A stereoselective synthesis of the reported structure of polyporolide

Article abstract of DOI:10.1039/c5ra07930f

Polyporolide, isolated from a basidiomycete, was assigned a 4-hydroxy-5-(1-hydroxyhexyl)-dihydrofuran-2-one structure with anti-placement of the three contiguous stereocenters. A stereoselective total synthesis of the reported structure of the natural product involving two different routes is presented. A comparison of the spectral data of the synthesized molecule indicates the need for structure revision of natural polyporolide.

Full text of DOI:10.1039/c5ra07930f

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A stereoselective synthesis of the reported
structure of polyporolide†
Cite this: RSC Adv., 2015, 5, 49189
*
Pradnya H. Patil and Rodney A. Fernandes
Polyporolide, isolated from a basidiomycete, was assigned a 4-hydroxy-5-(1-hydroxyhexyl)-dihydrofuran-
2-one structure with anti-placement of the three contiguous stereocenters. A stereoselective total
synthesis of the reported structure of the natural product involving two different routes is presented. A
comparison of the spectral data of the synthesized molecule indicates the need for structure revision of
natural polyporolide.
Received 30th April 2015
Accepted 26th May 2015
DOI: 10.1039/c5ra07930f
www.rsc.org/advances
Results and discussion
Introduction
Our detailed retrosynthetic approach for polyporolide 1 is out-
lined in Scheme 1. We visualized the g-butyrolactone moiety in
1 can be accessed from 2 by aldol-type acetate anion addition
and cyclization. Compound 2 with anti-diol group can be
accessed from epoxide 3. The latter can be derived from (E)-2-
octen-1-ol 6 through Sharpless asymmetric epoxidation.3 Alter-
natively, (S)-1-octen-3-ol 5 can be derived from 2. From this,
homoacrylate ester formation and ring closing metathesis
would give 4. cis-Dihydroxylation4 of olen 4 and trans-lactoni-
zation was expected to give 1.
The secondary metabolites generated by Polyporus species
(basidiomycetes) are structurally diverse and biologically
active. In 2006, Wei and co-workers isolated a new acetoge-
nin, polyporolide 1 (Fig. 1) from the mycelial solid cultures of
Polyporus strain SC0652.1 They observed this strain to
possess antibacterial activity against E. coli. Polyporolide
showed weak activity against brine shrimps (Artemia salina)
with LC50 of 424.5 mg mLꢀ1. The structure of 1 was estab-
lished by extensive spectroscopic studies. The relative
conguration in 1 was assigned based on the NMR data and
NOESY studies. They observed that H-3 and H-4 were anti-
congured. Similarly, H-4 and H-5 were erythro-congured as
shown in Fig. 1.1
In the course of our synthetic studies directed toward the
enantioselective synthesis of pharmacologically active natural
products like paraconic acids and butyrolactones,2 we became
interested in synthesis of the newly isolated acetogenin, poly-
porolide 1.
Fig. 1 Polyporolide 1.
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400
076, Maharashtra, India. E-mail: rfernand@chem.iitb.ac.in; Web: http://www.chem.
iitb.ac.in/ꢁrfernand/default.htm; Fax: +91-22-25767152; Tel: +91-22-25767174
† Electronic supplementary information (ESI) available: Copies of 1H and 13C
NMR spectra for all the compounds. See DOI: 10.1039/c5ra07930f
Scheme 1 Retrosynthetic analysis for polyporolide 1.
