1340
K. Karisalmi, A. M. P. Koskinen
PAPER
(4R,5R)-5-{(1S)-2-[(4R,5R,6S)-6-((1R)-2-{[tert-Butyl(dimeth-
yl)silyl]oxy}-1-methylethyl)-2-ethyl-5-methyl-1,3,2-dioxabori-
nan-4-yl]-1-methoxyethyl}4-[(2-methoxyethoxy)methoxy]-3,3-
dimethyldihydrofuran-2(3H)-one (23)
ane–EtOAc) to afford 32 mg (33%) of the pure aldol 18b; Rf = 0.23
(70% EtOAc–hexane, PMA stain); [a]D +5.4 (c 0 1.0, CHCl3).
IR (film): 1711, 1778, 3218 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.03 (3 H, d, PMBOCH2CHCH3R,
J = 7.0 Hz), 1.08 (3 H, d, C=OCHCH3CHOHR, J = 7.1 Hz), 1.23
(3H, s, RCOCCH3CH3COO), 1.24 (3 H, s, RCOCCH3CH3COO),
1.55–1.59 (2 H, m, RCHHOCH2CHOMeR), 2.65–2.72 (1 H, m,
C=OCHCH3CHOHR), 3.07–3.10 (1 H, m, PMBOCH2CHCH3R),
3.29 (1 H, br s, OH), 3.37 (3 H, s, CH3OR), 3.51 (3 H, s,
RCH2CHOCH3CO2R), 3.51–3.56 (2 H, m, CH3OCH2CH2OR),
3.62–3.77 (4 H, m, CH3OCH2CH2OR + PMBOCH2R), 3.78 (3 H, s,
CH3OAr), 3.84–3.88 (1 H, m, RCHOMeR), 3.93 (1 H, d,
The aldol adduct 15b (25 mg, 0.047 mmol) was dissolved in THF–
MeOH (0.75 + 0.1 mL) in a flame-dried flask under argon and the
mixture was cooled in an acetone/dry ice bath (–78 °C). Et2BOMe
(1 M in THF, 51 mL, 0.051 mmol) was added dropwise and the mix-
ture was stirred at –70 °C for 0.5 h. Then NaBH4 (2 mg, 0.051
mmol) was added and the mixture was stirred for 4.5 h (–78 to
–15 °C). Then an additional 0.05 mmol of both reagents (Et2BOMe
and NaBH4) were added and stirring was continued (–15 °C) for an-
other 2.5 h. Then the reaction was quenched with AcOH (0.1 mL)
and the mixture was diluted with EtOAc. The organic layer was
washed with aq sat. Na2CO3, dried (Na2SO4), filtered and the sol-
vent was evaporated to give 24 mg of crude product. The crude
product was purified by flash chromatography (silica gel, 40%
EtOAc–hexane) to furnish 5 mg of the syn boron diol 23 adduct and
8 mg of a mixture of syn and anti diols.
RCHOMEM,
J
=
4.3 Hz), 3.98–4.02 (1 H, m,
C=OCHCH3CHOHR), 4.35–4.40 (1 H, m, R2CHOCOR), 4.69 (1 H,
d, OCHaHbO, J = 6.9 Hz), 4.76 (1 H, d, OCHaHbO, J = 6.9 Hz), 4.81
(2 H, s, MeOArCH2OR), 6.84 (2 H, d, ArH, J = 8.6 Hz), 7.18 (2 H,
d, ArH, J = 8.6 Hz).
13C NMR (100 MHz, CDCl3): d = 12.9, 13.9, 18.9, 23.2, 35.1, 44.6,
45.2, 53.4, 55.2, 59.0, 67.4, 68.5, 69.1, 71.8, 72.2, 73.0, 75.9, 83.1,
83.5, 97.1, 113.7, 129.3, 129.7, 159.2, 180.0, 217.2.
23
Rf = 0.23 (40% EtOAc–hexane, PMA stain); [a]D +5.0 (c = 0.3,
CHCl3).
IR (film): 1779 cm–1.
HRMS: m/z calcd for C28H44O10+ Na: 563.2841; found: 563.2832
(M + Na+).
