 Hz, 1H, 3-H), 2.03 (dd, J = 15.0, 4.3 Hz, 1H,
2-Hb), 2.92 (s, 6H, OCH3), 3.85 (q, J = 7.2 Hz, 1H, 1″-H), 4.58 (d, J =
10.1 Hz, 1H, 4-H), 5.20 (s, 2H, 4′-H, 5′-H), 7.17−7.28 (m, 20H,
arom. CH). 13C NMR (151 MHz, CDCl3): δ 14.1 (C-2″), 17.9 (C-6),
20.5 (br, C-3), 25.7 (CH3), 29.6 (CH3), 35.4 (C-2), 51.7 (OCH3),
59.9 (C-1″), 77.8 (C-4′, C-5′), 83.3 (CPh2OCH3), 123.3 (C-4), 127.3,
127.5, 127.7, 128.5, 129.7 (arom. CH), 131.2 (C-5), 141.3 (arom.
Cipso), 173.5 (C-1). IR (film) νmax [cm−1] = 3059, 2967, 2937, 2830,
1735, 1495, 1447, 1369, 1331, 1272, 1232, 1200, 1137, 1076, 1033,
967. 922, 901, 828, 795, 759, 733, 700. HRMS (ESI+, m/z): [M +
Na]+ calcd for C39H43BO6Na, 641.3050; found, 641.3045.
Allylboronate 5: Rf = 0.18 (petroleum ether/ethyl acetate 95:5).
[α]2D0 = −107.5 (c 0.8, CHCl3). Melting range 63−69 °C. H NMR
1
(600 MHz, CDCl3): δ 1.06 (t, J = 7.1 Hz, 3H, 2″-H), 1.26 (d, J = 1.4
Hz, 3H, CH3), 1.46 (d, J = 1.4 Hz, 3H, 6-H), 1.82 (dd, J = 15.5, 11.4
Hz, 1H, 2-Ha), 1.94 (dd, J = 15.5, 3.8 Hz, 1H, 2-Hb), 1.94 (ddd, J =
11.4, 10.3, 3.8 Hz, 1H, 3-H), 2.91 (s, 6H, OCH3), 3.86 (dq, J = 11.3,
7.1 Hz, 1H, 1″-Ha), 3.90 (dq, J = 11.3, 7.1 Hz, 1H, 1″-Hb), 4.48 (dq, J
= 10.3, 1.3 Hz, 1H, 4-H), 5.21 (s, 2H, 4′-H, 5′-H), 7.16−7.27 (m,
20H, arom. CH). 13C NMR (151 MHz, CDCl3): δ 14.2 (C-2″), 17.9
(C-6), 20.6 (br, C-3), 25.8 (CH3), 35.7 (C-2), 51.8 (OCH3), 59.9 (C-
1″), 77.9 (C-4′, C-5′), 83.4 (CPh2OCH3), 123.0 (C-4), 127.2, 127.3,
127.5, 127.8, 128.5, 129.7 (arom. CH), 131.3 (C-5), 141.3, 141.4
(arom. Cipso), 173.4 (C-1). IR (film) νmax [cm−1] = 3059, 2967, 2937,
2834, 1734, 1495, 1447, 1369, 1331, 1269, 1233, 1199, 1137, 1075,
1033, 967, 922, 901, 828, 796, 758, 734, 700. HRMS (ESI+, m/z): [M
+ Na]+ calcd for C39H43BO6Na, 641.3050; found, 641.3044.
(4′R,5′R,3E)-4-[4′,5′-Bis(methoxydiphenylmethyl)-1′,3′,2′-dioxa-
borolan-2′-yl]-2-methylbut-3-en-2-ol (3). TBS-protected boronic
ester 1 (6.10 g, 9.20 mmol, 1.00 equiv) was dissolved in CH2Cl2/
MeOH (70 mL), and a solution of HCl (0.85 mL, 27.6 mmol, 3.00
equiv) in MeOH (13 mL) was added dropwise. The mixture was
stirred at room temperature for 4 h. The reaction mixture was
quenched with sat. aq. NaHCO3 (10 mL), and the solvents were
reduced under pressure. H2O was added, and the separated aqueous
phase was extracted three times with Et2O. The combined organic
layers was washed successively with brine and dried over MgSO4.
Filtration and subsequent removal of the solvent under reduced
pressure gave a yellowish oil, which was subjected to flash
chromatography to provide 3 (3.38 g, 6.16 mmol, 67%) as a colorless
foam along with recovery of 30% of the starting material 1. Rf = 0.28
(petroleum ether/ethyl acetate 85:15). [α]2D0 = −68.8 (c 0.5, CHCl3).
