A versatile, RCM based approach to eudesmane and dihydroagarofuran sesquiterpenoids from (-)-carvone: A formal synthesis of (-)-isocelorbicol

Article abstract of DOI:10.1016/j.tet.2015.01.039

An enantiospecific and diversity oriented approach to a range of functionalized eudesmane, nor-, iso-, and dihydroagarofuran frameworks from (-)-carvone is delineated. The cornerstone of this approach is the installation of the quaternary carbon center through reductive opening of the carvone epoxide and setting-up of RCM reaction to generate the bicyclic eudesmane framework. Various options like carbocation mediated oxycyclization and intramolecular hydroxy directed epoxide opening have been explored for the construction of the bridged tetrahydrofuran moiety. Among the several eudesmane and dihydroagarofurans accessed during the present study, one has been previously elaborated to isocelorbicol, thus constituting its formal synthesis.

Full text of DOI:10.1016/j.tet.2015.01.039

Tetrahedron 71 (2015) 1718e1731
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A versatile, RCM based approach to eudesmane and
dihydroagarofuran sesquiterpenoids from (ꢀ)-carvone: a formal
synthesis of (ꢀ)-isocelorbicol
,b,
R. Senthil Kumaran a, Goverdhan Mehta a
*
a Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
b School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An enantiospecific and diversity oriented approach to a range of functionalized eudesmane, nor-, iso-,
and dihydroagarofuran frameworks from (ꢀ)-carvone is delineated. The cornerstone of this approach is
the installation of the quaternary carbon center through reductive opening of the carvone epoxide and
setting-up of RCM reaction to generate the bicyclic eudesmane framework. Various options like carbo-
cation mediated oxycyclization and intramolecular hydroxy directed epoxide opening have been ex-
plored for the construction of the bridged tetrahydrofuran moiety. Among the several eudesmane and
dihydroagarofurans accessed during the present study, one has been previously elaborated to iso-
celorbicol, thus constituting its formal synthesis.
Received 1 January 2015
Accepted 19 January 2015
Available online 31 January 2015
This manuscript is dedicated to the memory
of (late) Professor A. Srikrishna, in appreci-
ation of his extensive and pioneering work
on carvone chemistry
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Sesquiterpenoids
Ring closure metathesis
Oxycyclization
Epoxidation
Natural products synthesis
1. Introduction
Among natural products, sesquiterpenoids have aroused con-
siderable interest and drawn sustained attention as they embody
impressive architectural diversity, replete with variegated func-
tionalities, stereochemical intricacies, and biological activities.
These attributes continue to project sesquiterpenoids as exciting
and challenging synthetic objectives for the organic chemists.1
Among the sesquiterpenoids, eudesmane group based on a bi-
cyclic decalin framework 1 constitute a large, widely occurring and
growing family. These eudesmanoid natural products display var-
ied levels of unsaturation, oxyfunctionalization, and patterns of
stereo-disposition on their compact bicyclic framework. It is esti-
mated that over 1000 eudesmanes based natural products are
known, many of them originating from plants mentioned in tra-
ditional medicine and therefore it is hardly surprising that several
eudesmanes have been found to be biologically active.2 Among the
Fig. 1. Representative eudesmane sesquiterpenoids.
An interesting subclass among eudesmanes is of dihydroagar-
ofurans based on the tricyclic frame 5 comprising of A and B rings of
eudesmane in the form of an axially dimethylated trans-decalin
with a 1,3-bridged tetrahydrofuran as C ring.3,4 While simple
eudesmanoids, santonin 2, ilicic acid 3, and
a-cyperone 4 are
among the wellknown examples, Fig. 1.
agarofurans like a-agarofuran 5 have been known for long, highly
oxygenated agarofurans continue to appear in the contemporary
* Corresponding author. Tel.: þ91 40 23134848; fax: þ91 40 23010785; e-mail
addresses: gmsc@uohyd.ernet.in, gmehta43@gmail.com (G. Mehta).
literature with regular frequency.3 Isocelorbicol 6, alatol 7, and
http://dx.doi.org/10.1016/j.tet.2015.01.039
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

R. Senthil Kumaran, G. Mehta / Tetrahedron 71 (2015) 1718e1731
1719
euonyminol 8 are representative examples of dihydroagarofurans
(with -C4 methyl group) in terms of degree of oxy-
functionalization and patterns of stereochemical diversity, Fig. 2.
quaternization of the endocylic vinylic methyl center in (ꢀ)-car-
vone 9 to eventuate as the critical C10 angular methyl group, with
concomitant introduction of an alkene side arm and amplification
of functionality. The other essential requirement was the in-
stallation of the second alkene arm on the carbonyl group to setup
an RCM protocol for the construction of the decalin segment with
requisite C5 bridgehead hydroxyl functionality. The later was to
serve as a handle for the construction of the bridged tetrahydro-
furan moiety. A path towards the actualization of this strategy is
delineated in the retrosynthetic theme presented in Scheme 1. This
envisaged setting-up the RCM in a di-allylic precursor like 10 to
deliver the eudesmane derivative 11 and further acid mediated
intramolecular oxycyclization to generate the tetrahydrofuran ring
bearing tricyclic system 12.
b
Fig. 2. Representative oxygenated dihydroagarofurans.
Scheme 1. A general retrosynthetic theme for the constructing of eudesmanes and
dihydroagarofurans.
Dihydroagarofuran subclass is particularly notable for its wide
occurrence in the plant extracts of Celestraceae family,3a,5 which has
evoked much attention in recent years as they display impressive
bioactivity profile.3,5 In addition to activity against various types of
cancer and rheumatoid arthritis,6 agarofurans have drawn attention
as promising multi-drug resistance reversal agents against Myco-
bacterium tuberculosis bacteria,6a Leishmania tropica protozoan
parasite6b as well as against specific cancer cells6c due to their ability
to inhibit the expression of P-glycoprotein (Pgp)-like transporters.
For reasons of functional diversity and density, promising bio-
activity leads and potential as attractive platforms for devising and
testing new synthetic strategies, eudesmanes and agarofurans have
been objects of numerous synthetic forays by organic chemistry
community for nearly half a century.7,8 Since, agarofuran frame-
work has come to be regarded as a ‘privileged’ structure, its siblings
In order to execute the theme outlined in Scheme 1, (ꢀ)-carvone
9 was subjected to stereo- and regioselective epoxidation in the
presence of alkaline H2O2 to afford
b
-epoxide (þ)-13 as a single
diastereomer.13 Reductive allylation of carvone epoxide (þ)-1314 in
Li/liq. ammonia milieu resulted in the formation of four di-
astereomers (þ)-14, (þ)-15, (þ)-16, and (þ)-17 in a ratio of
w10.5:9.5:1:1 (Scheme 2). All the four allylated products
(þ)-14e(þ)-17 were amenable to chromatographic separation and
their stereostructures were indicated through a careful analyses of
their 1H and 13C NMR spectral data and further secured through
single crystal structure determination of advanced intermediates
emanating from them (vide infra). Formation of diastereomers
(þ)-15 and (þ)-17, with
a-hydroxyl groups, indicated that they
like 4-desmethyl (nor-dihydroagarofuran), 4
a-methyl (iso-dihy-
were not formed from epoxide (þ)-13 through a straightforward
reductive allylation. Similarly, formation of (þ)-16 and (þ)-17 with
apparent retention of quaternary methyl group stereochemistry
was indicative of a much involved process. Indeed, the formation of
four allylated products 14e17 could be reconciled in terms of initial
formation of a dianion 18, which is quenched by allyl bromide to
generate an intermediate 19, which undergoes eventful retro-aldol
in 19 and re-aldolisation 20 under the given reaction conditions,
Scheme 2.
droagarofuran), and 4 -methyl (dihydroagarofuran) and their var-
b
iants, have also been receiving attention.