1H NMR (400 MHz, CDCl3): d = 0.07 [6 H, s, (CH3)2Si], 0.62 (2 H,
q, CH3CH2BR, J = 8.1 Hz), 0.74 (3 H, d, TBDMSOCH2CHCH3R,
J = 6.9 Hz), 0.84 [3 H, d, CHCH3(CHOBR)2, J = 6.6 Hz], 0.86 (3 H,
t, CH3CH2BR, J = 8.1 Hz), 0.90 (9 H, s, t-C4H9Si), 1.26 (3 H, s,
RCOCCH3CH3COO), 1.29 (3 H, s, RCOCCH3CH3COO), 1.45–
1.53 [2 H, m, OBRCHaHbCHOMeR + CHCH3(CHOBR)2], 1.74 (1
H, dt, CHaHbCHOMeR, J = 12.1, 2.2 Hz), 1.91 (1 H, q,
TBDMSOCH2CHCH3R, J = 6.6 Hz), 3.37 (s, 3 H, CH3OR), 3.47–
3.51 (3 H, m, TBDMSOCH2R + CH3OCHaHbCH2OR), 3.58 (3 H, s,
RCH2CHOCH3CO2R), 3.65 (1 H, ddd, CH3OCHaHbCH2OR, J =
10.9, 6.4, 3.1 Hz), 3.69 (1 H, dd, CH3OCH2CHaHbOR J = 9.6, 8.6
Hz), 3.83 (1 H, dt, CHCH3CHOBRCHCH3, J = 10.3, 1.5 Hz), 3.89
(2 H, m, CH3OCH2CHaHbOCH2OR + CHOBRCHCH3CHOBCH2),
3.96 (1 H, d, RCHOMEM, J = 4.1 Hz), 4.04 (1 H, ddd, RCHOMeR,
J = 10.4, 8.2, 2.2 Hz), 4.39 (1 H, dd, R2CHOCOR, J = 8.2, 4.1 Hz),
4.74 (1 H, d, OCHaHbO, J = 7.4 Hz), 4.78 (1 H, d, OCHaHbO, J =
7.4 Hz).
(4R,5R)-5-{(1S)-2-[(4R,5R,6S)-2-Ethyl-6-{(1R)-2-[(4-Methoxy-
benzyl)oxy-1-methylethyl]-5-methyl-1,3,2-dioxaborinan-4-yl}-
1-methoxyethyl]}-4-[(methoxyethoxy)methoxy]-3,3-dimeth-
yldihydrofuran-2(3H)-one (19)
The aldol adduct 18b (42 mg, 0.078 mmol) was dissolved in THF–
MeOH (0.7 + 0.1 mL) under argon in a flame-dried flask and the
mixture was cooled in an acetone/dry ice bath (–78 °C). Then
Et2BOMe (1 M in THF, 0.156 mmol, 0.156 mL) was added drop-
wise and the mixture was stirred for 1 h 10 min (–70 to –78 °C) be-
fore the addition of NaBH4 (3 mg, 0.086 mmol). After 2 h 50 min
(–65 to –78 °C) the reaction was quenched with H2O and the mix-
ture was extracted with EtOAc (4 ×). The combined organic phases
were dried (Na2SO4), filtered and the solvent was evaporated to give
42 mg of crude product. After purification by flash chromatogra-
phy, 16 mg of the syn boron diol adduct 19 was obtained; Rf = 0.41
(70% EtOAc–hexane, PMA stain); [a]D +7.7 (c = 1.0, CHCl3).
IR (film): 1778 cm–1.
13C NMR (100 MHz, CDCl3): d = –5.4, 7.8, 8.4, 12.6, 18.3, 19.0,
23.1, 25.9, 35.8, 36.9, 37.8, 45.4, 59.1, 60.4, 65.2, 66.3, 68.5, 71.8,
71.9, 74.7, 75.0, 82.7, 84.1, 96.8, 180.0.
