Total synthesis of (+)-monocerin via tandem dihydroxylation-SN2 cyclization and a copper mediated tandem cyanation-lactonization approach

Article abstract of DOI:10.1039/c4ob00965g

A simple and novel synthesis of (+)-monocerin was achieved in 15 steps and 15.5% overall yield from 3-buten-1-ol employing hydrolytic kinetic resolution, Julia olefination, intramolecular tandem Sharpless asymmetric dihydroxylation-S_N2 cyclizat

Full text of DOI:10.1039/c4ob00965g

Organic &
Biomolecular Chemistry
View Article Online
View Journal | View Issue
PAPER
Total synthesis of (+)-monocerin via tandem
dihydroxylation-SN2 cyclization and a copper
mediated tandem cyanation–lactonization
approach†
Cite this: Org. Biomol. Chem., 2014,
12, 5973
U. Nookaraju, Eeshwaraiah Begari* and Pradeep Kumar*
Received 9th May 2014,
Accepted 29th May 2014
A simple and novel synthesis of (+)-monocerin was achieved in 15 steps and 15.5% overall yield from
3-buten-1-ol employing hydrolytic kinetic resolution, Julia olefination, intramolecular tandem Sharpless
asymmetric dihydroxylation-SN2 cyclization and a novel copper mediated tandem cyanation–cyclization
as the key steps.
DOI: 10.1039/c4ob00965g
www.rsc.org/obc
Introduction
Natural products make up a significant portion of the current
drug market and they play a crucial role in the discovery of
new drug therapies. Hence the total synthesis of biologically
active natural products is a constant challenge for many scien-
tists working on drug discovery around the globe. Monocerin 1
and its analogues are polyketide natural products1 which are
attractive synthetic targets due to their fascinating architecture
(Fig. 1). Monocerin was first isolated by Aldridge et al. in 1970
from culture filtrates of Helminthosporium monoceras as an
anti-powdery mildew (Erisyphe graminis) of wheat.2 In 1979,
Grove and co-workers noticed monocerin as an insecticidal
constituent of the entomogenous fungus Fusarium larvarum
Fukel.3 Later on, monocerin, dihydroisocoumarins and their
analogues (Fig. 1) were isolated from several other fungal
species3,4 exhibiting a broad spectrum of biological properties
such as antifungal,4a phytotoxic,4b plant pathogenic4c and
insecticidal activities.5
In 2008, Sriubolmas and co-workers identified the antiplas-
modial activity6 of monocerin 1 (IC50 value of 0.68 µM) against
the multidrug-resistant K1 strain of Plasmodium falciparum.
Monocerin and its analogues were proved to be a non specific
toxin and a nonspecific inhibitor of seed germination by inter-
ference with selected stages of cell division cycles.7 Its struc-
ture contains a 4-oxyisochroman-1-one skeleton and a 2,3,5-
trisubstituted tetrahydrofuran, which are fixed with all-cis
stereochemistry.
Fig. 1 Polyketide (1–5) and dihydroisocoumarin (6–9) natural products.
While the first synthesis of monocerin was reported by
Mori et al. in 1989,8 the Simpson group subsequently
described its biomimetic synthetic pathway.9 In recent years
monocerin and its analogues have attracted a great deal of
interest, consequently several syntheses of this molecule were
reported.10 While She et al. reported its synthesis via an intra-
molecular nucleophilic trap of a quinonemethide intermediate
through benzylic oxidation using PIFA,10a Lee and co-workers
described its synthesis through radical cyclization of a vinylic
ether.10b
Herein, we report a simple and efficient synthesis of
(+)-monocerin employing hydrolytic kinetic resolution, Julia–
Kocienski olefination, intramolecular tandem Sharpless asym-
metric dihydroxylation-SN2 cyclization and a novel copper-
mediated tandem cyanation–lactonization of a substituted
bromo benzene derivative as the key steps.
CSIR-National Chemical Laboratory, Division of Organic Chemistry,
Dr. Homi Bhabha Road, Pune, 411008, India. E-mail: e.begari@ncl.res.in;
Fax: +91 20 25902629; Tel: +91 20 25902057
†Electronic supplementary information (ESI) available: Copies of the NMR
spectra (1H & 13C) of all compounds. See DOI: 10.1039/c4ob00965g
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 5973–5980 | 5973

View Article Online
Paper
Organic & Biomolecular Chemistry
Results and discussion
The retrosynthetic analysis of (+)-monocerin 1 is visualized
based on a linear approach as outlined in Scheme 1. We envi-
sioned that the target molecule 1 could be prepared by tandem
cyanation–cyclization of a substituted tetrahydrofuran alcohol
10 which could be derived via tandem Sharpless asymmetric
dihydroxylation-SN2 cyclization of olefin 12. The olefin 12
could be prepared by a Julia–Kocienski olefination reaction
between trimethoxybenzaldehyde and sulfone 13. Compound
13 in turn could be derived from commercially available
3-buten-1-ol via hydrolytic kinetic resolution.
As illustrated in Scheme 2, our synthesis began with the
commercially available 3-buten-1-ol. Upon hydroxy group pro-
tection using PMBCl, followed by oxidation using m-CPBA, this
gave ( )-14, which was subjected to Jacobsen’s HKR11 protocol
using an (S,S)-salen-CoIII(OAc) catalyst to give the enantiopure
epoxide (−)-1412 and diol. The epoxide ring opening12,13 with
ethyl magnesium bromide ((−)-14→15), followed by protection
of the hydroxy group with MOM chloride using diisopropyl-
ethylamine as a base, gave the MOM ether 16 in almost quanti-
tative yield. Subsequent oxidative removal of the 4-methoxy
benzyl group with DDQ afforded the alcohol 17 in excellent
yield.
Next, we sought to synthesize the olefin fragment 12.
Initially we attempted the Horner–Wittig reaction of 3,4,5-tri-
methoxyphenylmethylenephosphonate with aldehyde derived
from 17 under various conditions to obtain 12. For example,
the use of different bases such as NaH (1.5 to 6 equiv.), n-BuLi,
KOtBu and NaHMDS (2 equiv.) etc. for the above transform-
ation was a total failure. Raising the temperature from 0 °C to
rt and reflux temperature in various solvents such as THF or
DMF also did not work.