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The forward synthesis of polyporolide started from known
(E)-2-octen-1-ol 65 (Scheme 2). The Sharpless asymmetric epox-
idation,3 of 6 in presence of (+)-DIPT, Ti(Oi-Pr)4 and TBHP in
ꢂ
CH2Cl2 at ꢀ30 C furnished the epoxy alcohol 3 in 85% yield
and excellent >98% ee.6 Regioselective opening of epoxide ring
under Payne rearrangement7 conditions delivered the anti-triol
7 in 71% yield. Monoprotection of primary alcohol as silyl ether
(8, 76%) and acetonide protection of the internal diol furnished
9 (82%). Removal of TBS protection with TBAF liberated the
primary alcohol 2 in 86% yield. The two carbon homologation
was planned through aldol-type acetate anion addition. We
anticipated as reported in literature8 the acetate anion addition
on such vicinal acetonide containing aldehydes to deliver anti-
C3/C4 steroegenic centres. DMP (Dess–Martin periodinane)
oxidation of primary alcohol 2 to aldehyde and subsequent
addition of lithiated ethyl acetate gave diastereoselectively 10 as
single diastereomer in 54% yield over two steps. Removal of
acetonide protection and in situ lactonization produced poly-
porolide 1 in 77% yield, [a]2D5 ¼ +4.5 (c ¼ 0.1, MeOH). The IR
spectral data of 1 was conclusive of g-lactone structure (n ¼
Scheme
3
Alternative synthesis of polyporolide 1: reagents and
conditions: (a) (i) PPh3, imidazole, I2, THF, rt, 3 h, 93%, (ii) Zn, AcOH,
Et2O, rt, 4 h, 86%; (b) DCC, DMAP, CH2Cl2, 11, 0 ꢂC to rt, 6 h, 70%; (c)
Grubbs-II cat. (1 mol%), CH2Cl2, reflux, 12 h, 96%; (d) K3Fe(CN)6,
1
1770 cmꢀ1 for C]O). However, a comparison of H-NMR and
13C-NMR data for synthesized 1 with that reported for the K2CO3, MeSO2NH2, (DHQ)2PHAL, K2OsO4$2H2O, t-BuOH/H2O (1 : 1),
natural product1 showed discrepancy.
0
ꢂC, 24 h, 71%.
We explored an alternative strategy for polyporolide 1 as
shown in Scheme 3. The acetonide alcohol 2 (from Scheme 2)
was converted into iodide and subsequent zinc-mediated
elimination provided (S)-1-octen-3-ol 5 in 80% yield from 2.
Esterication of 5 with 3-butenoic acid 11 under Steglich
conditions9 provided the diene 12 in 70% yield. The ring-closing
metathesis10 of diene 12 with Grubbs-II catalyst (1.0 mol%) gave
d-lactone 4 in excellent yields of 96%. The subsequent Sharpless
asymmetric dihydroxylation4 with (DHQ)2-PHAL ligand gave the
diol and in situ trans-lactonization (from 6-membered to
5-membered lactone) furnished polyporolide 1, [a]2D5 ¼ +4.7 (c ¼
Scheme 2 Synthesis of polyporolide 1: reagents and conditions: (a)
Ti(O-iPr)4, TBHP, (+)-DIPT, CH2Cl2, ꢀ30 ꢂC, 12 h, 85%; (b) 0.5N NaOH,
1,4-dioxane, reflux, 48 h, 71%; (c) TBSOTf, Et3N, THF, 0 ꢂC to rt, 5 min,
76%; (d) (OMe)2C(Me)2, p-TsOH$2H2O, CH2Cl2, rt, 4 h, 82%; (e) TBAF,
THF, 0 ꢂC to rt, 3 h, 86%; (f) (i) DMP, CH2Cl2, rt, 3 h (ii) DIPA, n-BuLi,
THF, ꢀ78 ꢂC, 30 min, then EtOAc, ꢀ78 ꢂC, 25 min, then aldehyde from Fig. 2 Chemical shifts values (d ppm) for molecules related to poly-
2, ꢀ78 ꢂC, 4 h, 54% (two steps); (g) 4N HCl, MeOH, reflux, 8 h, 77%.
porolide 1.
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0.1, MeOH). The spectral data of this was same as that prepared (0.12 mL, 0.406 mmol, 0.2 equiv.). The suspension was cooled to
in Scheme 2.