In general, strategies based on the variants of Robinson annu-
lation, inter- and intramolecular DielseAlder reaction, reductive
dearomatization,
biomimetic
cyclization,
chiron
based
approaches and ring closure metathesis (RCM) among others have
been devised, in both racemic as well as chiral variants, for the
construction of the eudesmane framework with attendant func-
tional embellishments.6 Among these approaches, ones that utilize
monoterpene carvone9 are potentially more versatile as this chiron
is commercially accessible in both its enantiomeric forms and in
topological terms its C-10 monoterpene framework fully maps into
the C-15 eudesmane carbon skeleton. As part of our long standing
interest10 in utilizing abundant terpenes as chirons in total syn-
thesis through restructuring and grafting, we contemplated a new
(ꢀ)-carvone 9 based approach to eudesmanes and dihydroagar-
ofurans in which RCM constitutes a key step. This strategy appeared
to be flexible in terms of stereochemical and functional group di-
versity and had potential to be of general applicability. In this11 and
the accompanying paper,12 we explore and detail our diversity
driven approach to eudesmane and agarofuran frameworks based
on (ꢀ)-carvone as chiron.
Among the four diastereomers (þ)-14e(þ)-17 formed (Scheme
2), the two major diastereomers (þ)-14 and (þ)-15 were epimeric
at the hydroxyl bearing carbon as they furnished the same ketone
21 on oxidation. They were also accessible in good amounts and
therefore serviceable for further elaboration towards the desired
eudesmanes and dihydroagarofurans. In this regard, it is important
to note that the securely installed hydroxyl groups in (þ)-14 and
(þ)-15 were destined to eventuate at C9 position in eudesmane and
agarofuran framework, an essential functionality for the synthesis
of the more embellished members of this class of natural products.
Thus, both (þ)-14 and (þ)-15 were processed independently but
first our travails with
a
-hydroxylketone (þ)-15 and we will revert
to
b
a
-hydroxylketone (þ)-14 later in the sequel.
-Hydroxylketone (þ)-15 on Grignard-type addition of allyl-
magnesiumchloride led to a mixture of two diastereomeric bis-
2. Results and discussions
allylated diols in a ratio of 5.5:1 in which (ꢀ)-22 was the major
product besides its unwanted
a
-face addition epimer (þ)-23,
The conceptual foundation of our approach to eudesmanes and
agarofuran framework had two key elements. The first required
Scheme 3. The diastereoselectivity leading to preferred formation
of (ꢀ)-22 could be attributed to addition from the less hindered
b-

1720
R. Senthil Kumaran, G. Mehta / Tetrahedron 71 (2015) 1718e1731
Scheme 2. Reagents and conditions: (a) 30% H2O2, 6 N NaOH, MeOH, e10 ꢁC, 92%; (b) Li, liq. NH3, ether, CH2]CHCH2Br, e78 ꢁC, (þ)-14:(þ)-15:(þ)-16:(þ)-17 in the ratio of
(10.5:9.5:1:1), 66% and possible mechanistic pathway for the formation of hydroxylketones (þ)-14e(þ)17; (c) PCC, DCM, rt, 85%.
face, opposite to the pre-existing bulky isopropenyl and allyl
groups, which sterically shield the -face. This steric control offered
an opportunity to further improve diastereoselectivity during the
Grignard addition by making the -face in 15 more sterically en-
cumbered. Thus, it was pleasing to observe that Grignard addition
of allylmagnesiumchloride to the benzoate protected derivative
(þ)-24 of (þ)-15 was highly stereoselective and furnished only the
diastereomer (ꢀ)-22 with concomitant deprotection of the ben-
zoate protection, Scheme 3. RCM reaction was now performed on
the bisallyl compound 22 by exposure to Grubbs’ first generation
(G1) catalyst to smoothly furnish noreudesmane derivative (ꢀ)-25,
Scheme 3.
anticipated, addition of the Grignard reagent to the carbonyl group
in this case was also stereoselective (from -face) to install the C5
a
b
quaternary center but the two diastereomers (þ)-28 and (þ)-29
were epimeric at the carbon (*) bearing the secondary methyl
group. The two diols (þ)-28 and (þ)-29 were carried forward in-
a
dependently with the former leading to iso-dihydroagarofuran (4a-
methyl) and the latter to dihydroagarofuran (4b-methyl) series.
Initially, the major diol (þ)-28 was subjected to RCM reaction using
Grubbs’ (G1) catalyst to smoothly and efficiently deliver the
eudesmane (þ)-30. Stereostructure of 30 was secured through
a single crystal X-ray structure on its PNB-derivative 31 and an
ORTEP is displayed in Scheme 4.
Scheme 3. Reagents and conditions: (a) BzCl, Et3N, DMAP, DCM, rt, 88%; (b) CH2]
CHCH2MgCl, THF, e78 ꢁC, (ꢀ)-22:(þ)-23¼5.5:1, 67%; (c) 10 mol % Grubbs’ cat., C6H6,
80 ꢁC, 78%; (d) BzCl, Et3N, DMAP, DCM, rt, 95%; (e)TfOH, THF, 0 ꢁC, 85%.
Scheme 4. Reagents and conditions: (a) CH2]CHCH(CH3)MgCl, THF, e78 ꢁC,(þ)-
29:(þ)-28 in the ratio of (1: 2), 72%; (b) 7 mol % Grubbs’ cat, C6H6, 80 ꢁC, 75%; (c)
PNBCl, Et3N, DMAP, DCM, rt, 88%.
The secondary hydroxyl group in (ꢀ)-25 was selectively pro-
tected as benzoate (þ)-26 and the proximate, axially disposed, C5
hydroxyl and C7 isopropenyl group were coaxed into acid mediated
intramolecular etherification by exposure to triflic acid. Indeed,
tricyclic nor-dihydroagarofuran (ꢀ)-27 was released smoothly and
in good yield, Scheme 3.
In the back drop of this model study towards noreudesmane
(þ)-26 and tricyclic nor-dihydroagarofuran (ꢀ)-27, the next obvi-
ous step was to adapt it for the construction of the eudesmane and
dihydroagarofuran framework by ensuring the installation of the
requisite C4 methyl group in ring A. Towards this end, hydroxyl
protected benzoate (þ)-24 was reacted with the Grignard reagent
derived from 3-chloro-1-butene to obtain a 2:1 mixture of readily
separable diastereomers (þ)-28 and (þ)-29, again with the con-
current deprotection of the benzoate group, Scheme 4. As
The stage was now set to induce intramolecular carbocation
mediated oxycyclization among axially poised C7 isopropenyl and
C5 hydroxyl groups in eudesmane (þ)-30 to the dihydroagarofuran
32. However, exposure of 30 to triflic acid only led to the double
bond isomerized product 33 and the contemplated oxycyclization
to 32 was not observed, Scheme 5. It appeared that in (þ)-30, the
axially disposed tertiary hydroxyl group at C5 and the secondary
hydroxyl group at C9 are locked in a strong intramolecular hydro-
gen bonding and therefore the intramolecular nucleophile at C5 is
not available for cyclization. One way to validate this assumption
was to derivatize the bystander C9 hydroxyl group in 30 involved in
hydrogen bonding. Indeed, the benzoate (þ)-34 prepared from 30
on brief exposure to triflic acid delivered iso-dihydroagarofuran
derivative (þ)-35 (4
a-methyl series) quite uneventfully, Scheme 5.