Hence we modified the strategy and proceeded with the
Julia–Kocienski olefination reaction to obtain the required
olefin 12. Thus the primary alcohol 17 was converted to sulfide
18 under Mitsunobu conditions using 1-phenyl-1H-tetrazole-5-
Scheme 2 Total synthesis of (+)-monocerin 1 and formal synthesis of
its stereoisomer 31.
premetallate conditions at −78 °C to 0 °C. However product
thiol as a nucleophile in the presence of TPP/DIAD. Oxidation formation could not be observed under any of the above con-
ditions. Next we switched over to the Barbier conditions using
of sulfide 18 with ammonium heptamolybdate and H2O2
afforded sulfone 13.14 Having sulfone 13 in hand, we wanted
NaHMDS as a base at −78 °C to 0 °C, however this gave only
to optimize the Julia–Kocienski15 olefination conditions by 10% of the desired product. Notably, increasing the tempera-
ture from −78 °C to rt under Barbier conditions resulted in
improvement of yields up to 30%. Eventually, further raising
the temperature from 0 °C to rt, afforded the desired product
12 in 88% yield (Table 1).
screening various bases such as KHMDS and NaHMDS under
Compound 12 was subjected to MOM deprotection with 6
N HCl to give the alcohol 19 in 98% yield. Now the stage was
set for the synthesis of cis-substituted tetrahydrofuran hydroxyl
compound 11 via intramolecular tandem Sharpless asym-
metric dihydroxylation-SN2 cyclization following Marshall’s
protocol.12a Thus the alcohol 19 was converted into its mesy-
late followed by Sharpless asymmetric dihydroxylation16 using
AD-mix-β in tBuOH–H2O (1 : 1) to afford the inseparable
mixture of key cis and trans-substituted tetrahydrofuran 11 and
20 (93 : 7), respectively, in 95% yield. The formation of a
majority of cis-substituted tetrahydrofuran alcohol could be
Scheme 1 Retrosynthetic route to (+)-monocerin.
5974 | Org. Biomol. Chem., 2014, 12, 5973–5980
This journal is © The Royal Society of Chemistry 2014

View Article Online
Organic & Biomolecular Chemistry
Paper
Table 1 Optimization of Julia–Kocienski olefination reaction conditions
Table 2 Optimization for copper cyanide mediated tandem cyanation–
lactonization
Sl. no.
Reaction conditions
Yield (%)
No reaction
No reaction
No reaction
No reaction
10%c
E : Z
—
1
2
3
4
5
6
7
Premetallatea
KHMDS, THF, −78 °C
Premetallate
KHMDS, THF, −78 °C to 0 °C
Premetallate
NaHMDS, THF, −78 °C to rt
Premetallate
NaHMDS, THF, 0 °C to rt
Barbierb
NaHMDS, THF, −78 °C to 0 °C
Barbier
NaHMDS, THF, −78 °C to rt
Barbier
Equivalents
of CuCN
Sl. No.
Temperature
Yielda (%) (22)
—
1
2
3
4
1
1
2
3
100 °C
150 °C
150 °C
150 °C
0b
—
22%c
46%d
75%
—
E only
E only
E only
a Isolated yield. b Quantitative recovery of the starting material.
c ,d Recovery of most of the starting material. e No cyano product was
observed.
30%c
88%c
NaHMDS, THF, 0 °C to rt
a Base first added to sulfone followed by aldehyde addition. b Base
added to a mixture of sulfone and aldehyde. c Isolated yield.
attributed to the well-established steric preference of the AD-
mix reagents and presumed SN2 nature of the cyclization reac-
tion leading to the inversion of configuration at the reacting
centre. The results obtained are analogous to those reported in
a preliminary communication,12a by Marshall et al. where the
synthesis of cis and trans-2,5-disubstituted and 2,3,5-trisubsti-
tuted tetrahydrofuran was achieved from δ and ε-mesyloxy
α,β-unsaturated esters by a tandem dihydroxylation and in situ
SN2 cyclization sequence. It may be pertinent to mention here
that this protocol is amenable to the other stereoisomers of
monocerin by simply taking the (R)-enantiomer of epoxide 14
and changing the ligand in the dihydroxylation step. Selective
aromatic bromination of 11 & 20 with NBS in CH2Cl2 afforded
the bromobenzene derivatives 10 & 21 in 98% yield. At this
stage the two diastereomers could be separated easily by silica
gel column chromatography.
Scheme 3 Plausible mechanism for copper mediated tandem cyana-
tion–lactonization.
Our next task was to convert bromo compound 10 into the
corresponding cyano using CuCN in DMF17 under reflux temp-
erature conditions followed by acid mediated cyclization18 to
To the best of our knowledge, there have been no reports of
give the desired product 22. Initially the formation of the the synthesis of a 6-membered lactone ring through copper-
desired product 22 was not observed by attempting the reac- mediated tandem cyanation–cyclization of
tion of 10 with CuCN (1.0 equiv.) in DMF at 100 °C and only bromo benzene tetrahydrofuran alcohol.
a substituted
the starting material was recovered (Table 2, entry 1).
Mechanistically, the reaction is expected to proceed
Surprisingly, when the reaction was carried out at 150 °C, via oxidative addition of aryl bromide with copper cyanide
instead of the expected product 23, the cyclized product 22 followed by reductive elimination to give the cyano inter-
was directly obtained, albeit in low yield (Table 2, entry 2). mediate. This, on further coordination with copper as a
This provided incentive for an extensive study to explore the Lewis acid, facilitates the attack of the alcohol group. Sub-
copper-mediated tandem cyanation–lactonization of 10. To sequent protodecupration and hydrolysis eventually lead to the
improve the yield, when 2 equiv. of CuCN was used, we could desired cyclized product 22 (Scheme 3).
isolate compound 22 in moderate yield (Table 2, entry 3).
Finally, selective demethylation of a methoxy group from 22
When the same reaction was carried out with 3 equiv. of CuCN using boron trichloride gave the target molecule monocerin 1
at 150 °C, the desired cyclized product 22 was obtained in 75% in 75% yield. In the same manner, we have also accomplished
yield (Table 2, entry 4).
the formal synthesis of the (S,S,S) and (R,R,R) isomers of
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 5973–5980 | 5975

View Article Online
Paper
Organic & Biomolecular Chemistry
ether–EtOAc (91 : 9) as the eluent provided the PMB protected
1
compound (12.8 g, 96% yield) as a colourless liquid. H NMR
(200 MHz, CDCl3) d 7.36–7.25 (m, 2 H), 6.97–6.85 (m, 2 H),
5.86 (tdd, J = 6.7, 10.3, 17.1 Hz, 1 H), 5.20–5.01 (m, 2 H), 4.48
(s, 2 H), 3.83 (s, 3 H), 3.52 (t, J = 6.8 Hz, 2 H), 2.39 (tq, J = 1.3,
6.7 Hz, 2 H); 13C NMR (125 MHz, CDCl3) d 159.1, 135.3, 130.5,
129.2, 116.3, 113.7, 72.5, 69.3, 55.2, 34.2.
To a stirred solution of the above compound (12.0 g,
62.4 mmol) in CH2Cl2 (200 mL) at 0 °C was added m-CPBA
(50%) (32.31 g, 93.62 mmol). The reaction mixture was stirred
at room temperature for 1 h, quenched by a saturated Na2CO3
solution, extracted with CH2Cl2, washed with sat. NaHCO3 and
brine, dried (Na2SO4), concentrated and purified by silica gel
column chromatography using petroleum ether–EtOAc (9 : 1)
as the eluent to yield the epoxide ( )-14 (11.9 g, 92%) as a
colourless liquid. 1H NMR (200 MHz, CDCl3) d 7.35–7.22
(m, 2 H), 6.96–6.85 (m, 2 H), 4.49 (s, 2 H), 3.83 (s, 3 H),
3.68–3.56 (m, 2 H), 3.15–3.03 (m, 1 H), 2.85–2.76 (m, 1 H), 2.54
(dd, J = 2.8, 5.1 Hz, 1 H), 2.03–1.69 (m, 2 H).