ꢀ30 ꢂC and allyl alcohol 6 (0.260 g, 2.03 mmol) was added. The
The 1H NMR data for C3, C4 and C5 protons (chemical shis reaction mixture was then stirred for an additional 30 min, and
values, d ppm) for polyporolide 1,1 synthetic 1, and related then t-BuOOH (3.8 M solution in decane, 1.1 mL, 4.1 mmol,
compounds: (+)-mupirocin H 13,11 (ꢀ)-muricatacin 1412 and 2 equiv.) was added. The reaction mixture was stirred to ꢀ30 ꢂC
(+)-d-muricatacin 1513 are shown in Fig. 2. Polyporolide 1 is for 12 h. Aer completion of reaction, the mixture was
assigned the anti-relative stereochemistry for C3, C4 and C5 quenched with water (15 mL) and NaOH solution (30% aq.). It
contiguous protons (Fig. 1).1 Similar relative stereochemistry was then treated with saturated aq. NaCl (20 mL), and the
exists in (+)-mupirocin H 13. However, the chemical shis resulting mixture was stirred vigorously for an additional
values of reported 1 for C3, C4 and C5 protons as shown, 30 min at room temperature. The mixture was then vacuum
completely mis-match with that in 13. But there exists a good ltered through a pad of celite, and the lter cake was washed
match of these protons shis of 13 with that of synthetic 1. A with CH2Cl2 (50 mL). The organic phase was separated, and the
similar correlation can be extended for synthetic 1 with that of aqueous phase was extracted with CH2Cl2 (3 ꢃ 20 mL). The
(ꢀ)-muricatacin 14 for C4 and C5 protons with regards to d combined organic layers were washed with water, brine, dried
values. It can be further extended even to (+)-d-muricatacin 15 (Na2SO4) and concentrated. The residue was puried by silica
for the C5 and C6 protons which are similar to C4 and C5 in gel column chromatography using petroleum ether/EtOAc
polyporolide 1. The 13C NMR data for reported 1 for C3 (70.1), (4 : 1) as eluent to afford 3 (0.248 g, 85%) as colorless oil. [a]2D5
C4 (91.6) and C5 (71.4) do not match with that of synthetic 1 for ¼ ꢀ41.2 (c ¼ 0.7, CHCl3), lit.6 [a]D24 ¼ ꢀ43.0 (c ¼ 0.45, CHCl3). IR
C3 (67.9), C4 (91.6) and C5 (71.4), respectively. Thus, the (CHCl3): nmax ¼ 3424, 2952, 2929, 2859, 1457, 1158, 1109, 1045,
synthetic 1 has the structure as depicted in Fig. 2. It is apparent 865, 704, 668 cmꢀ1. 1H NMR (400 MHz, CDCl3/TMS): d 3.91 (dd,
from this mis-match of data of synthesised 1, that the proposed J ¼ 12.6, 2.4 Hz, 1H), 3.62 (dd, J ¼ 12.5, 4.3 Hz, 1H), 2.97–2.90
structure of polyporolide needs revision.
(m, 2H), 1.71 (br. s, 1H, OH), 1.59–1.53 (m, 2H), 1.48–1.39 (m,
2H), 1.36–1.27 (m, 4H), 0.89 (t, J ¼ 7.1 Hz, 3H) ppm. 13C NMR
(100 MHz, CDCl3): d 61.7, 58.5, 56.02, 31.5, 31.46, 25.6, 22.5,
13.9 ppm.
Conclusions
In conclusion, a stereoselective synthesis of the reported
(2R,3S)-Octane-1,2,3-triol (7). To a solution of epoxy alcohol 3
structure of polyporolide 1 has been achieved in 7–9 steps and (0.5 g, 3.47 mmol) in 1,4-dioxane (10 mL) was added 0.5 N NaOH
12.3–13.5% overall yields. The key steps involve Sharpless (2 mL) at room temperature. The mixture was stirred under
epoxidation and diastereoselective aldol-type acetate anion reux for 48 h, then cooled to room temperature and concen-
addition. Alternatively ring-closing-metathesis, asymmetric trated to a volume of 1.0 mL. The mixture was extracted with
dihydroxylation and trans-lactonizaton also yielded poly- CH2Cl2 (3 ꢃ 10 mL). The combined organic layers were washed
porolide 1. The reported polyporolide 1 had specic rotation with water, brine, dried (Na2SO4) and concentrated. The
value of [a]2D0 ¼ +13.1 (c ¼ 0.2, MeOH),1 while the synthesized reduced was puried by silica gel column chromatography
compound showed [a]2D5 ¼ +4.7 (c ¼ 0.1, MeOH). A comparison using petroleum ether/EtOAc (1 : 1) to give compound 7
25
ꢂ
of the spectral data of synthetic 1 with that of proposed struc- (0.399 g, 71%) as white solid. Mp 95–96 C, [a]D ¼ ꢀ20.9 (c ¼
ture and known similar molecules is conclusive of the need of 0.75, EtOH), lit.14 104–105 ꢂC, [a]D20 ¼ ꢀ21.4 (c ¼ 0.98, EtOH). IR
structure revision for proposed polyporolide.