(4′R,5′R)-3-[4′,5′-Bis(methoxydiphenylmethyl)-1′,3′,2′-dioxabor-
olan-2′-yl]-5-methylhex-4-enol (6). Under an atmosphere of dry
nitrogen, the mixture of allylboronates 4 and 5 (105 mg, 0.17 mmol,
1.00 equiv) was dissolved in anhydrous THF (1.7 mL) in a Schlenk
flask. After addition of 4 Å MS, the reaction mixture was cooled to −78
°C, and DiBAlH (153 μL, 0.85 mmol, 5.00 equiv) was added
dropwise. The mixture was stirred at room temperature, and the end
of the reaction was judged by TLC (3 h). After dilution with Et2O, the
reaction was quenched with H2O (0.3 mL), 2 M NaOH (0.5 mL), and
H2O (0.3 mL) and extracted several times. The combined organic
layers were dried over MgSO4 and filtered, and the solvent was
removed under reduced pressure. The crude product was subjected to
flash column chromatography (petroleum ether/ethyl acetate 85:15)
to yield a mixture of diastereomers 6 (77 mg, 0.13 mmol, 79%) as a
colorless foam. Rf = 0.31 (petroleum ether/ethyl acetate 85:15). [α]D20
1
Melting range 97−100 °C. H NMR (600 MHz, CDCl3): δ 1.10 (s,
3H, CH3), 1.10 (s, 3H, CH3), 2.93 (s, 6H, OCH3), 5.12 (d, J = 18.2
Hz, 1H, 4-H), 5.28 (s, 2H, 4′-H, 5′-H), 6.22 (d, J = 18.2 Hz, 1H, 3-H),
7.17−7.29 (m, 20H, arom. CH). 13C NMR (151 MHz, CDCl3): δ 29.0
(CH3), 29.2 (C-4), 51.8 (OCH3), 71.7 (C-3), 77.7 (C-4′, C-5′), 83.4
(CPh2OCH3), 112.7 (C-1), 127.3, 127.3, 127.5, 127.8, 128.5, 129.7
(arom. CH), 141.1, 141.4 (arom. Cipso), 159.4 (C-2). 11B NMR (192
MHz, CDCl3): δ 29.4. IR (film) νmax [cm−1] = 3385, 3058, 2973, 2834,
1638, 1494, 1446, 1398, 1368, 1345, 1240, 1187, 1150, 1075, 1033,
1016, 966, 905, 849, 831, 795, 757, 735, 698. HRMS (ESI+, m/z): [M
+ Na]+ calcd for C35H37BO5Na, 571.2632; found, 571.2624. Anal.
Calcd for C35H37BO5 (548.2734): C 76.64, H 6.80. Found: C 76.31, H
6.83.
[3,3]-Sigmatropic Rearrangements. (3S,4′R,5′R)- and
(3R,4′R,5′R)-Ethyl 3-[4′,5′-Bis(methoxydiphenylmethyl)-1′,3′,2′-
dioxaborolan-2′-yl]-5-methylhex-4-enoate (4 and 5): Method A
(Johnson Rearrangement). In a two-neck round-bottom flask
equipped with a Claisen condenser under a nitrogen atmosphere,
allyl alcohol 3 (700 mg, 1.28 mmol, 1.00 equiv) was treated with
triethyl orthoacetate (1.64 mL, 8.96 mmol, 7.00 equiv) and a catalytic
amount of propionic acid (5.50 μL, 0.07 mmol). The reaction mixture
was heated at 135 °C and stirred for 4 h while formed EtOH was
1
= −127.7 (c 0.8, CHCl3). Melting range 73−78 °C. H NMR (600
MHz, CDCl3): δ 1.13−1.18 (m, 2H, OH, 2-Ha), 1.28−1.33 (m, 1H, 2-
Hb), 1.34 (d, J = 1.0 Hz, 3H, CH3), 1.48 (d, J = 1.0 Hz, 3H, 6-H), 1.55
(td, J = 5.1, 10.1 Hz, 1H, 3-H), 2.92 (s, 6H, OCH3), 3.20 (dt, J = 10.6,
6.8 Hz, 1H, 1-Ha), 3.28 (dt, J = 10.6, 6.8 Hz, 1H, 1-Hb), 4.54 (dp, J =
10.1, 1.3 Hz, 1H, 4-H), 4.64−4.66 (m, 1H, 4-H), 5.21 (s, 2H, 4′-H, 5′-
H), 7.17−7.27 (m, 20H, arom. CH). 13C NMR (151 MHz, CDCl3): δ
17.9 (C-6), 20.8 (br, C-3), 25.8 (CH3), 33.7 (C-2), 51.8 (OCH3), 62.6
(C-1), 77.6 (C-4′, C-5′), 83.4 (CPh2OCH3), 124.5 (C-4), 127.2,
127.3, 127.5, 127.8, 128.5, 129.7 (arom. CH), 130.6 (C-5), 141.3,
141.4 (arom. Cipso). IR (film) νmax [cm−1] = 3402, 3059, 2935, 1495,
1447, 1375, 1340, 1232, 1200, 1137, 1076, 1033, 967, 922, 901, 828,
795, 759, 733, 700. HRMS (ESI+, m/z): [M + Na]+ calcd for
C37H41BO5Na, 599.2945; found, 599.2941.
1
removed. The dr, measured by H NMR spectroscopy, was shown to
be 46:54. After flash column chromatography (petroleum ether/ethyl
acetate 85:15) a mixture of diastereomers was obtained (420 mg, 0.68
mmol, 53%). Several rounds of MPLC (petroleum ether/ethyl acetate
97:3, 98:2, 99:1) gave 4 as a pure white solid and a mixture containing
91% 5 and 9% 4.
Method B (Microwave). In a microwave vessel equipped with a stir
bar, allyl alcohol 3 (100 mg, 0.18 mmol, 1.00 equiv) was dissolved in
DMF (300 μL). Triethyl orthoacetate (332.71 μL, 1.82 mmol, 10.00
equiv) and a catalytic amount of propionic acid (0.80 μL, 0.01 mmol)
were added, and the mixture was heated in a microwave reactor for 34
(3S,4′R,5′R)- and (3R,4′R,5′R)-N,N-Dimethyl-3-[4′,5′-bis(meth-
oxydiphenylmethyl)-1′,3′,2′-dioxaborolan-2′-yl]-5-methylhex-4-en-
amide (7 and 8). Into a two-neck round-bottom flask equipped with a
Claisen condenser, allyl alcohol 3 (9.0 g, 16.41 mmol, 1.00 equiv) was
dissolved in toluene (33 mL), and N,N-dimethylacetamide dimethy-
11555
dx.doi.org/10.1021/jo402130u | J. Org. Chem. 2013, 78, 11549−11559