Scheme 4 Formal synthesis of (2R,3aR,9bR)-6,7,8-trimethoxy-2-
propyl-2,3,3a,9b-tetrahydro-5H-furo[3,2-c]isochromen-5-one 30.
(S)-2-(2-((4-Methoxybenzyl)oxy)ethyl)oxirane (−)-14
Epoxide ( )-14 (6 g, 28.83 mmol) and (S,S)-salen-Co(III)-OAc
(95.7 mg, 0.0144 mmol) in isopropyl alcohol (0.285 ml) were
stirred at 0 °C for 5 min, and then distilled water (0.285 ml,
15.84 mmol) was added. After stirring for 24 h, the solution
was concentrated and purified by silica gel column chromato-
graphy using petroleum ether–EtOAc (9 : 1) to afford (−)-14
(2.88 mg, 48%) as a yellow coloured syrupy liquid. Continued
chromatography with petroleum ether–EtOAc (1 : 1) provided
the diol as a brown coloured liquid. [α]2D7: −13.1 (c 1.0, CHCl3)
{lit.19 [α]2D6: −13.9° (c 1.0, CHCl3)}; IR (neat, cm−1): νmax 2997,
2924, 1611, 1511, 1416, 1316, 1243, 1174, 1088, 906, 817, 753,
709; 1H NMR (200 MHz, CDCl3) δ 7.28 (d, J = 8.6 Hz, 2 H), 6.89
(d, J = 8.6 Hz, 2 H), 4.47 (s, 2 H), 3.82 (s, 3 H), 3.67–3.54 (m,
2 H), 3.16–2.96 (m, 1 H), 2.79 (t, J = 4.5 Hz, 1 H), 2.53 (dd, J =
2.7, 4.9 Hz, 1 H), 2.03–1.70 (m, 2 H); 13C NMR (50 MHz,
CDCl3) δ 159.2, 130.3, 129.2, 113.8, 72.7, 66.7, 55.2, 50.1, 47.1,
32.9; HRMS (ESI) for C12H16O3Na (M + Na)+ found 231.0992,
calcd 231.0992.
monocerin 31 & 30, respectively (Schemes 2 and 4). In our
method, the synthesis of target molecule 1 was accomplished
in 15 steps in an overall 15.5% yield. Our synthesis of 1 proved
to be efficient in comparison with literature reports (Mori
et al.8 14 steps, 6.6% yield; She et al.10a 12 steps, 12.25% yield;
Lee et al.10b 10 steps, 7.7% yield; Marsden et al.10c 8 steps,
6.5% yield; Fang et al.10d 11 steps, 5% yield).
Conclusions
In summary, we have developed a novel copper mediated
tandem cyanation–cyclization method for the synthesis of
(+)-monocerin and its stereoisomers. The present method is
applicable for the preparation of polyketide and dihydroiso-
coumarin natural products containing
a lactone moiety
through the intramolecular carbonylative coupling of aryl
halide and alcohol. Our approach is suitable for the large-scale
synthesis of 1 and its analogues. Currently the synthesis of
other analogues of monocerin such as 11-hydroxy monocerin
and 12-hydroxy monocerin is under progress in our laboratory.
(R)-1-((4-Methoxybenzyl)oxy)hexan-3-ol 15
To a stirred solution of epoxide (−)-14 (2.0 g, 9.61 mmol) and
CuI (183 mg, 0.961 mmol) in dry THF (60 mL) was added a
1 M solution of ethyl magnesium bromide in THF (14.4 ml,
14.4 mmol, 1 M solution in THF) dropwise at 0 °C, and this
was stirred for 1 h. The mixture was quenched with a saturated
NH4Cl solution (5 mL). The layers were separated, the aqueous
Experimental section
2-(2-((4-Methoxybenzyl)oxy)ethyl)oxirane ( )-14
To a stirred solution of but-3-en-1-ol (5.0 g, 69.33 mmol) in layer was extracted with EtOAc (3 × 10 mL), the combined
THF (100 mL) was added NaH (4.0 g, 90.14 mmol) at 0 °C and organic extracts were washed with brine (2 × 5 mL), followed
this was stirred well for 20 min at rt. Then PMBCl (11.8 ml, by a 25% NH4OH solution (5 ml) and dried over Na2SO4, then
83.22 mmol) was added to the reaction mixture at 0 °C, fol- evaporated to dryness, and silica gel column chromatographic
lowed by addition of TBAI (2.5 g, 6.9 mmol), and this was purification (petroleum ether–EtOAc, 89 : 11) of the crude
stirred at rt for 3 h. The reaction mixture was quenched with product gave 15 (2.2 g, 96%) as a yellow coloured oil. [α]2D6:
ice water and extracted with EtOAc (3 × 50 mL). The extract was +8.41° (c 0.53, CHCl3); IR (neat, cm−1): νmax 3444, 2956, 1612,
1
washed with brine, dried (Na2SO4) and concentrated. Silica gel 1512, 1245, 1085, 1032, 817, 707; H NMR (200 MHz, CDCl3)
column chromatography of the crude product using petroleum δ 7.32–7.20 (m, 2 H), 6.96–6.83 (m, 2 H), 4.46 (s, 2 H), 3.81
5976 | Org. Biomol. Chem., 2014, 12, 5973–5980
This journal is © The Royal Society of Chemistry 2014

View Article Online
Organic & Biomolecular Chemistry
Paper
(s, 4 H), 3.74–3.57 (m, 2 H), 3.00–2.81 (m, 1 H), 1.80–1.66 (1.33 ml, 6.78 mmol) at 0 °C and this was stirred for
(m, 2 H), 1.55–1.24 (m, 4 H), 1.03–0.81 (m, 3 H); 13C NMR 2 h at room temperature. THF was concentrated and a crude
(50 MHz, CDCl3) δ 143.2, 137.5, 129.5, 127.3, 96.1, 77.6, 76.4, product was purified by silica gel column chromatography
58.3, 54.7, 35.4, 32.4, 25.0, 23.2, 21.5; HRMS (ESI) for using petroleum ether–EtOAc (91 : 9) as the eluent to furnish
C14H22O3Na (M + Na)+ found 261.1461, calcd 261.1461.