1H NMR (400 MHz, CDCl3): d = 0.60 (2 H, q, CH3CH2BR, J = 8.0
Hz), 0.80 (3 H, d, PMBOCH2CHCH3R, J = 6.8 Hz), 0.84 [3 H, d,
CHCH3(CHOBR)2, J = 6.6 Hz], 0.86 (3 H, t, CH3CH2BR, J = 8.0
Hz), 1.26 (3 H, s, RCOCCH3CH3COO), 1.27 (3 H, s,
RCOCCH3CH3COO), 1.45–1.55 [2 H, m, CHaHbCHOMeR +
R2CHCH3(CHOBR)2], 1.74 (1 H, dt, CHaHbCHOMeR, J = 10.6, 2.4
Hz), 2.08 (1 H, q, PMBOCH2CHCH3R, J = 6.3 Hz), 3.36 (3 H, s,
CH3OR), 3.33–3.38 (1 H, m, PMBOCHaHbR), 3.47–3.51 (2 H, m,
HRMS: m/z calcd for C28H55BO9Si + Na: 597.3606; found:
597.3604 (M + Na+).
(4R,5R)-5-{(1S,3R,4R,6R)-3-Hydroxy-1-methoxy-7-[(4-meth-
oxybenzyl)oxy]-4,6-dimethyl-5-oxoheptyl}-4-[(2-methoxy-
ethoxy)methoxy]-3,3-dimethyldihydrofuran-2(3H)-one (18b)
(Chx)2BCl (1 M in THF, 0.19 mL, 0.185 mmol) was dissolved in
anhyd Et2O (1.0 mL) under argon in a flame-dried flask and Et3N
(28 mL, 0.19 mmol) was added dropwise. The mixture was cooled
in an ice bath and then the ketone 17 (42 mg, 0.177 mmol) in Et2O
(1.0 mL) was added. This mixture was stirred at 0 °C for 1 h, then
the ice bath was replaced with an acetone/dry ice bath (–78 °C) and
the mixture was allowed to cool before the addition of the aldehyde
2 (56 mg, 0.18 mmol) in Et2O (1.0 mL). After stirring for 3 h 15 min
at –78 °C, the flask containing the reaction mixture was moved to a
room cooled to –18 °C and allowed to stay there overnight. Next
morning (total reaction time 21 h) the reaction was quenched with
aq sat. NH4Cl and the mixture was extracted with Et2O (3 ×). The
combined organic phases were dried (Na2SO4), filtered and the sol-
vent was evaporated to give 157 mg of crude product. The crude
product was purified by flash chromatography (silica gel, 60% hex-
PMBOCHaHbR
+
CH3OCHaHbCH2OR), 3.57 (3 H, s,
RCH2CHOCH3CO2R), 3.59 (1 H, t, CH3OCHaHbCH2OR, J = 8.9
Hz), 3.63 (1 H, ddd, CH3OCH2CHaHbOR, J = 3.2, 6.4, 11.1 Hz),
3.80 (3 H, s, CH3OAr), 3.85–3.90 (3 H, m, RBOCHCHMeCHOBR
+ CH3OCH2CHaHbOR), 3.97 (1 H, d, RCHOMEM, J = 4.1 Hz),
4.02 (1 H, dt, RCHOMeR, J = 8.1, 2.4 Hz), 4.38 (1 H, dd,
R2CHOCOR, J = 8.1 4.1 Hz), 4.74 (1 H, d, OCHaHbO, J = 7.4 Hz),
4.78 (1 H, d, OCHaHbO, J = 7.4 Hz), 4.81 (2 H, s, MeOArCH2OR),
6.88 (2 H, d, ArH, J = 8.6 Hz), 7.27 (2 H, d, ArH, J = 8.6 Hz).
13C NMR (100 MHz, CDCl3): d = 7.8, 8.8, 12.5, 19.0, 23.2, 25.6,
34.5, 35.9, 37.9, 45.4, 55.3, 59.1, 60.5, 68.5, 71.8, 72.0, 72.6, 72.8,
75.0, 75.3, 82.7, 84.0, 96.8, 113.8, 129.1, 130.8, 159.1, 180.0.
HRMS: m/z calcd for C30H49BO10 + Na: 603.3316; found: 603.3317
(M + Na+).
Synthesis 2004, No. 9, 1331–1342 © Thieme Stuttgart · New York