Organocatalysis in Natural Product Synthesis
FULL PAPERS
ES+): m/z=286.1787, calcd. for C16H25NO2 [M+Na]+:
286.1783; [a]2D0:+7.9 (c 1.00, CH2Cl2).
2H), 4.62–4.56 (m, 1H), 4.43–4.38 (m, 1H), 3.72–3.64 (m,
1H), 2.05 (d, J=4.6 Hz, 1H), 2.00–1.92 (m, 1H), 1.83–1.75
(m, 1H), 1.60–1.48 (m, 2H), 0.97 (t, J=7.4 Hz, 3H);
13C NMR: d=166.1, 139.4, 131.0 (2C), 128.7 (2C), 128.5,
69.9, 62.5, 36.0, 30.3, 9.9; MS (TOF ES+): m/z=265.0612,
calcd. for C12H15O3Cl [M+Na]+: 265.0607; [a]D20: À15.5 (c
1.02, CH2Cl2).
Nonane-1,3-diol (10a): The product was obtained follow-
ing the general procedure B. The enantiomeric excess was
determined by HPLC using a Daicel Chiralpak OJ column
on the corresponding mono-4-chlorobenzoylated 1,3-diol ac-
cording to general procedure D [hexane/i-PrOH (95/5)]:
flow rate 1.0 mLminÀ1: tminor =5.0 min, tmajor =5.5 min (94%
AHCTUNGTREG(NNNU trans)-Non-6-ene-1,3-diol (10e): The product was ob-
1
ee); H NMR: d=3.90–3.79 (m, 3H), 2.36 (s, 1H), 2.29 (s,
tained following the general procedure B. The enantiomeric
excess was determined by HPLC using a Daicel Chiralpak
OJ column on the corresponding mono-4-chlorobenzoylated
1,3-diol according to general procedure D [hexane/i-PrOH
1H), 1.74–1.17 (m, 12H), 0.87 (t, 3H, J=6.7 Hz); 13C NMR:
d=71.8, 61.3, 38.1, 37.7, 31.7, 29.3, 25.5, 22.5, 14.0; MS
(TOF ES+): m/z=183.1358, calcd. for C9H20O2 [M+Na]+:
183.1361; [a]2D0: À5.9 (c 1.07, CH2Cl2) {lit: [a]2D0: À5.2 (c 0.10,
MeOH)}.[17]
(95/5)]: flow rate 1.0 mLminÀ1
: tminor =8.0 min, tmajor =
9.1 min (91% ee); 1H NMR: d=5.44–5.32 (m, 2H), 3.92–
3.80 (m, 3H), 2.40 (s, 2H), 2.22–1.98 (m, 4H), 1.76–1.49 (m,
4H), 0.96 (t, 3H, J=7.5 Hz); 13C NMR: d=132.4, 128.3,
72.0, 61.7, 38.2, 37.5, 23.3, 20.5, 14.3; MS (TOF ES+): m/z=
181.1204, calcd. for C9H18O2 [M+Na]+: 181.1204; [a]D20: +1.7
(c 1.06, CH2Cl2).
Heptane-1,3-diol (10b): The product was obtained follow-
ing the general procedure B. The enantiomeric excess was
determined by HPLC using a Daicel Chiralpak OJ column
on the corresponding mono-4-chlorobenzoylated 1,3-diol ac-
cording to general procedure D [hexane/i-PrOH (97/3)]:
flow rate 1.0 mLminÀ1
: tmajor =17.0 min, tminor =15.2 min
4-(Benzyloxy)butane-1,3-diol (10f): The product was ob-
tained following the general procedure B. The enantiomeric
excess was determined by HPLC using a Daicel Chiralpak
AS column on the corresponding mono-4-chlorobenzoylated
1,3-diol according to general procedure D [hexane/i-PrOH
1
(92% ee); H NMR; d=3,91–3,80 (m, 3H), 2.34 (br s, 1H),
2.20 (br s, 1H), 1.75–1.23 (m, 8H), 0.91 (t, J=6.8 Hz, 3H);
13C NMR: d=72.7, 62.2, 38.4, 37.7, 27.8, 22.8, 14.2; MS
(TOF ES+): m/z= 155.1046, calcd. for C7H16O2 [M+Na]+:
155.1048; [a]2D0: À1.7 (c 0.18, CH2Cl2) {lit: [a]2D0: À1.94 (c
1.64, CHCl3)}.[18]
(90/10)]: flow rate 1.0 mLminÀ1: tminor =15.1 min, tmajor
=
1
10.9 min (95% ee); H NMR: d=7.38–7.28 (m, 5H), 4.56 (s,
2H), 4.09–4.03 (m, 1H), 3.82 (t, 2H, J=5.4 Hz), 3.50 (dd,
1H, J=3.6 Hz, 9.5 Hz), 3.40 (dd, 1H, J=7.5 Hz, 9.5 Hz),
2.58 (s, 2H), 1.76–1.65 (m, 2H); 13C NMR: d=137.8, 128.5
(2C), 127.8, 127.7 (2C), 74.3, 73.4, 70.2, 60.9, 34.8; MS (TOF
ES+): m/z=219.0997, calcd. for C11H16O3 [M+Na]+:
219.0997; [a]2D0: +9.0 (c 1.01, CH2Cl2) {lit: [a]2D0: +8.98 (c
0.88, MeOH)}.[20]
Hexane-1,3-diol (10c): The product was obtained follow-
ing the general procedure B. The enantiomeric excess was
determined by HPLC using a Daicel Chiralpak OJ column
on the corresponding mono-4-chlorobenzoylated 1,3-diol ac-