18 as a yellow coloured oil (954 mg, 96%); [α]2D6: −14.06°
(c 1.48, CHCl3); IR (neat, cm−1): νmax 2955, 2931, 1596, 1499,
1385, 1032, 915, 759, 711; 1H NMR (200 MHz, CDCl3)
δ 7.64–7.51 (m, 5 H), 4.72–4.60 (m, 2 H), 3.78–3.63 (m, 1 H),
(R)-1-Methoxy-4-(((3-methoxymethoxy)hexyl)oxy)methyl)-
benzene 16
To a solution of alcohol 15 (2.0 g, 8.4 mmol) in dry CH2Cl2 3.61–3.41 (m, 2 H), 3.40–3.35 (m, 3 H), 2.18–1.88 (m, 2 H),
(40 mL) was added diisopropylethylamine (3.12 mL, 1.61–1.25 (m, 4 H), 0.97–0.86 (m, 3 H); 13C NMR (100 MHz,
17.64 mmol) at 0 °C. To this mixture MOM chloride (0.94 ml, CDCl3) δ 154.3, 133.7, 130.0, 129.7, 123.8, 95.6, 76.0, 55.7,
12.6 mmol) was added slowly with further stirring for 2 h at 36.4, 33.8, 29.5, 18.4, 14.1; HRMS (ESI) for C15H22O2N4NaS
room temperature. The reaction mixture was quenched with (M + Na)+ found 345.1353, calcd 345.1356.
the addition of cold water at 0 °C. The two phases were
(R)-5-((3-(Methoxymethoxy)hexyl)sulfonyl)-1-phenyl-
1H-tetrazole 13
separated and the aqueous phase was extracted with EtOAc
(3 × 20 mL). The combined organic layers were washed with
water (3 × 20 mL), brine, dried over Na2SO4 and concentrated To a solution of compound 18 (0.9 g, 2.79 mmol) in absolute
to give crude 16. It was purified by silica gel column chromato- EtOH (10 mL) was added (NH4)6Mo7O24·4H2O (1.72 g,
graphy using petroleum ether–EtOAc (93 : 7) as the eluent 1.39 mmol) followed by addition of H2O2 (1.47 mL, 12.55 mmol)
to furnish 16 as a colourless oil (2.34 g, 99%); [α]2D7: −4.39° at 0 °C and this was stirred for 8 h at room temperature.
(c 1.02, CHCl3); IR (neat, cm−1): νmax 2933, 1512, 1246, 1138, The reaction mixture was quenched with addition of cold
1034, 951, 821, 750, 606; 1H NMR (500 MHz, CDCl3) δ 7.26 (br. s., sat. Na2SO3 solution at 0 °C, then filtered through celite. The
2 H), 6.88 (d, J = 8.2 Hz, 2 H), 4.64 (s, 2 H), 4.44 (s, 2 H), solvent was evaporated and then the residue was extracted
3.81 (s, 3 H), 3.71 (t, J = 5.6 Hz, 1 H), 3.54 (t, J = 6.4 Hz, 2 H), with EtOAc, washed with brine, dried over Na2SO4 and concen-
3.37 (s, 3 H), 1.85–1.75 (m, 2 H), 1.54–1.32 (m, 4 H), 0.92 (t, J = trated under reduced pressure to get the crude product which
7.2 Hz, 3 H); 13C NMR (125 MHz, CDCl3) δ 159.1, 130.5, 129.3, was purified by silica gel column chromatography using
113.7, 95.7, 74.9, 72.6, 66.7, 55.5, 55.3, 37.0, 34.7, 18.4, 14.2; petroleum ether–EtOAc, (90 : 10) as the eluent to furnish 13 as
HRMS (ESI) for C16H26O4Na (M + Na)+ found 305.1723, calcd a light yellow coloured semi-solid (960 mg, 97%); [α]D25: −4.43°
305.1723.
(c 1.0, MeOH) {lit.15c for S isomer [α]D23= +8.60° (c 0.91, CHCl3)};
IR (neat, cm−1): νmax 2958, 2932, 1595, 1339, 1149, 1036, 761,
688; 1H NMR (200 MHz, CDCl3) δ 7.82–7.53 (m, 5 H), 4.71–4.61
(R)-3-(Methoxymethoxy)hexan-1-ol 17
To a solution of PMB ether 16 (2.0 g, 7.08 mmol) in dry (m, 2 H), 3.99–3.69 (m, 3 H), 3.40 (s, 3 H), 2.35–1.97 (m, 2 H),
CH2Cl2–H2O (38 : 2) mL was added DDQ (1.93 g, 8.5 mmol) at 1.52–1.28 (m, 4 H), 0.99–0.89 (m, 3 H); 13C NMR (50 MHz,
0 °C with further stirring for 2 h at room temperature. The CDCl3) δ 133.0, 131.4, 129.7, 125.1, 95.7, 75.2, 55.8, 52.6, 36.3,
reaction mixture was quenched with addition of cold water, 26.6, 18.4, 14.0; HRMS (ESI) for C15H22O4N4NaS (M + Na)+
stirred for 30 min, then sat. NaHCO3 solution was added, found 377.1254, calcd 377.1254.
stirred for 30 min, then filtered through celite. The two phases
were separated and the aqueous phase was extracted with
CH2Cl2 (3 × 15 mL). The combined organic layers were washed
(R,E)-1,2,3-Trimethoxy-5-(4-(methoxymethoxy)hept-1-en-1-yl)-
benzene 12
with sat. NaHCO3 (2 × 15 mL), brine, dried over Na2SO4 and To a mixture of compound 13 (930 mg, 2.62 mmol) and tri-
concentrated to give crude 17. It was purified by silica gel methoxybenzaldehyde (514 mg, 2.62 mmol) in dry THF
column chromatography using petroleum ether–EtOAc (86 : 14) (10 mL) was added NaHMDS (4.64 ml, 1 M in THF, 4.64 mmol)
as the eluent to furnish 17 as a yellow coloured oil (1.12 g, dropwise at 0 °C, and this was stirred at room temperature for
99%). [α]2D7: −58.22° (c 1.08, CHCl3); IR (neat, cm−1): νmax 3 h. The reaction mixture was quenched with addition of sat.
1
3385, 2956, 2933, 1095, 1029, 915; H NMR (500 MHz, CDCl3) NH4Cl solution. The two phases were separated and the
δ 4.70 (d, J = 6.7 Hz, 1 H), 4.66 (d, J = 7.0 Hz, 1 H), 3.86–3.70 aqueous phase was extracted with EtOAc (3 × 15 mL). The
(m, 3 H), 3.41 (s, 3 H), 2.15–1.91 (m, 1 H), 1.86–1.79 (m, 1 H), combined organic layers were washed with brine, dried over
1.73–1.65 (m, 1 H), 1.62–1.55 (m, 1 H), 1.53–1.45 (m, 1 H), Na2SO4 and concentrated to give crude 12. It was purified by
1.41–1.32 (m, 2 H), 0.93 (t, J = 7.2 Hz, 3 H); 13C NMR (125 MHz, silica gel column chromatography using petroleum ether–
CDCl3) δ 95.9, 76.4, 59.9, 55.8, 36.8, 36.5, 18.5, 14.2; HRMS (ESI) EtOAc (90 : 10) as the eluent to furnish 12 as a colourless oil
for C8H18O3Na (M + Na)+ found 185.1148, calcd 185.1148.