(CHCl3): nmax ¼ 3398, 3018, 2956, 2932, 2873, 2861, 1466, 1072,
916, 880, 671 cmꢀ1. 1H NMR (400 MHz, acetone-d6): d 3.76–3.71
(m, 2H), 3.67–3.48 (m, 2H), 3.41 (dd, J ¼ 10.4, 6.1 Hz, 1H), 1.68–
Experimental section
General information
Solvents were dried by standard procedures. Thin-layer chro- 21.9, 13.0 ppm. HRMS: m/z calcd for C8H18O3Na [M + Na]+
1.52 (m, 2H), 1.43–1.27 (m, 6H), 0.88 (t, J ¼ 6.8 Hz, 3H) ppm. 13
C
NMR (125 MHz, acetone-d6): d 74.1, 71.9, 63.1, 32.4, 31.3, 24.7,
matography was performed on EM 250 Kieselgel 60 F254 silica 185.1154; found: 185.1151.
gel plates. The spots were visualized by staining with KMnO4 or
by using UV lamp. 1H-NMR and 13C-NMR were recorded on stirred solution of 7 (150 mg, 0.925 mmol) in dry THF (6 mL) at
Varian 400, Bruker AvanceIII 400 and 500 spectrometers and the ꢂC were sequentially added Et3N (0.52 mL, 3.7 mmol,
(2R,3S)-1-(tert-Butyldimethylsilyloxy)octane-2,3-diol (8). To a
0
chemical shis are based on TMS peak at d ¼ 0.00 pm for 4.0 equiv.) and TBSOTf (0.330 mL, 1.437 mmol, 1.55 equiv.). The
proton NMR and CDCl3 peak at d ¼ 77.00 ppm (t) in carbon reaction mixture was stirred at room temperature for 5 min. It
NMR. IR spectra were obtained on Perkin Elmer Spectrum One was then quenched with water (0.2 mL) and the aqueous layer
FT-IR spectrometer. Optical rotations were measured with Jasco extracted with EtOAc (3 ꢃ 15 mL). The combined organic layers
P-2000 digital polarimeter using Sodium D line (589 nm). HRMS were washed with water, brine, dried (Na2SO4) and concen-
were recorded using Micromass: Q-Tof micro (YA-105) spec- trated. The residue was puried by silica gel column chroma-
trometer. Compound 6 was prepared following literature tography using petroleum ether/EtOAc (17 : 3) as eluent to
procedure.5
afford 8 (194.4 mg, 76%) as colorless oil. [a]2D5 ¼ ꢀ5.2 (c ¼ 0.4,
(2S,3S)-2,3-Epoxyoctan-1-ol (3).6 To ame dried molecular CHCl3). IR (CHCl3): nmax ¼ 3305, 2949, 2929, 2857, 1464, 1252,
sieves 4 A (0.7 g) in CH2Cl2 (15 mL) were added (+)-diisopropyl 1095, 1068, 912, 836, 666 cmꢀ1
.
1H NMR (400 MHz, CDCl3/
˚
L-tartrate (95 mg, 0.406 mmol, 0.2 equiv.) and Ti(OiPr)4 TMS): d 3.80–3.75 (m, 2H), 3.74–3.66 (m, 1H), 3.58–3.52 (m, 1H),
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1.9 (br. s, 2H, OH), 1.52–1.25 (m, 8H), 0.92–0.84 (m, 12H), 0.07 (0.05 mL, 0.512 mmol, 2 equiv.) in dry THF was added over
(s, 6H) ppm. 13C NMR (100 MHz, CDCl3): d 73.5, 73.4, 64.1, 33.2, 10 min, and the resulting soln. was stirred for another 15 min.