cording to general procedure D [hexane/i-PrOH (95/5)]:
flow rate 1.0 mLminÀ1: tminor =8.5 min, tmajor =9.7 min (92%
1
ee); H NMR: d=3.90–3.78 (m, 3H), 2.60 (s, 2H), 1.74–1.60
(m, 2H), 1.53–1.33 (m, 4H), 0.92 (t, 3H, J=7.1 Hz);
13C NMR: d=72.0, 61.8, 39.9, 38.2, 18.7, 14.0; MS (TOF
ES+): m/z=141.0891, calcd. for C6H14O2 [M+Na]+:
141.0891; [a]2D0: À1.9 (c 1.11, CH2Cl2) {lit: [a]2D0: M>->0.75
(c 0.67, CHCl3)}.[19]
1-Phenylhexane-1,3-diol (11a): The product was obtained
following the general procedure C in a 1:1 diastereomeric
mixture. The enantiomeric excess was determined by HPLC
using a Daicel Chiralpak AD column on the corresponding
mono-4-chlorobenzoylated 1,3-diol according to general pro-
3-Hydroxypentyl 4-chlorobenzoate (10’d): (E)-Benzalde-
hyde oxime (181 mg, 1.50 mmol) was added at 48C to a
stirred solution of the catalyst (15 mg, 0.025 mmol),
PhCO2H (3 mg, 0.025 mmol) and aldehyde (49 mL,
0.5 mmol) in toluene (250 mL). After complete consumption
cedure D [hexane/i-PrOH (95/5)]: flow rate 1.0 mLminÀ1
:
tminor =13.3 min, tmajor =14.6 min (94% ee); 1H NMR: d=
7.34–7.23 (m, 10H), 5.02 (dd, 1H, J=3.3 Hz, 8.1 Hz), 4.89
(dd, 1H, J=3.8 Hz, 9.3 Hz), 3.95–3.81 (m, 2H), 3.52 (s, 2H),
2.84 (s, 2H), 1.91–1.72 (m, 4H), 1.54–1.29 (m, 8H), 0.90 (dt,
6H, J=6.0 Hz, 12.1 Hz); 13C NMR: d=144.6, 144.5, 128.4
(2C), 128.3 (2C), 127.5, 127.2, 125.6 (2C), 125.5 (2C), 75.3,
72.5, 71.5, 68.9, 45.2, 44.5, 40.1, 39.5, 18.8, 18.4, 14.0 (2C);
MS (TOF ES+): m/z=217.1195, calcd. for C12H18O2 [M+
Na]+: 217.1204.
1
of the aldehyde (as monitored by H NMR spectroscopy),
the reaction mixture was cooled to 08C and flushed with N2,
before addition of a 1M solution of LiAlH4 in THF (2 mL).
The reaction mixture was stirred overnight at room temper-
ature under N2. The reaction was quenched by careful addi-
tion of H2O (4 mL). The organic layer was collected and the
aqueous phase extracted with CH2Cl2 (3ꢁ10 mL). The com-
bined organic phases were dried over MgSO4, filtered and
evaporated at low pressure. The crude product was dissolved
in CH2Cl2 (2 mL) and added 4-chlorobenzoyl chloride
(0.64 mL, 5.0 mmol) and Et3N (0.70 mL, 5.0 mmol). The re-
action mixture was stirred over night, and evaporated to
dryness under vacuum. FC (EtOAc/pentane 1:4) gave the
pure product. The enantiomeric excess was determined by
HPLC using a Daicel Chiralpak OJ column on the corre-
sponding mono-4-chlorobenzoylated 1,3-diol according to
general procedure D [hexane/i-PrOH (98/2)]: flow rate
1.0 mLminÀ1: tmajor =11.8 min, tminor =13.3 min (95% ee);
1H NMR: d=7.96 (d, J=8.5 Hz, 2H), 7.41 (d, J=8.5 Hz,
2-Methyloctane-3,5-diol (11b): The product was obtained
following the general procedure C in a 1:1 diastereomeric
mixture. The enantiomeric excess was determined by HPLC
using a Daicel Chiralpak AD column on the corresponding
mono-4-chlorobenzoylated 1,3-diol according to general pro-
cedure D [hexane/i-PrOH (95/5)}: flow rate 1.0 mLminÀ1
:
tminor =9.3 min, tminor =11.8 min (94% ee); 1H NMR: d=
3.99–1.91 (m, 1H), 3.89–3.82 (m, 1H), 3.71–3.62 (m, 2H),
2.93 (s, 2H), 2.78 (s, 2H), 2.20–2.13 (m, 2H), 1.73–1.32 (m,
12H), 0.96–0.90 (m, 18H); 13C NMR: d=78.0, 73.8, 73.0,
69.9, 40.4, 39.5, 39.3, 39.2, 34.2, 33.7, 19.0, 18.6, 18.5, 18.2,
18.0, 17.4, 14.0, 14.0; MS (TOF ES+): m/z=183.1359, calcd.
for C9H20O2 [M+Na]+: 183.1361.
Adv. Synth. Catal. 2009, 351, 3193 – 3198
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3197