(749 mg, 88%, E only); [α]D26: +18.46° (c 1.31, CHCl3); IR (neat,
cm−1): νmax 2956, 2930, 1581, 1506, 1416, 1327, 1150, 1124,
(R)-5-((3-(Methoxymethoxy)hexyl)thio)-1-phenyl-1H-tetrazole 18
1
1006, 966, 838, 779; H NMR (500 MHz, CDCl3) δ 6.58 (s, 2 H),
To the solution of resulting alcohol 17 (0.5 g, 3.08 mmol) in 6.36 (d, J = 15.6 Hz, 1 H), 6.24–6.08 (m, 1 H), 4.76–4.66 (m,
dry THF (5 mL) were added PPh3 (1.78 g, 6.78 mmol), 2 H), 3.91–3.83 (m, 9 H), 3.74–3.66 (m, 1 H), 3.40 (s, 3 H),
1-phenyl-1H-tetrazole-5-thiol (0.824 g, 4.62 mmol) and DIAD 2.53–2.37 (m, 2 H), 1.58–1.35 (m, 4 H), 1.01–0.91 (m, 3 H);
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 5973–5980 | 5977

View Article Online
Paper
Organic & Biomolecular Chemistry
13C NMR (125 MHz, CDCl3) δ 153.2, 137.3, 133.3, 132.0, 126.1, 38.3, 19.4, 19.1, 14.1; HRMS (ESI) for C16H24O5Na (M + Na)+
103.0, 95.4, 60.9, 56.0, 55.5, 38.0, 36.6, 18.7, 14.1; HRMS (ESI) found 319.1514, calcd 319.1516.
for C18H28O5Na (M + Na)+ found 347.1826, calcd 347.1829.
(2R,3R,5S)-2-(2-Bromo-3,4,5-trimethoxyphenyl)-
(R,E)-1-(3,4,5-Trimethoxyphenyl)hept-1-en-4-ol 19
5-propyltetrahydrofuran-3-ol 10
To a solution of compound 12 (700 mg, 2.15 mmol) in metha- To a solution of alcohol 11 (100 mg, 0.337 mmol) in CH2Cl2
nol (14 ml), was added 6 N HCl (14 ml) drop wise at rt and stir- (3 mL) was added NBS (66 mg, 0.371 mmol) and the mixture
ring was continued for 2 h (the reaction was monitored by was stirred at 25 °C for 10 min. After the reaction was complete
TLC). The reaction was quenched using sat. NaHCO3 solution. (the reaction was monitored by TLC), it was quenched with sat.
The two phases were separated and the aqueous phase was Na2S2O3 (3 mL) and extracted with CH2Cl2 (3 × 4 mL), washed
extracted with EtOAc (3 × 10 mL). The combined organic layers with water and the combined organic phases were dried over
were washed with brine, dried over Na2SO4 and concentrated Na2SO4 and concentrated to give the crude bromo compound,
to give crude 19. This was purified by silica gel column which was then purified by column chromatography over silica
chromatography using petroleum ether–EtOAc, (85 : 15) as the gel using petroleum ether–EtOAc (90 : 10) to give brominated
eluent to furnish 19 as a white solid (592 mg, 98%); mp.: alcohol 10 (124 mg, 98%) as a colourless oil. It contains
70–71 °C; [α]2D7: −11.27 (c 1.8, CHCl3); IR (neat, cm−1): νmax 8.7 mg of the other diastereomer 23; [α]D28: −55° (c 2.2, CHCl3);
3412, 2955, 2929, 1580, 1453, 1237, 1150, 1006, 966, 838; IR (neat, cm−1): νmax 2935, 2866, 1569, 1481, 1428, 1166, 1012,
1H NMR (400 MHz, CDCl3) δ 6.60 (s, 2 H), 6.41 (d, J = 15.7 Hz, 812, 773; 1H NMR (400 MHz, CDCl3) δ 7.07 (s, 1 H), 4.99 (d, J =
1 H), 6.17 (td, J = 7.5, 15.4 Hz, 1 H), 3.90–3.81 (m, 9 H), 4.1 Hz, 1 H), 4.76–4.69 (m, 1 H), 4.02 (td, J = 6.9, 13.7 Hz, 1 H),
3.79–3.72 (m, 1 H), 2.53–2.39 (m, 1 H), 2.38–2.24 (m, 1 H), 3.91–3.85 (m, 9 H), 2.50 (td, J = 6.8, 14.3 Hz, 1 H), 1.90–1.81
1.68–1.62 (m, 1 H), 1.54–1.37 (m, 4 H), 0.96 (t, J = 6.6 Hz, 3 H); (m, 1 H), 1.76–1.62 (m, 3 H), 1.56–1.41 (m, 2 H), 0.99 (t, J =
13C NMR (100 MHz, CDCl3) δ 153.0, 137.2, 132.7, 132.5, 125.6, 7.3 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 152.8, 150.5, 142.4,
102.8, 70.6, 60.6, 55.7, 40.7, 38.8, 18.6, 13.7; HRMS (ESI) for 132.1, 108.1, 107.4, 84.3, 77.7, 71.8, 61.0, 56.0, 40.5, 38.3, 19.4,
C16H24O4Na (M + Na)+ found 303.1566, calcd 303.1567.
14.2; HRMS (ESI) for C16H23O5BrNa (M + Na)+ found 397.0618,
calcd 397.0621.
(2R,3R,5S)-5-Propyl-2-(3,4,5-trimethoxyphenyl)tetrahydrofuran 11
(2S,3aR,9bR)-6,7,8-Trimethoxy-2-propyl-2,3,3a,9b-tetrahydro-
5H-furo[3,2-c]isochromen-5-one 22
To a solution of compound 19 (200 mg, 0.713 mmol) in dry
CH2Cl2 was added triethylamine (0.4 ml, 2.84 mmol) at 0 °C.