R. Senthil Kumaran, G. Mehta / Tetrahedron 71 (2015) 1718e1731
1721
can be rationalized in terms of chelation controlled addition with b-
hydroxyl participation as shown in 39. Ring closure metathesis in
(ꢀ)-40 employing Grubbs’ (G1) catalyst led to the noreudesmane
derivative C5,C9 cis-diol (þ)-41 and its stereostructure was fully
secured through single crystal X-ray structure determination of
(þ)-41 and the ORTEP is displayed in Scheme 7. To further evolve
(þ)-41, particularly in the context of dihydroagarofuran natural
product synthesis, required inversion of C9 hydroxyl group ste-
reochemistry as in good many natural products it is usually in a-
orientation. This was accomplished by oxidation of the secondary
hydroxyl group in (þ)-41 to hydroxylketone (ꢀ)-42 and modestly
diastereoselective sodium borohydride reduction to (þ)-43,
Scheme 8. Protection of C9 hydroxyl group as benzoate (þ)-44 and
dehydration of the tertiary hydroxyl group led to triene (þ)-45.
Regioselective oxymercuration in (þ)-45 led to the installation of
hydroxyl-isopropyl moiety in (þ)-46, Scheme 8. Epoxidation of
(þ)-46 with meta-chloroperbenzoic acid was moderately regiose-
lective and epoxide (þ)-48 was released along with the C2,C3 ep-
oxide (þ)-47 (4:1). As planned, exposure of (þ)-48 to BF3-etherate
led to intramolecular hydroxyl mediated opening to deliver nor-
dihydroagarofuran (ꢀ)-49 and its stereostructure was secured
through single crystal X-ray structure determination. An ORTEP
diagram is displayed in Scheme 8.
Scheme 5. Reagents and conditions: (a) BzCl, Et3N, DMAP, DCM, rt, 85%; (b) TfOH, THF,
0
ꢁC, 83%; (c) TfOH, THF, 0 ꢁC, 60%.
It was time to further test the efficacy and generality of our
approach by targeting a natural product like isocelorbicol 6 em-
bodying a dihydroagarofuran moiety, Fig. 2.15 This natural product
has a 4
b
-methyl group (cf. 32 with a 4
a-methyl group) and there-
fore our attention turned to the minor 4
b-methyl epimer (þ)-29
obtained during the addition of 3-chloro-1-butene derived
Grignard reagent to (þ)-24 (Scheme 4). Ring closure metathesis
reaction in 29 with Grubbs’ (G1) catalyst readily generated the
eudesmane skeleton (ꢀ)-36. The C9 hydroxyl group in (ꢀ)-36 was
now protected as benzoate (ꢀ)-37 and its further exposure to triflic
acid led to the carbocation mediated cyclization to dihydroagar-
ofuran framework (ꢀ)-38 (Scheme 6). The spectral data (IR & NMR)
of (ꢀ)-38 were found to be identical with the Huffman’s advance
intermediate16 in the synthesis of racemic isocelorbicol 6. Thus, our
short access to (ꢀ)-38 constitutes a formal enantioselective syn-
thesis of the agarofuran based polyol isocelorbicol 6, Scheme 6.
Scheme 7. Reagents and conditions: (a) CH2]CHCH2MgCl, THF, _78 ꢁC, 90%; (b)
5 mol % Grubbs’ cat., C6H6, 80 ꢁC, 95%.
Encouraged by the success in constructing the nor-
dihydroagarofuran framework with C6 oxy-functionality, we ex-
tended the foregoing studies to construct the complete dihy-
droagarofuran framework. Addition of Grignard reagent prepared
from 3-chloro-1-butene to (þ)-14 in the presence of Ce(III) de-
livered diallylated diastereomers (ꢀ)-50 and (ꢀ)-51 in a ratio of
1:1.2, Scheme 9. The two hydroxy diols (ꢀ)-50 and (ꢀ)-51 were
epimeric at the secondary methyl bearing center (*) but the addi-
Scheme 6. Reagents and conditions: (a) 7 mol % Grubbs’ cat, C6H6, 85 ꢁC, 70%; (b) BzCl,
Et3N, DMAP, DCM, rt, 83%; (c) TfOH, THF, 0 ꢁC, 90%.
tion to the carbonyl group was
case also, the highly face selective Grignard addition occurred in an
intuitively less predictable manner, from the -face and the ste-
a-face selective. Interestingly, in this
It was now opportune to return to the
b
-hydroxylketone (þ)-14,
the second major product obtained during the reductive allylation
of the carvone epoxide (þ)-13, see Scheme 2, and advance it further
to amplify the scope of our approach and create stereochemical
diversity and additional functionalities on the eudesmane/dihy-
droagarofuran frameworks. An added intent was to undertake re-
course to tactics that would enable introduction of C6 hydroxy
functionality on a prefabricated eudesmane platform, an expedi-
tious requirement in the context of agarofuran synthesis (Figs. 1
and 2).
a
reochemical outcome can possibly be explained in terms of chela-
tion controlled, hydroxy directed addition, as indicated in 52, from
the more hindered face, Scheme 9. Both, (ꢀ)-50 and (ꢀ)-51 were
now poised for RCM reaction using G1 catalyst to furnish the cor-
responding eudesmane derivatives. First, (ꢀ)-51 was exposed to G1
catalyst to smoothly furnish
4a-methyleudesmane derivative
(þ)-53. Stereostructure of (þ)-53 was secured through X-ray
structure determination of PNB-derivative 54, Scheme 9. Since,
Accordingly, (þ)-14 was subjected to addition of Grignard re-
agent allylmagnesiumchloride to deliver a cis-diol (ꢀ)-40 as a sin-
gle diastereomer, Scheme 7. Formation of (ꢀ)-40 was contra-
intuitive in the sense that the addition took place from the more
(þ)-53 belonged to 4
lead to the iso-dihydroagarofuran (4
pursued further. Attention was now shifted to the diastereomer
(ꢀ)-50 with secondary -methyl group. On exposure to Grubbs’
(G1) catalyst, (ꢀ)-50 smoothly led to the 4 -methyleudesmane
a
-methyleudesmane series and was likely to
a
-methyl) series, it was not
b
hindered
a-face (cf. addition to (þ)-14, Scheme 7) but the outcome
b

1722
R. Senthil Kumaran, G. Mehta / Tetrahedron 71 (2015) 1718e1731
Scheme 8. Reagents and conditions: (a) PCC, DCM, rt, 87%; (b) NaBH4, MeOH, (þ)-41:(þ)-43 in the ratio of (1.5:1), 0 ꢁC, 95%; (c) BzCl, Et3N, DMAP, DCM, 90%; (d) SOCl2, Py, ꢀ35 ꢁC,
81%; (e) Hg(OAc)2, THF/H2O, cat. AcOH, rt, NaBH4 in NaOH, 76%; (f) mCPBA, NaHCO3, DCM, (þ)47:(þ)-48 in a ratio of (1:4), 0 ꢁC, 83%; (g) BF3$Et2O, DCM, 0 ꢁC, 92%.