32.1, 26.1, 25.9, 22.8, 18.4, 14.2, ꢀ5.2, ꢀ5.3 ppm. HRMS: m/z Then, the solution of above aldehyde (50 mg) in THF was added
calcd for C14H32O3SiNa [M + Na]+ 299.2013; found 299.2015.
slowly at ꢀ78 C. The resulting mixture was stirred further for
ꢂ
(2R,3S)-1-(tert-Butyldimethylsilyloxy)-2,3-(isopropylidene- 4 h at the same temp., followed by quenching the reaction with
dioxy) octane (9). To a solution of diol 8 (180 mg, 0.651 mmol) in saturated aq. NH4Cl soln. The aqueous layer was extracted with
CH2Cl2 (15 mL) was added pTsOH$2H2O (4 mg) and 2,2-dime- EtOAc (3 ꢃ 10 mL) and the combined organic layers were
thoxypropane (0.28 mL, 2.28 mmol, 3.5 equiv.). The reaction washed with water, brine, dried (Na2SO4) and concentrated. The
mixture was stirred at room temperature for 4 h and then residue was puried by silica gel column chromatography using
quenched with saturated aq. NaHCO3 (0.5 mL) and stirred for petroleum ether/EtOAc (4 : 1) as eluent to give 10 (40 mg, 54%
additional 15 min. The solution was extracted with CH2Cl2 (3 ꢃ from 2) as colorless oil. [a]2D5 ¼ ꢀ25.9 (c ¼ 0.1, CHCl3). IR
15 mL) and the combined organic layers were washed with (CHCl3): nmax ¼ 3437, 2956, 2931, 2873, 1725, 1463, 1379, 1248,
brine, dried (Na2SO4) and concentrated. The residue was puri- 1165, 1097, 1042, 699 cmꢀ1. 1H NMR (400 MHz, CDCl3/TMS): d
ed by silica gel column chromatography using petroleum 4.21–4.15 (m, 3H), 4.07–4.02 (m, 1H), 3.88 (dd, J ¼ 8.8, 5.7 Hz,
ether/EtOAc (9 : 1) as eluent to afford 9 (169 mg, 82%) as 1H), 2.80 (dd, J ¼ 17.1, 2.5 Hz, 1H), 2.49 (dd, J ¼ 17.1, 9.0 Hz,
colorless oil. [a]D25 ¼ ꢀ3.2 (c ¼ 0.3, CHCl3). IR (CHCl3): nmax
¼
1H), 1.75–1.42 (m, 8H), 1.39 (s, 3H), 1.32 (s, 3H), 1.28 (t, J ¼
2957, 2931, 2859, 1464, 1380, 1364, 1260, 1097, 1046, 912, 839, 7.1 Hz, 3H), 0.89 (t, J ¼ 6.9 Hz, 3H) ppm. 13C NMR (100 MHz,
809, 777, 735, 672 cmꢀ1 1H NMR (400 MHz, CDCl3/TMS): d CDCl3): d 173.5, 107.8, 79.0, 78.1, 66.6, 60.8, 38.4, 31.9, 29.3,
.
4.15–4.10 (m, 1H), 4.08–4.03 (m, 1H), 3.66 (dd, J ¼ 10.2, 7.4 Hz, 28.2, 26.3, 25.6, 22.6, 14.2, 14.0 ppm. HRMS: m/z calcd. for
1H), 3.57 (dd, J ¼ 10.3, 5.0 Hz, 1H), 1.60–1.48 (m, 3H), 1.41 (s,
3H), 1.38–1.25 (m, 5H), 1.33 (s, 3H), 0.91–0.86 (m, 12H), 0.06 (s,
C
15H28O5Na [M + Na]+ 311.1829; found 3111.1821.
(4R,5S)-4-Hydroxy-5-[(S)-1-hydroxyhexyl]dihydrofuran-2(3H)-
3H), 0.057 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): d 107.5, one (1). The ester 10 (30 mg, 0.104 mmol) was dissolved in
77.9, 77.7, 62.1, 31.9, 29.0, 28.3, 26.4, 25.9, 25.6, 22.6, 18.2, 14.0, methanol (10 mL) and 4 N HCl (2 mL) was added and reuxed
ꢀ5.4, ꢀ5.5 ppm. HRMS: m/z calcd for C17H36O3SiNa [M + Na]+ for 8 h. The mixture was then cooled to room temperature and
339.2326; found 339.2327.