To this mixture mesyl chloride (0.11 ml, 1.42 mmol) was Bromo alcohol 10 (100 mg, 0.267 mmol) was taken in dry DMF
added slowly with further stirring for 2 h at room temperature. (1.0 mL) and CuCN (71 mg, 0.802 mmol) was added to it. The
The reaction mixture was quenched with addition of cold entire solution was refluxed under N2 for 12 h (monitored by
water at 0 °C. The two phases were separated and the aqueous TLC). The reaction mixture was then cooled to room tempera-
phase was extracted with EtOAc (3 × 8 mL). The combined ture, and diluted with water (3 mL) and EtOAc (5 mL). The
organic layers were washed with water (3 × 8 mL), brine, dried organic layer was separated and the aqueous layer was
over Na2SO4 and concentrated to give crude mesylate.
extracted with EtOAc (3 × 5 mL). The combined organic
To a solution of crude mesylate in tBuOH–H2O (1 : 1, extracts were washed with brine and dried over anhyd. Na2SO4
12 mL) were added AD-mix-β (357 mg, 1.4 mg mmol−1) and and concentrated under reduced pressure to give a crude
methanesulfonamide (25.5 mg, 100 mg mmol−1) at 0 °C and product which was purified by column chromatography using
the reaction mixture was allowed to stir for 24 h at 0 °C temp- the eluent dichloromethane–EtOAc (95 : 5) to give cyclized
erature. The reaction was quenched by addition of Na2SO3 product 22 (64 mg, 75%) as a colourless oil; [α]2D7: +23.2°
(360 mg, 1.48 mg mmol−1) and stirred for 1 h at room temp- (c 0.53, CHCl3) {(lit.8 [α]2D1 = +22.8° (c 2.76, CHCl3)}; IR (neat,
erature until it became colourless. EtOAc was used for extrac- cm−1): νmax 2923, 2853, 1717, 1592, 1461, 1366, 1256, 1110,
tion and the organic layer was washed with brine, dried over 1009, 844, 754; 1H NMR (400 MHz, CDCl3) δ 6.79 (s, 1 H),
Na2SO4 and concentrated under reduced pressure to get the 5.01–4.92 (m, 1 H), 4.52 (d, J = 2.7 Hz, 1 H), 4.19–4.10 (m, 1 H),
crude product which was purified by silica gel column chrom- 3.97 (s, 3 H), 3.95 (s, 3 H), 3.89 (s, 3 H), 2.52 (ddd, J = 5.7, 8.6,
atography using petroleum ether–EtOAc, (80 : 20) as the eluent 14.2 Hz, 1 H), 2.16 (dd, J = 5.4, 14.2 Hz, 1 H), 1.77–1.68 (m,
to furnish 11 as a colourless oil (200 mg, 95%), which contains 1 H), 1.64–1.56 (m, 1 H), 1.48–1.34 (m, 2 H), 0.91 (t, J = 7.3 Hz,
7% of the other diastereomer 20 (inseparable) confirmed by 3 H); 13C NMR (100 MHz, CDCl3) δ 159.9, 157.9, 156.5, 144.3,
1H NMR spectroscopy; [α]D28: −51.35° (c 1.85, CHCl3); IR (neat, 132.5, 111.2, 108.1, 79.5, 79.0, 75.1, 61.8, 61.1, 56.2, 39.0, 38.1,
cm−1): νmax 3470, 2955, 2940, 1590, 1418, 1232, 1125, 920, 781; 19.2, 13.9; HRMS (ESI) for C17H23O6 (M + H)+ found 323.1483,
1H NMR (400 MHz, CDCl3) δ 6.63 (s, 2 H), 4.75 (d, J = 3.7 Hz, calcd 323.1489.
1 H), 4.40–4.33 (m, 1 H), 4.09–3.99 (m, 1 H), 3.87 (s, 6 H), 3.84
(2S,3aR,9bR)-6-Hydroxy-7,8-dimethoxy-2-propyl-2,3,3a,9b-
(s, 3 H), 2.49–2.39 (m, 1 H), 1.90–1.81 (m, 1 H), 1.80–1.73
tetrahydro-5H-furo[3,2-c]isochromen-5-one 1
(m, 1 H), 1.70–1.40 (m, 4 H), 0.99 (t, J = 7.2 Hz, 3 H); 13C NMR
(100 MHz, CDCl3) δ 153.4, 137.4, 132.4, 103.7, 103.4, 84.9, To a solution of lactone 22 (48 mg, 0.148 mmol) in dry CH2Cl2
84.3, 78.6, 78.1, 77.2, 74.6, 73.9, 60.8, 56.1, 40.7, 40.2, 38.5, (1 mL) was added BCl3 (1.0 M, 0.163 mL, 0.163 mmol) at
5978 | Org. Biomol. Chem., 2014, 12, 5973–5980
This journal is © The Royal Society of Chemistry 2014

View Article Online
Organic & Biomolecular Chemistry
Paper
−10 °C under argon. The mixture was stirred at −5 °C for 1 h was subjected to tandem Sharpless asymmetric dihydroxyla-
and quenched with saturated aqueous NaHCO3 (1 mL), The tion-SN2 cyclization to give 26 as a colourless oil (40 mg, 95%),
mixture was extracted with CH2Cl2 (3 × 4 mL), and the organic which contains 12% of the other diastereomer 27 (inseparable)
layer was washed with brine, dried over anhydrous Na2SO4, confirmed by 1H NMR spectroscopy. 1H NMR (200 MHz,
concentrated in vacuum and purified by column chromato- CDCl3) δ 0.92–1.05 (m, 3 H) 1.36–1.61 (m, 4 H) 1.79–1.90 (m,
graphy using the eluent petroleum ether–EtOAc (60 : 40) to give 1 H) 2.27 (dd, J = 13.07, 5.75 Hz, 1 H) 3.84 (s, 3 H) 3.87 (s, 6 H)
(+)-monocerin 1 (11.3 mg, 75% yield, brsm) as a colourless oil; 4.35–4.55 (m, 2 H) 5.00 (d, J = 3.03 Hz, 1 H), 6.60 (s, 2 H).
[α]D26 = +53° (c 1, CHCl3) {(lit.2 [α]D25 = +53° (c 1, CHCl3)}; IR
(2R,3R,5R)-2-(2-Bromo-3,4,5-trimethoxyphenyl)-
5-propyltetrahydrofuran-3-ol 28
(neat, cm−1): νmax 2956, 2924, 1663, 1520, 1456, 1274, 1119,
1013, 759; H NMR (400 MHz, CDCl3) δ 11.29 (s, 1 H), 6.60 (s,
1
1 H), 5.06 (dd, J = 3.1, 5.3 Hz, 1 H), 4.55 (d, J = 3.2 Hz, 1 H), The same procedure was followed as described for the prepa-
4.17–4.08 (m, 1 H), 3.96 (s, 3 H), 3.91 (s, 3 H), 2.60 (ddd, J = ration of compound 10. Bromination of alcohol 26 & 27
6.4, 8.4, 14.5 Hz, 1 H), 2.17 (dd, J = 6.0, 14.5 Hz, 1 H), (20 mg, 0.202 mmol) yielded the brominated alcohol 28
1.74–1.67 (m, 1 H), 1.63–1.59 (m, 1 H), 1.45–1.35 (m, 2 H), 0.93 (22 mg, 98%) as a colourless oil. It contains 3 mg of the other
(t, J = 7.3 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 167.8, 158.7, diastereomer 29. [α]D25: −43.54° (c 2.6, CHCl3); 1H NMR
156.3, 137.3, 131.1, 104.3, 102.0, 81.2, 78.7, 74.5, 60.7, 56.2, (500 MHz, CDCl3) δ 7.02 (s, 1 H), 5.25 (d, J = 3.1 Hz, 1 H), 4.77
39.0, 38.0, 19.1, 14.0; HRMS (ESI) for C16H21O6 (M + H)+ found (t, J = 3.2 Hz, 1 H), 4.51–4.45 (m, 1 H), 3.90–3.87 (m, 9 H), 2.23
309.1331, calcd 309.1333.