derivative (ꢀ)-55, Scheme 10. To advance (ꢀ)-55 further towards
a natural product target, C9 -hydroxyl group needed to be inver-
stereoselectivity during the reduction of 56 to access the required
-hydroxyl epimer 57 was low, it was still serviceable as the major
b
9a
ted. Initial attempts using the otherwise reliable Mitsunobu pro-
tocol in its many variants were unsuccessful. Thus, recourse was
taken to an indirect route, which required regioselective oxidation
of (ꢀ)-55 to the C9 ketone (ꢀ)-56 and further sodium borohydride
isomer (ꢀ)-55 could be recycled via 56 to build-up enough mate-
rial. Chemoselective benzoylation of (ꢀ)-57 led to (þ)-58 and fur-
ther regiospecific dehydration of the C5 tertiary hydroxyl group
delivered the bicyclic triene (þ)-59, Scheme 10. This triene was an
reduction to furnish a (4:1) mixture of (ꢀ)-55 and the desired C9
a
-
appropriate
substrate
for
extensive,
sequential,
oxy-
hydroxyl compound (ꢀ)-57, Scheme 10. Although the
functionalization of the eudesmane framework with concurrent
installation of the bridged tetrahydrofuran moiety to generate the
dihydroagarofuran system. This objective was accomplished
through sequential oxymercuration, osmylation, and epoxidation
protocol. In the event, oxymercuration in (þ)-59 was regiospecific
and only the isopropenyl moiety was selectively hydrated to fur-
nish (ꢀ)-60. Epoxidation in (ꢀ)-60 was non-regioselective and
furnished a readily separable mixture (4:5) of the required 5
epoxide 61 and an unwanted 2 ,3 -epoxide 62, Scheme 10. The
bicyclic 5 ,6 -epoxide 61 on exposure to BF3-etherate furnished
b,6b-
a
a
b
b
the desired dihydroagarofuran (ꢀ)-63, Scheme 10. While our ob-
jective had made considerable headway, we desired to improve the
regioselectivity during the epoxidation of (see (ꢀ)-60 to 61) and
also amplify the oxygen network on the eudesmane framework.
Towards this purpose, (ꢀ)-60 was first subjected to catalytic
OsO4-mediated dihydroxylation, which was both regio- and ster-
eoselective to furnish 2,3-dihydroxylated eudesmane (þ)-64 with
preferred addition from the
methyl harboring top face, Scheme 11. In order to engender in-
creased steric bias on the -face of 64, the cis-diol moiety was
a-face, opposite to the b-C4 and b-C10
Scheme 9. Reagents and conditions: (a) CH2]CHCH(CH3)MgCl, anhyd CeCl3, THF,
e78 ꢁC, (ꢀ)-50:(ꢀ)-51 in the ratio of (1:1.2), 95%; (b) 7 mol % Grubbs’ cat., C6H6, 80 ꢁC,
89%; (c) PNBCl, Et3N, DMAP, DCM, rt, 85%.
a
Scheme 10. Reagents and conditions: (a) 5 mol % Grubbs’ cat., C6H6, 80 ꢁC, 95%; (b) PCC, DCM, rt, 78%; (c) NaBH4, MeOH, (ꢀ)-55:(ꢀ)-57 in the ratio of (4:1), 0 ꢁC, 90%; (d) BzCl, Et3N,
DMAP, DCM, 87%; (e) SOCl2, Py, ꢀ35 ꢁC, 80%; (f) Hg(OAc)2, THF/H2O, NaBH4 in NaOH, 70%; (g) mCPBA, DCM, NaHCO3, 61:62 in the ratio of (4:5), 0 ꢁC, 83%; h) BF3.Et2O, DCM, 0 ꢁC,
92%.

R. Senthil Kumaran, G. Mehta / Tetrahedron 71 (2015) 1718e1731
1723
protected as an acetonide (þ)-65. In 65, the
a
-face of the molecule
chemical shifts are expressed in parts per million (
d
) downfield
was effectively shielded by the presence of bulky C2,C3-acetonide
moiety, C7-hydroxyisopropyl group, and the C9 benzoate func-
tionality and this ensured stereoselectivity during the last oxidation
maneuver on it involving epoxidation of the C5,C6 double bond.
Indeed, epoxidation of acetonide 65 with meta-chloroperbenzoic
from Me4Si. The standard abbreviations s, d, t, q, and m refer to
singlet, doublet, triplet, quartet, and multiplet, respectively. Mass
Spectra were recorded either on Shimadzu, GCMS-QP 5050A or on
Q-TOF Micromass mass spectrometers.
All the crystals were obtained using slow evaporation technique
from either single or a mixture of solvents. The X-ray data were
acid turned out to be
b-face selective and exclusively delivered
(ꢀ)-66. Exposure of (ꢀ)-66 to TMSOTf resulted in intramolecular
hydroxyl mediated epoxide opening and the generation of the
bridged tetrahydrofuran moiety with concurrent acetonide
deprotection to furnish (ꢀ)-67, Scheme 11. Stereostructure of
(ꢀ)-67 was fully secured through single crystal X-ray structure
determination and an ORTEP diagram is displayed in Scheme 11.
collected on a Bruker AXS SMART APEX CCD diffractometer with
ꢀ
graphite monochromated Mo K
a
radiation (
l
¼0.7107 A). The X-ray
generator was operated at 50 kV and 35 mA power supply. The data
were collected with a
scan width of 0.3ꢁ. A total of 606 frames per
u
set were collected using SMART in four different settings of 4 (0ꢁ, 90ꢁ,
180ꢁ, 270ꢁ) for triclinic crystal systems and three settings 4 (0ꢁ, 90ꢁ,
180ꢁ) for crystal systems of higher symmetry. The data were reduced
by SAINTPLUS; an empirical absorption correction was applied using
SADABS and space group was determined by XPREP. The structure
was solved by direct methods (SIR92). Refinement was done by full-
matrix least squares procedures on F2 using SHELXL-97. The non-
hydrogen atoms were refined anisotropically, whereas hydrogen
atoms were refined isotropically. Molecular and packing diagrams
were generated using ORTEP32 in the WINGX program. All the
crystallographic data (excluding structure factors) have been de-
posited with the Cambridge Crystallographic Data Center. This data
can be obtained by free of charge via www.ccdc.cam.ac.uk/conts/
retrieving.html (or deposit@ccdc.cam.ac.uk).
4.1.1. Preparation of carvone epoxide (þ)-13. To a stirred solution of
(ꢀ)-carvone 9 (23.5 mL, 0.15 mol) in MeOH (150 mL) was added 30%
H2O2 (33 mL, 0.3 mol) at ꢀ10 ꢁC. Freshly prepared 6 N NaOH so-
lution (15 mL) was added drop wise to the reaction mixture over
a period of 1 h. The reaction mixture was stirred at the same
temperature for 3 h. The reaction mixture was diluted with water
(200 mL) and extracted with diethyl ether (ether) (3ꢂ100 mL). The
combined extract was washed with water (30 mL), brine (30 mL)
and dried over anhydrous Na2SO4. The crude material was filtered
through a silica gel pad to furnish 22.9 g of carvone epoxide (þ)-13
Scheme 11. Reagents and conditions: (a) OsO4, NMO, CH3COCH3/H2O (4:1), rt, 95%; (b)
Amberlyst-15, acetone, rt, 81%; (c) mCPBA, NaHCO3, DCM, 0 ꢁC, 90%; (d) TMSOTf, DCM,
0
ꢁC, 55%.
3. Conclusion
In summary, a short, general, and flexible synthesis of eudes-
mane skeleton from R-(ꢀ)-carvone, employing RCM as a key step
has been achieved. This general approach has been refined and
amplified towards the synthesis of diverse polyhydroxylated
dihydroagarofurans and analogous nor-dihydroagarofurans and
iso-dihydroagarofurans by dovetailing RCM with either carbocation
mediated intramolecular oxycyclization or Lewis acid catalyzed
epoxide ring opening steps to generate the tetrahydrofuran moiety.
As an example of the utility of this strategy, a formal synthesis of
natural product isocelorbicol has been accomplished.
(92%) as a colorless liquid. [
1709 cmꢀ1
a
]
24 þ47.7 (c 1.3, CHCl3); IR (neat): nmax
D
.