quenched with NaHCO3 and ltered. The ltrate was concen-
(2R,3S)-2,3-(Isopropylidenedioxy)octan-1-ol (2). To a solution trated and the residue puried by ash column chromatog-
9 (100 mg, 0.315 mmol) in dry THF (10 mL) was added TBAF raphy using petroleum ether/EtOAc (1 : 1) as eluent to afford 1
(0.48 mL, 0.48 mmol, 1.5 equiv., 1 M solution in THF) at 0 C (16.2 mg, 77%) as colorless oil. [a]2D5 ¼ +4.5 (c ¼ 0.1, MeOH). IR
ꢂ
and the mixture warmed to room temperature over 3 h. It was (CHCl3): nmax ¼ 3428, 2956, 2928, 2858, 1770, 1468, 1378, 1262,
then quenched with water and stirred for 15 min. THF was 1197, 1075, 1056, 1004, 910, 839, 649 cmꢀ1. 1H NMR (500 MHz,
removed under reduced pressure and the aqueous layer CDCl3/TMS): d 4.64 (t, J ¼ 3.4 Hz, 1H), 4.23 (t, J ¼ 3.4 Hz, 1H),
extracted with EtOAc (3 ꢃ 5 mL). The combined organic layers 3.84 (t, J ¼ 4.2 Hz, 1H), 2.94 (dd, J ¼ 18.2, 7.3 Hz, 1H), 2.55 (br. s,
were washed with water, brine, dried (Na2SO4) and concen- 2H, OH), 2.53 (dd, J ¼ 18.2, 4.0 Hz, 1H), 1.62–1.51 (m, 3H), 1.32–
trated. The residue was puried by silica gel column chroma- 1.25 (m, 5H), 0.90 (t, J ¼ 6.5 Hz, 3H) ppm. 13C NMR (100 MHz,
tography using petroleum ether/EtOAc (4 : 1) as eluent to give 2 CDCl3): d ¼ 176.1, 89.8, 71.5, 67.9, 38.5, 32.6, 31.6, 25.2, 22.5,
(55 mg, 86%) as colorless oil. [a]2D5 ¼ 6.2 (c ¼ 0.2, CHCl3). IR 14.00 ppm. HRMS: m/z calcd for C10H19O4 [M + H]+ 203.1278;
(CHCl3): nmax ¼ 3419, 2985, 2955, 2932, 2873, 1460, 1380, 1369, found 203.1279.
1247, 1168, 1102, 1045, 881, 666 cmꢀ1
.
1H NMR (500 MHz,
(S)-Oct-1-en-3-ol (5). To a mixture of triphenylphosphine
CDCl3/TMS): d 4.16–4.11 (m, 2H), 3.62–3.57 (m, 2H), 2.09 (br. s, (1.162 g, 4.43 mmol, 1.5 equiv.), imidazole (0.502 g, 7.38 mmol,
1H, OH), 1.57–1.23 (m, 8H), 1.46 (s, 3H), 1.35 (s, 3H), 0.88 (t, J ¼ 2.5 equiv.) and 2 (0.6 g, 2.95 mmol) in THF (30 mL) was added
7.0 Hz, 3H) ppm. 13C NMR (125 MHz, CDCl3): d 108.0, 77.9, iodine (1.124 g, 4.43 mmol, 1.5 equiv.) portion wise at 0 ꢂC. The
77.01, 61.8, 31.8, 28.8, 28.2, 26.3, 25.5, 22.5, 14.0 ppm. HRMS: resulting solution was stirred for 3 h at room temperature. The
m/z calcd for C11H22O3Na [M + Na]+ 225.1461; found 225.1452. reaction was quenched by adding saturated aq. Na2S2O3 and
Ethyl(3R,4S,5S)-3-hydroxy-4,5-(isopropylidenedioxy)decanoate extracted with EtOAc (3 ꢃ 30 mL). The combined organic layers
(10). To a solution of alcohol 2 (0.052 g, 0.256 mmol) in CH2Cl2 were washed with water, brine, dried (Na2SO4) and concen-
(10 mL) was added Dess–Martin periodinane (0.152 g, trated. The residue was puried by silica gel column chroma-
0.358 mmol, 1.4 equiv.) in one portion and the reaction mixture tography using petroleum ether/EtOAc (9 : 1) as eluent to afford
stirred at room temperature for 3 h. The mixture was then the corresponding iodide (0.862 g, 93%) as colorless oil. This
ltered through a celite pad and the ltrate concentrated under was used immediately in next reaction.
reduced pressure. The residue was puried by silica gel column
To a solution of iodide (0.84 g, 2.68 mmol) in Et2O (10 mL) at
chromatography using petroleum ether/EtOAc (9 : 1) as eluent room temperature was added Zn dust (1.49 g, 22.78 mmol,
to afford the corresponding aldehyde (50 mg) as colorless oil. 8.5 equiv.) and acetic acid (2 mL). The mixture was stirred for
This was immediately used in the next reaction.