(dd, J = 5.5, 13.1 Hz, 1 H), 1.91–1.85 (m, 1 H), 1.77–1.70
(m, 1 H), 1.53–1.38 (m, 3 H), 0.98 (t, J = 7.2 Hz, 3 H); 13C NMR
(125 MHz, CDCl3) δ 152.9, 150.6, 142.4, 132.5, 107.7, 107.5,
(S,E)-1-(3,4,5-Trimethoxyphenyl)hept-1-en-4-yl-4-nitrobenzoate 24
To a solution of alcohol 19 (0.2 g, 0.713 mmol) in dry THF 83.7, 78.4, 72.4, 61.0, 56.1, 40.8, 38.1, 19.2, 14.1.
(5 mL) were added PPh3 (0.393 g, 1.49 mmol), p-nitrobenzoic
(2R,3aR,9bR)-6,7,8-Trimethoxy-2-propyl-2,3,3a,9b-tetrahydro-
5H-furo[3,2-c]isochromen-5-one 30
acid (PNBA) (0.143 g, 0.856 mmol) and diisopropylazodi-
carboxylate (DIAD) (0.29 ml, 1.49 mmol) at 0 °C and this
was stirred for 1 h at room temperature. THF was concen- The same procedure was followed as described for the
trated and the crude product was purified by silica gel column preparation of compound 22. Bromo alcohol 28 (10 mg,
chromatography using petroleum ether–EtOAc, (94 : 6) as the 0.026 mmol) yielded cyclized product 30 (6.4 mg, 75%) as a
eluent to furnish 24 as a yellow coloured oil (297 mg, 97%). colourless oil. [α]2D8: +11.34° (c 0.45, CHCl3); 1H NMR
[α]2D7: +39.8° (c 1.03, CHCl3); IR (neat, cm−1): νmax 2959, 2936, (400 MHz, CDCl3) δ 0.96 (t, J = 7.21 Hz, 3 H), 1.48–1.59
1718, 1581, 1505, 1416, 1270, 1184, 1011, 964, 872, 694; (m, 2 H), 1.71–1.76 (m, 2 H), 1.94 (ddd, J = 13.63, 9.60, 3.91 Hz,
1H NMR (400 MHz, CDCl3) δ 8.30–8.26 (m, J = 8.7 Hz, 2 H), 1 H), 2.60 (dd, J = 13.69, 5.87 Hz, 1 H), 3.89 (s, 3 H), 3.97
8.23–8.18 (m, J = 8.7 Hz, 2 H), 6.53 (s, 2 H), 6.39 (d, J = 15.6 Hz, (s, 3 H), 3.96 (s, 3 H) 4.38–4.47 (m, 1 H), 4.76 (d, J = 2.69 Hz, 1 H),
1 H), 6.15–6.06 (m, 1 H), 5.32–5.24 (m, 1 H), 3.88–3.83 5.04 (t, J = 3.06 Hz, 1 H), 6.77 (s, 1 H); 13C NMR (100 MHz,
(m, 9 H), 2.62 (t, J = 6.6 Hz, 2 H), 1.82–1.71 (m, 2 H), 1.53–1.40 CDCl3) δ 160.2, 158.1, 156.6, 144.2, 133.4, 108.0, 80.2, 79.5,
(m, 2 H), 0.97 (t, J = 7.3 Hz, 3 H); 13C NMR (100 MHz, CDCl3) 73.9, 61.8, 61.2, 56.2, 40.2, 38.3, 19.2, 14.0; HRMS (ESI) for
δ 164.4, 153.3, 150.5, 137.7, 136.0, 133.1, 132.9, 130.6, C17H23O6 (M + H)+ found 323.1484, calcd 323.1489.
124.4, 123.5, 103.2, 75.4, 60.9, 56.1, 37.9, 35.8, 18.7, 13.9;
(2S,3S,5S)-2-(2-Bromo-3,4,5-trimethoxyphenyl)-
5-propyltetrahydrofuran-3-ol 21
HRMS (ESI) for C23H27O7NNa (M + Na)+ found 452.1676, calcd
452.1680.
Compound 21 was obtained as a by product in the preparation
(S,E)-1-(3,4,5-Trimethoxyphenyl)hept-1-en-4-ol 25
of compound 10. [α]D27: +39.58° (c 0.92, CHCl3); 1H NMR
To a solution of ester 24 (0.25 g, 0.582 mmol) in THF– (400 MHz, CDCl3) δ 7.03 (s, 1 H), 5.26 (d, J = 3.2 Hz, 1 H), 4.78
MeOH–H2O (3 : 2 : 1) (6 mL) was added LiOH·H2O (0.029 g, (t, J = 3.7 Hz, 1 H), 4.52–4.44 (m, 1 H), 3.91–3.88 (m, 9 H), 2.25
0.699 mmol) at rt and this was stirred for 1 h at room (dd, J = 5.5, 13.3 Hz, 1 H), 1.93–1.85 (m, 1 H), 1.78–1.71 (m,
temperature. Solvent was concentrated and to the residue was 1 H), 1.54–1.44 (m, 3 H), 1.01–0.97 (m, 3 H); 13C NMR
added sat. NaHCO3 (5 ml) and extracted with EtOAc (3 × 5 ml). (100 MHz, CDCl3) δ 152.9, 150.6, 142.4, 132.5, 107.8, 107.5,
The organic layer was washed with brine, dried over anhydrous 83.8, 78.5, 72.4, 61.0, 56.1, 40.8, 38.1, 19.2, 14.1.
Na2SO4 and concentrated in vacuum. Purification by column
(2S,3aS,9bS)-6,7,8-Trimethoxy-2-propyl-2,3,3a,9b-tetrahydro-
chromatography using an eluent petroleum ether–EtOAc
5H-furo[3,2-c]isochromen-5-one 31
(85 : 15) gave 25 (153 mg, 94% yield) as a colourless oil. [α]2D7:
+11.16° (c 1.8, CHCl3).
The same procedure was followed as described for the
preparation of compound 22. Bromo alcohol 21 (6 mg,
0.0801 mmol) yielded cyclized product 31 (3.8 mg, 75%, brsm)
as a colourless oil. [α]2D7: −10.5° (c 0.2, CHCl3); 1H NMR
(2R,3R,5R)-5-Propyl-2-(3,4,5-trimethoxyphenyl)-
tetrahydrofuran-3-ol 26
The same procedure was followed as described for the prepa- (500 MHz, CDCl3) δ 0.94–0.97 (m, 3 H) 1.49–1.57 (m, 2 H)
ration of compound 11. Compound 25 (40 mg, 0.142 mmol) 1.67–1.75 (m, 2 H) 1.94 (ddd, J = 13.66, 9.69, 4.12 Hz, 1 H) 2.59
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 5973–5980 | 5979

View Article Online
Paper
Organic & Biomolecular Chemistry
(dd, J = 13.43, 5.80 Hz, 1 H) 3.89 (s, 3 H) 3.97 (d, J = 4.27 Hz, 7
H) 4.39–4.46 (m, 1 H) 4.76 (d, J = 2.75 Hz, 1 H) 5.04 (t, J =
9 M. P. Dillon, T. J. Simpson and J. B. Sweeney, Tetrahedron
Lett., 1992, 33, 7569–7572.