4.1.2. Synthesis of (þ)-14, (þ)-15, (þ)-16, and (þ)-17. To a distilled
and degassed (with argon) solution of liq. NH3 (1.5 L) was added
lithium metal (1.75 g, 0.25 mol). After the addition of lithium, the
color of the solution turned dark blue and then the reaction mixture
was allowed to stir for 15 min. The epoxide (þ)-13 (20 g, 0.12 mol)
dissolved in dry ether (150 mL) was added drop wise to the reaction
mixture over a period of 45 min at ꢀ78 ꢁC. Once the addition was
over, the reaction was allowed to stir at ꢀ33 ꢁC for another 1.5 h. The
reaction mixture was again brought back to ꢀ78 ꢁC and allyl bro-
mide (10.4 mL, 0.12 mol) in dry ether (50 mL) was added to the
reaction mixture over a period of 30 min and stirred at the same
temperature for 1 h. The reaction was quenched with saturated
NH4Cl followed by the addition of the solid NH4Cl and the reaction
was left for the complete evaporation of ammonia. The residue was
diluted with water and extracted with ether (3ꢂ250 mL). The
combined ether extract was washed with water (50 mL) and 10% HCl
solution (30 mL) and brine (50 mL), respectively. The crude material
was purified through silica gel column chromatography to afford
a mixture of diastereomers in a ratio of (1:1:9.5:10.5). The column
was first eluted with 60% DCM/hexane to deliver 750 mg of com-
pound (þ)-16 and further successive elution with 80% DCM/hexane,
2% EtOAc/DCM, and 10% EtOAc/DCM delivered 750 mg of (þ)-17,
7.1 g of (þ)-15, and 7.9 g of (þ)-14, respectively (66%).
4. Experimental section
4.1. General information
All common reagents and commercial grade solvents were ob-
tained from local suppliers and distilled by standard methods and
used without further purification. Thin layer chromatography was
performed on microscopic slides coated with silica gel (GF-254
mesh, Merck). Visualization of spots was accomplished by exposure
to iodine vapor and/or UV radiation and/or spraying with ethanolic
vaniline solution followed by charring. Column chromatography
was performed over silica gel (100e200 mesh) and various com-
binations of ethyl acetate and hexane were used as eluents. Melting
points reported are uncorrected. Infrared spectra were recorded on
JASCO FT-IR 410 spectrometer. The samples were recorded either as
thin films or between NaCl plates. Unless otherwise mentioned,
NMR spectra were recorded on JEOL JNM-LA 300 or Bruker 400
instruments in CDCl3 solutions. Chemical shifts are reported with
respect to tetramethylsilane (Me4Si) as the internal standard (for 1H
NMR) and the central line (77.0 ppm) of CDCl3 (for 13C NMR). The
4.1.3. (2R,3R,5R)-2-Allyl-3-hydroxy-5-isopropenyl-2-methyl-
cyclohexan-1-one (þ)-16. [
a
]
25 þ41.6 (c 3.2, CHCl3); IR (neat): nmax
D
3484, 1701 cmꢀ1
;
1H NMR (300 MHz, CDCl3):
d
5.95e5.81 (m, 1H),

1724
R. Senthil Kumaran, G. Mehta / Tetrahedron 71 (2015) 1718e1731
5.15 (d, J¼13.5 Hz, 1H), 5.11 (d, J¼8.1 Hz, 1H), 4.78 (s, 1H), 4.74 (s,
1H), 3.99 (s, 1H), 2.91e2.80 (m, 1H), 2.63e2.45 (m, 2H), 2.39e2.29
(m, 2H), 2.08e2.01 (m, 1H), 1.98e1.93 (m, 1H), 1.75 (s, 3H), 1.15 (s,
5.94e5.80 (m, 1H), 5.18e5.01 (m, 4H), 4.74 (s, 2H), 3.75e3.64 (m,
1H), 2.50e2.31 (m, 4H), 2.07e1.94 (m, 1H), 1.85e1.76 (m, 1H), 1.74
(s, 3H), 1.66e1.51 (m, 3H), 1.16 (s, 3H); 13C NMR (75 MHz, CDCl3):
3H); 13C NMR (75 MHz, CDCl3):
d
214.0, 147.2, 134.6, 118.3, 110.0,
d 148.0, 138.6, 133.8, 118.4, 116.6, 109.0, 77.1, 75.9, 46.3, 38.8, 38.1,
74.9, 51.9, 42.4, 39.1, 37.4, 33.0, 21.4, 20.6; HRMS (ES): m/z calcd for
C
36.5, 34.7, 34.6, 20.8, 17.2; HRMS (ES): m/z calcd for C16H26O2Na
13H20O2Na (MþþNa): 231.1361; found: 231.1367.
(MþþNa): 273.1830; found: 273.1848.
4.1.4. (2R,3S,5R)-2-Allyl-3-hydroxy-5-isopropenyl-2-methyl-cyclo-
4.1.10. (1S,2S,3S,5R)-1,2-Diallyl-5-isopropenyl-2-methylcyclohexane-
24
hexan-1-one (þ)-17. [
a
]
D
25 þ42.9 (c 1.6, CHCl3); IR (neat): nmax 3451,
1,3-diol (þ)-23. [
a]
þ18.2 (c 1.4, CHCl3); IR (neat): nmax 3457,
D
1704 cmꢀ1
;
1H NMR (300 MHz, CDCl3):
d
5.96e5.82 (m, 1H),
1637 cmꢀ1 1H NMR (300 MHz, CDCl3):
; d 6.15e6.01 (m, 1H),
5.17e5.06 (m, 2H), 4.80 (s, 1H), 4.76 (s, 1H), 3.87 (dd, J¼11.4, 4.5 Hz,
1H), 2.59e2.52 (m, 1H), 2.49 (d, J¼14.1 Hz, 1H), 2.33 (dd, J¼3.6,
2.1 Hz, 1H), 2.30e2.23 (m, 1H), 2.18 (td, J¼13.2, 3.6 Hz, 1H),
2.06e1.99 (m, 1H), 1.85e1.83 (m, 1H), 1.75 (s, 3H), 1.16 (s, 3H); 13C
5.93e5.79 (m, 1H), 5.24e5.02 (m, 4H), 4.73 (s, 2H), 3.97e3.89 (m,
1H), 2.53e2.33 (m, 3H), 2.24 (dd, J¼13.5, 6.6 Hz, 1H), 2.07 (dd,
J¼14.4, 6.3 Hz, 1H), 1.89e1.85 (m, 1H), 1.75 (s, 3H), 1.65e1.39 (m,
3H), 1.19 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 148.9, 137.6, 133.5,
NMR (75 MHz, CDCl3):
d
212.6, 146.5, 135.7, 117.8, 110.2, 72.7, 54.2,
120.3, 116.6, 108.9, 76.1, 75.1, 45.7, 41.1, 38.1, 36.9, 36.0, 35.5, 20.9,
16.0; HRMS (ES): m/z calcd for C16H26O2Na (MþþNa): 273.1830;
found: 273.1852.
42.4, 39.1, 39.0, 34.5, 20.4, 17.7; HRMS (ES): m/z calcd for
C
13H20O2Na (MþþNa): 231.1361; found: 231.1369.
4.1. 5. (2S, 3S, 5R)-2-Allyl-3-hydroxy-5-isopropenyl-2-
4.1.11. (1S,2S,5R)-2-Allyl-5-isopropenyl-2-methyl-3-oxocyclohexyl
benzoate (þ)-24. To a dry DCM (10 mL) solution of the alcohol
(þ)-15 (550 mg, 2.64 mmol) were added Et3N (1.1 mL, 7.92 mmol),
DMAP (32 mg, 0.26 mmol), and BzCl (0.46 mL, 3.96 mmol) at 0 ꢁC.