4 h and then quenched with 2 N HCl and stirred for 5 min. The
To a solution of iPr2NH (0.08 mL, 0.563 mmol, 2.2 equiv.) in suspension was extracted with Et2O (3 ꢃ 30 mL) and the
dry THF (10 mL) was added nBuLi (1.6 M in THF, 0.34 mL, combined organic layers were washed with water, brine, dried
0.54 mmol, 2.1 equiv.) dropwise at ꢀ78 ꢂC. The reaction mixture (Na2SO4) and concentrated. The residue was puried by silica
was stirred for 30 min at ꢀ78 ꢂC. A solution of ethylacetate gel column chromatography using petroleum ether/CH2Cl2
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(4 : 1) as eluent to afford 5 (0.295 g, 86%) as colorless oil. [a]D25
¼
N KOH (10 mL), brine, dried (Na2SO4) and concentrated. The
+9.2 (c ¼ 0.16, CHCl3), lit.15 [a]D25 ¼ +9.0 (c ¼ 0.4, CHCl3). IR residue was puried by silica gel column chromatography using
(CHCl3): nmax ¼ 3434, 2956, 2932, 2859, 1648, 1464, 1380, 1262, petroleum ether/EtOAc (1 : 1) as an eluent to give 1 (0.156 g,
1092, 1036, 925, 867 cmꢀ1. 1H NMR (400 MHz, CDCl3/TMS): d ¼ 71%) as a colorless oil. [a]D25 ¼ +4.7 (c ¼ 0.1, MeOH). Spectral
5.87 (ddd, J ¼ 17.2, 10.5, 6.4 Hz, 1H), 5.22 (td, J ¼ 17.2, 1.4 Hz, data is same as before.
1H), 5.10 (td, J ¼ 10.4, 1.3 Hz, 1H), 4.13–4.07 (m, 1H), 1.59–1.24
(m, 9H), 0.88 (t, J ¼ 7.2 Hz, 3H) ppm. 13C NMR (100 MHz,
Acknowledgements
CDCl3): d ¼ 141.3, 114.6, 73.3, 37.0, 31.7, 25.0, 22.6, 14.0 ppm.
HRMS: m/z calcd for C8H16OK [M + K]+ 167.0838; found
167.0839.
We thank the Board of Research in Nuclear Sciences (BRNS),
Grant no. 2013/37C/59/BRNS for nancial support. P.H.P
thanks University Grants Commission (UGC), New Delhi for
research fellowship.
(S)-Oct-1-en-3-yl but-3-enoate (12). To a solution of the allylic
alcohol 5 (0.34 g, 2.65 mmol) in CH2Cl2 (20 mL) were added
3-butenoic acid 11 (1.14 g, 13.25 mmol, 5.0 equiv.), DCC
(1.094 g, 5.30 mmol, 2.0 equiv.) and DMAP (33 mg, 0.27 mmol,
10 mol%) at 0 ꢂC. The mixture was warmed to room temperature
and stirred for 6 h. It was then quenched with 2 N HCl. The
suspension was extracted with CH2Cl2 (3 ꢃ 30 mL) and the
combined organic layers were washed with water, brine, dried
(Na2SO4) and concentrated. The residue was puried by silica
gel column chromatography using the petroleum ether/CH2Cl2
Notes and references
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2006, 20, 1145.
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Asymmetry, 2011, 22, 1114; (b) R. A. Fernandes and
A. K. Chowdhury, Eur. J. Org. Chem., 2011, 1106; (c)
R. A. Fernandes, M. B. Halle, A. K. Chowdhury and
A. B. Ingle, Tetrahedron: Asymmetry, 2012, 23, 60; (d)
R. A. Fernandes and P. Kattanguru, Asian J. Org. Chem.,
2013, 2, 74; (e) R. A. Fernandes and M. B. Halle, Asian J.