2.90 Hz, 1 H) 6.78 (s, 1 H); 13C NMR (125 MHz, CDCl3) δ 160.2, 10 (a) B. Fang, X. Xie, C. Zhao, P. Jing, H. Li, Z. Wang, J. Gu
158.1, 156.5, 144.1, 133.4, 108.0, 80.2, 79.5, 73.9, 61.8, 61.2,
56.2, 40.1, 38.3, 19.2, 14.1.
and X. She, J. Org. Chem., 2013, 78, 6338–6343;
(b) H. K. Kwon, Y. E. Lee and E. Lee, Org. Lett., 2008, 10,
2995–2996; (c) J. H. Cassidy, C. N. Farthing, S. P. Marsden,
A. Pedersen, M. Slater and G. Stemp, Org. Biomol. Chem.,
2006, 4, 4118–4126; (d) B. Fang, X. Xie, H. Li, P. Jing, J. Gu
and X. She, Tetrahedron Lett., 2013, 54, 6349–6351;
(e) M. Fujita, K. Mori, M. Shimogaki and T. Sugimura, Org.
Lett., 2012, 14, 1294–1297.
Acknowledgements
E.B. thanks DST New Delhi for the INSPIRE Faculty fellowship
(IFA12-CH-29). U.N.R. thanks UGC, New Delhi for a research
fellowship. The authors thank CSIR, New Delhi for financial 11 (a) M. Tokunaga, J. F. Larrow, F. Kakiuchi and
support as part of XII Five year plan under the title ORIGIN
(CSC0108).
E. N. Jacobsen, Science, 1997, 277, 936; (b) L. P. C. Nielsen,
C. P. Stevenson, D. G. Blackmond and E. N. Jacobsen,
J. Am. Chem. Soc., 2004, 126, 1360–1362.
12 (a) J. A. Marshall and J. J. Sabatini, Org. Lett., 2005, 7,
4819–4822; (b) J. A. Marshall, G. Schaaf and A. Nolting, Org.
Lett., 2005, 7, 5331–5333.
Notes and references
1 L. C. Axford, T. J. Simpson and C. L. Willis, Angew. Chem., 13 D. K. Mohapatra, D. P. Reddy, U. Dash and J. S. Yadav,
Int. Ed., 2004, 43, 727–730. Tetrahedron Lett., 2011, 52, 151–154.
2 D. C. Aldridge and W. B. Turner, J. Chem. Soc., C, 1970, 14 (a) J. D. Panarese and S. P. Waters, Org. Lett., 2009, 11,
2598–2600.
5086–5088; (b) G. Li, R. P. Hsung, B. W. Slafer and
I. K. Sagamanova, Org. Lett., 2008, 10, 4991–4994.
3 J. F. Grove and M. J. Pople, J. Chem. Soc., Perkin Trans. 1,
1979, 2048–2051.
4 (a) F. E. Scott, T. J. Simpson, L. A. Trimble and
J. C. Vederas, J. Chem. Soc., Chem. Commun., 1984, 756–758;
(b) F. Cuq, M. Petitprez, S. Herrmann-Gorline, A. Klaebe
and M. Rossignol, Phytochemistry, 1993, 34, 1265–1270;
15 (a) P. R. Blakemore, J. Chem. Soc., Perkin Trans. 1, 2002,
2563–2585; (b) J. Liu, K. Xu, J. He, L. Zhang, X. Pan and
X. She, J. Org. Chem., 2009, 74, 5063–5066; (c) D. A. Evans,
V. J. Cee, T. E. Smith, D. M. Fitch and P. S. Cho, Angew.
Chem., Int. Ed., 2000, 39, 2533–2536.
(c) C. H. Lim, Agric. Chem. Biotechnol. (Engl. Ed.), 1999, 42, 16 (a) K. B. Sharpless, W. Amberg, Y. L. Bennani,
45–47; (d) W. Zhang, K. Krohn, S. Draeger and B. Schulz,
J. Nat. Prod., 2008, 71, 1078–1081; (e) N. El Aouad,
G. Pérez-Moreno, P. Sánchez, J. Cantizani, F. J. Ortiz-López,
J. Martín, V. González-Menéndez, L. M. Ruiz-Pérez,
G. A. Crispino, J. Hartung, K. S. Jeong, H. L. Kwong,
K. Morikawa and Z. M. Wang, J. Org. Chem., 1992, 57,
2768–2771; (b) H. C. Kolb, M. S. Vannieuwenhze and
K. B. Sharpless, Chem. Rev., 1994, 94, 2483–2547.
D. González-Pacanowska, F. Vicente, G. Bills and F. Reyes, 17 (a) K. W. Rosenmund and E. Struck, Chem. Ber., 1919, 52,
J. Nat. Prod., 2012, 75, 1228–1230; (f) R. Haritakun,
M. Sappan, R. Suvannakad, K. Tasanathai and M. Isaka,
J. Nat. Prod., 2009, 73, 75–78.
1749; (b) J. v. Braun and G. Manz, Liebigs Ann. Chem., 1931,
488, 111–126; (c) J. Zanon, A. Klapars and S. L. Buchwald,
J. Am. Chem. Soc., 2003, 125, 2890–2891.
5 J. F. Grove and M. Pople, Mycopathologia, 1981, 76, 65–67.
6 R. Sappapan, D. Sommit, N. Ngamrojanavanich,
S. Pengpreecha, S. Wiyakrutta, N. Sriubolmas and K. Pudhom,
J. Nat. Prod., 2008, 71, 1657–1659.
18 (a) J. Mangas-Sanchez, E. Busto, V. Gotor-Fernandez and
V. Gotor, Catal. Sci. Technol., 2012, 2, 1590–1595;
(b) J. Mangas-Sánchez, E. Busto, V. Gotor and V. Gotor-
Fernández, Org. Lett., 2013, 15, 3872–3875.
7 F. Cuq, S. C. Brown, M. Petitprez and G. Alibert, Plant Cell 19 (a) S. Roy and C. D. Spilling, Org. Lett., 2010, 12, 5326–
Rep., 1995, 15, 138–142.
8 K. Mori and H. Takaishi, Tetrahedron, 1989, 45, 1639–1646.
5329; (b) F. Glaus and K.-H. Altmann, Angew. Chem.,
Int. Ed., 2012, 51, 3405–3409.
5980 | Org. Biomol. Chem., 2014, 12, 5973–5980
This journal is © The Royal Society of Chemistry 2014