The reaction was stirred at room temperature for 10 h. The reaction
was quenched by careful addition of ice-cold water and diluted
with DCM (60 mL). The organic extract successively washed with
water (20 mL), sodium bicarbonate solution (15 mL), and brine. The
crude material was purified through a silica gel column (2% EtOAc/
hexane) to furnish 726 mg of benzoate (þ)-24 (88%) as a colorless
23
methylcyclohexan-1-one (þ)-15. Mp: 51e52.5 ꢁC; [
a]
þ121.3 (c
D
0.9, CHCl3); IR (thin film): nmax 3453,1700 cmꢀ1; 1H NMR (300 MHz,
CDCl3):
1H), 3.64 (t, J¼5.4 Hz, 1H), 2.70e1.80 (m, 7H), 1.75 (s, 3H), 1.15 (s,
3H); 13C NMR (75 MHz, CDCl3):
212.3, 146.4, 132.8, 118.2, 110.3,
d 5.74e5.50 (m, 1H), 5.08e5.01 (m, 2H), 4.80 (s, 1H), 4.76 (s,
d
76.7, 54.8, 42.9, 39.4, 36.0, 34.5, 20.4, 18.2; HRMS (ES): m/z calcd for
C
13H20O2Na (MþþNa): 231.1361; found: 231.1370.
4.1. 6. (2S, 3R, 5R)-2-Allyl-3-hydroxy-5-isopropenyl-2-
23
methylcyclohexan-1-one (þ)-14. Mp: 57.5e58.5 ꢁC; [
a]
þ65.2 (c
liquid; [
a
]
24 þ92.3 (c 3.5, CHCl3); IR (neat): nmax 1716 cmꢀ1; 1H NMR
D
D
1.6, CHCl3); IR (thin film): nmax 3473, 1702 cmꢀ1; 1H NMR (300 MHz,
(300 MHz, CDCl3):
d
8.04 (d, J¼7.4 Hz, 2H), 7.60 (t, J¼7.4 Hz,1H), 7.45
CDCl3):
d
5.67e5.53 (m, 1H), 5.08 (s, 1H), 5.04 (s, 1H), 4.79 (s, 1H),
(t, J¼7.4 Hz, 2H), 5.69e5.55 (m, 1H), 5.15e5.06 (m, 3H), 4.82 (s, 1H),
4.79 (s, 1H), 2.75 (dd, J¼14.1, 7.5 Hz, 1H), 2.57e2.50 (m, 1H),
2.47e2.44 (m, 1H), 2.42e2.23 (m, 2H), 2.07 (t, J¼12.0 Hz, 1H), 1.76
(s, 3H), 1.74e1.71 (m, 1H), 1.15 (s, 3H); 13C NMR (75 MHz, CDCl3):
4.73 (s, 1H), 3.98 (s, 1H), 2.87e2.79 (m, 1H), 2.52e2.37 (m, 3H),
2.28e2.21 (m, 1H), 2.14e1.92 (m, 2H), 1.75 (s, 3H), 1.11 (s, 3H); 13C
NMR (75 MHz, CDCl3):
d 213.6, 147.1, 132.4, 118.5, 110.1, 75.5, 53.3,
42.7, 41.2, 39.0, 32.6, 20.8, 17.2; HRMS (ES): m/z calcd for
C
d 210.1, 165.5, 145.9, 133.2, 132.2, 129.9, 129.5 (2C), 128.5 (2C), 118.6,
13H20O2Na (MþþNa): 231.1361; found: 231.1370.
110.5, 77.8, 55.5, 43.1, 39.0, 37.3, 31.3, 20.5, 18.5; HRMS (ES): m/z
calcd for C20H24O3Na (MþþNa): 335.1623; found: 335.1608.
4.1.7. 2-Allyl-5-isopropenyl-2-methyl-1,3-cyclohexanedione 21. To
a dry DCM (2 mL) solution of compounds (þ)-14 or/and (þ)-15
(10 mg, 0.05 mmol) was added PCC (20 mg, 0.1 mmol) along with
4 .1.12 . ( 1 R , 2 S , 3 S , 5 R ) - 1, 2 - D i a l l y l - 5 - i s o p r o p e n y l - 2 -
methylcyclohexane-1,3-diol (ꢀ)-22. The allyl Grignard reagent was
first prepared by following the same procedure as described earlier.
To an ice-cooled solution of the ketone (þ)-24 (130 mg, 0.42 mmol)
in dry THF (2 mL) was added drop wise the freshly prepared 1 M
solution of Grignard reagent (1 mL, 1 mmol) at ꢀ78 ꢁC and allowed
to stir at the same temperature for 1 h. The reaction was quenched
with saturated NH4Cl solution and diluted with ether (30 mL). The
organic extract was washed with water (4 mL), 10% HCl (4 mL),
brine and dried over anhydrous Na2SO4. The concentrated material
was charged on a silica gel column (15% EtOAc/hexane) to obtain
ꢀ
4 A mol. sieves and stirred for 1 h at room temperature. The re-
action mixture was filtered through a silica gel column to deliver
8 mg of 21 (85%); IR (neat): nmax 1697 cmꢀ1 1H NMR (300 MHz,
;
CDCl3): d 5.62e5.48 (m, 1H), 5.10e5.04 (m, 2H), 4.87 (s, 1H), 4.78 (s,
1H), 2.75e2.63 (m, 4H), 2.55e2.46 (m, 3H), 1.76 (s, 3H), 1.23 (s, 3H);
13C NMR (75 MHz, CDCl3):
43.4, 42.4, 36.8, 20.2, 18.0.
d 209.1, 144.8, 131.6, 119.4, 111.6, 64.5,
4.1.8. Synthesis of (ꢀ)-22 and (þ)-23. Allyl chloride (0.84 mL,
10 mmol) in dry THF (8 mL) was added using an addition funnel to
a stirred suspension of the magnesium turnings (250 mg, 10 mmol)
in dry THF (2 mL) with catalytic amount of iodine at room tem-
perature. After the complete addition of allyl chloride, the reaction
mixture was stirred for another 30 min. The above freshly prepared
1 M solution of Grignard reagent was added drop wise to a solution
of ketone (þ)-15 (20 mg, 0.1 mmol) in dry THF (2 mL) at ꢀ78 ꢁC and
allowed to stir for 1 h. The reaction was quenched with saturated
NH4Cl and diluted with ether (15 mL). The organic extract was
washed with water (2 mL), 10% HCl (2 mL), brine (2 mL) and dried
over anhydrous Na2SO4. The crude material was purified through
a silica gel column to obtain 12 mg of (ꢀ)-22 and 2 mg of (þ)-23 in
a ratio of 5.5:1 (67%).
69 mg of diene (ꢀ)-22 (67%) as a viscous liquid; [
a
]
24 ꢀ23.3 (c 2.7,
D
CHCl3); IR (neat): nmax 3426, 1638 cmꢀ1
.