Org. Chem., 2013, 7, 593; (f) D. A. Chaudhari, P. Kattanguru
and R. A. Fernandes, Tetrahedron: Asymmetry, 2014, 25,
1022; (g) R. A. Fernandes, P. H. Patil and A. K. Chowdhury,
Eur. J. Org. Chem., 2014, 237; (h) R. A. Fernandes and
P. Kattanguru, J. Org. Chem., 2012, 77, 9357.
as eluent to afford 12 (0.364 g, 70%) as colorless oil. [a]D25
¼
ꢀ5.2 (c ¼ 0.2, CHCl3). IR (CHCl3): nmax ¼ 3085, 2956, 2933, 2862,
1741, 1644, 1467, 1426, 1379, 1323, 1252, 1293, 1174, 1094, 991,
923, 886 cmꢀ1. 1H NMR (400 MHz, CDCl3/TMS): d 6.00–5.86 (m,
1H), 5.77 (ddd, J ¼ 17.3, 10.5, 6.5 Hz, 1H), 5.29–5.12 (m, 5H),
3.11 (td, J ¼ 7.0, 1.3 Hz, 2H), 1.70–1.50 (m, 2H), 1.42–1.20 (m,
6H), 0.88 (t, J ¼ 6.3 Hz, 3H) ppm. 13C NMR (100 MHz, CDCl3): d
¼ 170.8, 136.5, 130.4, 118.5, 116.6, 75.1, 39.4, 34.1, 31.5, 24.7,
22.5, 14.0 ppm. HRMS: m/z calcd for C12H20O2Na [M + Na]+
219.1361; found 219.1351.
(S)-6-Pentyl-3,6-dihydro-2H-pyran-2-one (4). To a stirred and
degassed solution of 12 (100 mg, 0.51 mmol) in dry CH2Cl2
(70 mL) was added Grubbs second-generation catalyst (4.3 mg,
0.005 mmol, 1.0 mol%) at room temperature and the mixture
reuxed for 12 h. It was then cooled and ltered through a small
pad of silica gel and the ltrate concentrated. The residue was
puried by silica gel column chromatography using petroleum
ether/EtOAc (6 : 1) as eluent to give 4 (82.3 mg, 96%) as colorless
oil. [a]2D5 ¼ +35.2 (c ¼ 0.24, CHCl3). IR (CHCl3): nmax ¼ 2956,
2932, 2861, 1735, 1467, 1382, 1240, 1165, 1118, 1057, 829, 704
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102, 5974; (b) Y. Gao, R. M. Hanson, J. M. Klunder,
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1996, 35, 448; (b) H. C. Kolb, M. S. VanNieuwenhze and
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1
cmꢀ1. H NMR16 (400 MHz, CDCl3/TMS): d 5.88–5.81 (m, 2H),
4.99–4.96 (m, 1H), 3.07–3.05 (m, 2H), 1.78–1.71 (m, 2H),
13
1.40–1.25 (m, 6H), 0.89 (t, J ¼ 6.9 Hz, 3H) ppm. C NMR16
(100 MHz, CDCl3): d 169.2, 126.6, 121.4, 79.7, 35.6, 31.4, 29.9,
23.9, 22.5, 13.9 ppm.
(4R,5S)-4-Hydroxy-5-[(S)-1-hydroxyhexyl]dihydrofuran-2(3H)-
one (1) from 4. To a mixture of K3Fe(CN)6 (0.942 g, 2.86 mmol,
3.0 equiv.), K2CO3 (0.396 g, 2.86 mmol, 3.0 equiv.), MeSO2NH2
(90.6 mg, 0.952 mmol, 1.0 equiv.), (DHQ)2PHAL (7.6 mg, 0.0096
mmol, 1.0 mol%) and K2OsO4$2H2O (1.4 mg, 0.0038 mmol, 0.4
mol%) were added t-BuOH (3 mL) and water (5 mL). The
mixture was stirred for 5 min and cooled at 0 ꢂC in ice bath. To
the cooled mixture, a solution of the olen 4 (160 mg, 0.952
mmol) in t-BuOH (2 mL) was added. The reaction mixture was
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ꢂ
stirred at 0 C for 24 h and then quenched with solid Na2SO3
and stirred for 30 min. The solution was extracted with EtOAc (3
ꢃ 20 mL) and the combined organic layers were washed with 2
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