4.1.13. (1S,3R,4aR,8aS)-3-Isopropenyl-8a-methyl-1,2,3,4,4a,5,8,8a-
octahydro-1,4a-naphthalenediol (ꢀ)-25. A solution of diene (ꢀ)-22
(50 mg, 0.20 mmol) in dry degassed benzene (2 mL) was exposed to
Grubbs’ first generation catalyst (16 mg, 0.02 mmol) and stirred at
room temperature for 4 h. The solvent was removed under reduced
pressure and the reaction mixture was directly charged on a silica
gel column eluting with 6% EtOAc/hexane to afford 35 mg of bicyclic
compound (ꢀ)-25 (78%) as a crystalline solid; mp: 105e105.5 ꢁC;
22
[a
]
ꢀ6.5 (c 1.7, CHCl3); IR (thin film): nmax 3360 cmꢀ1
;
1H NMR
D
(300 MHz, CDCl3):
d 5.77e5.75 (m, 1H), 5.56e5.53 (m, 1H), 5.24 (s,
1H), 4.88 (s, 1H), 3.52 (d, J¼8.7 Hz, 1H), 3.15 (d, J¼9.3 Hz, 1H),
2.91e2.88 (m, 1H), 2.49e2.34 (m, 3H), 2.17e2.00 (m, 3H), 1.89 (s,
3H), 1.85e1.74 (m, 1H), 0.95 (s, 3H); 13C NMR (75 MHz, CDCl3):
4.1.9. (1R,2S,3S,5R)-1,2-Diallyl-5-isopropenyl-2-methylcyclohexane-
24
1,3-diol (ꢀ)-22. [
a
]
D
ꢀ23.3 (c 2.7, CHCl3); IR (neat): nmax 3426,
1638 cmꢀ1
;
1H NMR (300 MHz, CDCl3):
d
6.26e6.12 (m, 1H),
d 149.7, 127.0, 122.4, 110.2, 76.1, 74.1, 39.0, 38.5, 36.4, 33.7, 31.2, 28.9,

R. Senthil Kumaran, G. Mehta / Tetrahedron 71 (2015) 1718e1731
1725
23.5, 22.3; HRMS (ES): m/z calcd for C14H22O2Na (MþþNa):
3.76 (t, J¼5.1 Hz, 1H), 2.62e2.59 (m, 1H), 2.46 (br s, 2H), 2.13e2.09
(m, 1H), 2.00 (s, 1H), 1.88e1.63 (m, 3H), 1.77 (s, 3H), 1.15 (s, 3H), 1.05
245.1517; found: 245.1535.
(d, J¼6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 148.2, 143.4, 138.4,
4.1.14. (1S,3R,4aR,8aS)-4a-Hydroxy-3-isopropenyl-8a-methyl-
1,2,3,4,4a,5,8,8a-octahydro-1-naphthalenyl benzoate (þ)-26. To
a dry DCM (2 mL) solution of (ꢀ)-25 (15 mg, 0.07 mmol) were
added Et3N (0.05 mL, 0.35 mmol), catalytic amount of DMAP (2 mg,
0.01 mmol), and BzCl (0.02 mL, 0.18 mmol) at 0 ꢁC. The reaction was
stirred overnight at room temperature and quenched by careful
addition of water. The organic extract was washed with water
(2 mL), sodium bicarbonate solution (4 mL), and brine, respectively.
The crude material was purified through silica gel column chro-
116.7, 114.1, 109.2, 78.3, 75.8, 47.9, 42.1, 37.7, 36.2 (2C), 33.9, 20.9,
20.7, 18.5; HRMS (ES): m/z calcd for
287.1987; found: 287.2007.
C
17H28O2Na (MþþNa):
4.1.18. (1S,2S,3S,5R)-2-Allyl-5-isopropenyl-2-methyl-1-[(1R)-1-
24
methyl-2-propenyl] cyclohexane-1,3-diol (þ)-29. [
CHCl3); IR (neat): nmax 3432 cmꢀ1 1H NMR (300 MHz, CDCl3):
6.22e6.08 (m, 1H), 5.92e5.79 (m, 1H), 5.19e4.93 (m, 4H), 4.73 (s,
a
]
þ26.0 (c 1.5,
D
;
d
2H), 3.85e3.78 (m, 1H), 2.60e2.48 (m, 3H), 2.26e2.19 (m, 1H),
matography (2% EtOAc/hexane) to furnish 21 mg of benzoate
1.90e1.62 (m, 4H),1.73 (s, 3H),1.21 (s, 3H),1.13 (d, J¼6.6 Hz, 3H); 13
C
23
(þ)-26 (95%) as a colorless liquid; [
a]
þ16.4 (c 3.3, CHCl3); IR
NMR (75 MHz, CDCl3): d 148.6, 142.0, 138.3, 116.8, 113.5, 109.0, 78.2,
D
(neat): nmax 3390, 1716 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d
7.95 (d,
75.3, 47.7, 44.4, 36.9, 35.8 (2C), 33.6, 21.0, 19.0, 17.9; HRMS (ES): m/z
J¼7.5 Hz, 2H), 7.55 (t, J¼7.5 Hz, 1H), 7.42 (t, J¼7.5 Hz, 2H), 5.68e5.62
(m,1H), 5.60e5.55 (m,1H), 5.17 (t, J¼3.3 Hz,1H), 5.10 (s,1H), 4.86 (s,
1H), 3.07 (s, eOH), 2.60e2.49 (m, 3H), 2.28e2.26 (m,1H), 2.20e2.18
(m, 1H), 2.09 (br s, 2H), 1.95e1.92 (m, 1H), 1.75 (s, 3H), 1.49e1.47 (m,
calcd for C17H28O2Na (MþþNa): 287.1987; found: 287.2020.
4.1.19. (1S,3R,4aS,5S,8aS)-3-Isopropenyl-5,8a-dimethyl-
1,2,3,4,4a,5,8,8a-octahydro-1,4a-naphthalenediol (þ)-30. To a solu-
tion of diene (þ)-28 (75 mg, 0.28 mmol) in dry degassed benzene
(4 mL) was added Grubbs’ first generation catalyst (24 mg,
0.03 mmol) and allowed to stir at room temperature for 3e4 h. The
solvent was removed under reduced pressure and the reaction
mixture was directly charged on a silica gel column (10% EtOAc/
1H), 1.14 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 165.8, 148.5, 133.1,
129.8, 129.6 (2C), 128.5 (2C), 125.5, 123.1, 111.2, 77.7, 72.8, 39.5, 37.7,
36.3, 33.7, 31.5, 26.7, 23.2, 22.3; HRMS (ES): m/z calcd for C21H26O3K
(MþþK): 365.1519; found: 365.1605.
4.1.15. (1R,6S,7S,9R)-6,10,10-Trimethyl-11-oxatricyclo[7.2.1.01,6]do-
dec-3-en-7-yl benzoate (ꢀ)-27. To a dry THF (2 mL) solution of the
benzoate (þ)-26 (12 mg, 0.04 mmol) was added triflic acid (TfOH)
(0.01 mL, 0.10 mmol) at 0 ꢁC and stirred for 1 h. The reaction was
quenched by the addition of few drops of water and diluted with
ethyl acetate (10 mL). The extract was washed with water, sodium
bicarbonate solution, brine and dried over anhydrous Na2SO4. The
crude material was charged on a silica gel column (2% EtOAc/hex-
ane) to furnish 10 mg of (ꢀ)-27 (85%) as a white solid; mp:
hexane) to afford 50 mg of (þ)-30 (75%) as a solid; mp: 84e85 ꢁC;
22
[a
]
þ55.2 (c 1.2, CHCl3); IR: nmax 3369 cmꢀ1
;
1H NMR (300 MHz,
5.72 (ddd, J¼10.2, 5.1, 2.7 Hz, 1H), 5.28 (d, J¼10.2 Hz, 1H),
D
CDCl3):
d
5.21 (s, 1H), 4.86 (s, 1H), 3.50e3.47 (m, 1H), 2.88e2.86 (m, 1H),
2.51e2.48 (m, 2H), 2.14e2.10 (m, 2H), 2.01e1.98 (m, 1H), 1.88 (s,
3H), 1.65 (dd, J¼15.0, 7.5 Hz, 1H), 1.50e1.48 (m, 1H), 1.02 (d,
J¼7.2 Hz, 3H), 0.96 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 149.9, 129.7,
125.9, 110.1, 76.6, 75.6, 39.6, 37.9, 36.2, 31.2, 30.2, 28.6, 23.5, 22.3,
12.8; HRMS (ES): m/z calcd for C15H24O2Na (MþþNa): 259.1674;
found: 259.1685.
114e115 ꢁC; [
(300 MHz, CDCl3):
(t, J¼7.5 Hz, 2H), 5.69e5.64 (m, 1H), 5.60e5.53 (m, 1H), 5.15 (d,
J¼7.5 Hz, 1H), 2.89e2.87 (m, 1H), 2.44e2.35 (m, 1H), 2.32e2.29 (m,
1H), 2.08e2.02 (m, 2H), 2.05e1.98 (m, 2H), 1.86 (d, J¼11.7 Hz, 1H),
1.57 (m, 1H), 1.54 (s, 3H), 1.29 (s, 3H), 1.11 (s, 3H); 13C NMR (75 MHz,
a
]
23 ꢀ18.0 (c 1.0, CHCl3); IR: nmax 1714 cmꢀ1; 1H NMR
D
d
8.10 (d, J¼7.5 Hz, 2H), 7.56 (t, J¼7.5 Hz,1H), 7.44
4.1.20. (1S,3R,4aS,5S,8aS)-4a-Hydroxy-3-isopropenyl-5,8a-dimethyl-
1,2,3,4,4a,5,8,8a-octahydro-1-naphthalenyl 4-nitrobenzoate 31. To
a stirred DCM (3 mL) solution of the alcohol (þ)-30 (10 mg,
0.05 mmol) were added Et3N (0.03 mL, 0.20 mmol), catalytic
amount of DMAP, and p-nitrobenzoyl chloride (17 mg, 0.09 mmol)
at room temperature for 10 h. The reaction was diluted with DCM
and washed with water, bicarbonate solution, and brine. The
crude material was subjected to silica gel chromatography (2%
EtOAc/hexane) to furnish 14 mg of 31 (88%); 1H NMR (300 MHz,
CDCl3): d 166.1,132.9,130.5,129.7 (2C),128.4 (2C),126.0,123.2, 82.6,
82.0, 74.0, 43.0, 42.7, 38.1, 36.8, 33.2, 30.7, 30.4, 25.1, 24.7; HRMS
(ES): m/z calcd for
349.1789.
C
21H26O3Na (MþþNa): 349.1780; found:
4.1.16. Synthesis of (þ)-28 and (þ)-29. Grignard reagent was pre-
pared by the drop wise addition of the 3-chloro-1-butene (1 mL,
10 mmol) in dry THF (7.5 mL) through an addition funnel to
a stirred suspension of the magnesium turnings (250 mg, 10 mmol)
with catalytic amount of iodine in dry THF (1.5 mL) at room
temperature. After the complete addition of the 3-chloro-1-
butene, the reaction was allowed to stir for another 30 min. The
CDCl3):
d
8.26 (d, J¼9.0 Hz, 2H), 8.13 (d, J¼9.0 Hz, 2H), 5.70e5.61
(m, 1H), 5.38e5.34 (m, 1H), 5.19 (s, 1H), 5.07 (s, 1H), 4.86 (s, 1H),
2.59e2.45 (m, 4H), 2.31e2.20 (m, 1H), 2.18e2.10 (m, 1H),
1.79e1.76 (m, 1H), 1.72 (s, 3H), 1.51e1.44 (m, 1H), 1.16 (s, 3H), 1.13
(d, J¼7.2 Hz, 3H).
4.1.21. Crystallographic information of 31. The compound was
crystallized from hexane. Mf¼C22H27O5N, MW¼385.5, colorless
crystal, crystal system: orthorhombic, space group: P212121, cell
freshly prepared
1 M solution of Grignard reagent (4 mL,
4.0 mmol) was added drop wise to a solution of the ketone (þ)-24
(500 mg, 1.60 mmol) in dry THF (5 mL) at ꢀ78 ꢁC and allowed to
stir for 1 h. The reaction was quenched with saturated NH4Cl and
diluted with ether (80 mL). The organic extract was washed with
water, 10% HCl, brine and dried over anhydrous Na2SO4. The crude
material was loaded on a silica gel column and elution with 8%
EtOAc/hexane delivered 203 mg of diene (þ)-28 and further elu-
tion with 10% EtOAc/hexane afforded 101 mg of diene (þ)-29 in
a ratio of 2:1, respectively (72%).
ꢀ
parameters: a¼7.5587 (21), b¼13.0083 (36), c¼20.3969 (57) A,
3
ꢀ
V¼2005.54 (10) A , Z¼4, rcalcd¼1.28
g
cmꢀ3
,
F(000)¼823.9,
m
¼0.090 mmꢀ1, Total no. of l.s. parameters¼350, R1¼0.108 for 3262
reflections with Fo>4s(Fo) and 0.130 for all 15,596 reflections.
wR2¼0.186, GOF¼1.411, restrained GOF¼1.411 for all data (CCDC
602354).
4.1.22. (1S,4aS,5S,8aS)-5,8a-Dimethyl-3-(1-methylethylidene)-
1,2,3,4,4a,5,8,8a-octahydro-1,4a-naphthalenediol 33. To an ice-
cooled solution of (þ)-30 (10 mg, 0.04 mmol) in dry THF (2 mL)
was added TfOH (0.01 mL, 0.13 mmol) and stirred for 1 h. The re-
action was quenched by the addition of few drops of water and
diluted with ethyl acetate (10 mL). The organic extract was washed
4.1.17. (1S,2S,3S,5R)-2-Allyl-5-isopropenyl-2-methyl-1-[(1S)-1-
24
methyl-2-propenyl] cyclohexane-1,3-diol (þ)-24. [
CHCl3); IR (neat): nmax 3445 cmꢀ1
6.27e6.07 (m, 2H), 5.17e4.99 (m, 4H), 4.79 (s, 1H), 4.76 (s, 1H),
a
]
þ22.8 (c 5.2,
D
;
1H NMR (300 MHz, CDCl3):
d

1726
R. Senthil Kumaran, G. Mehta / Tetrahedron 71 (2015) 1718e1731
with water (2 mL), bicarbonate solution (4 mL), and brine. The
crude material was charged on a silica gel column (12% EtOAc/
hexane) to furnish 6 mg of 33 (60%); IR (neat): nmax 3364 cmꢀ1; 1H
of water. The organic extract was washed successively with water
(2 mL), saturated sodium bicarbonate solution (4 mL), and brine.
The crude material was purified through a silica gel column chro-
NMR (300 MHz, CDCl3):
d
5.77e5.70 (m, 1H), 5.35e5.29 (m, 1H),
matography (2% EtOAc/hexane) to furnish 30 mg of benzoate
25
3.50 (td, J¼9.6, 3.0 Hz, 1H), 3.32 (d, J¼9.6 Hz, eOH), 2.87e2.79 (m,
3H), 2.30e2.19 (m, 2H), 1.88 (d, J¼14.4 Hz, 1H), 1.75 (s, 6H),
1.57e1.50 (m, 1H), 1.01 (d, J¼7.5 Hz, 3H), 1.00 (s, 3H); 13C NMR
(ꢀ)-37 (83%) as a colorless liquid; [
a]
ꢀ58.3 (c 2.3, CHCl3); IR
D
(neat): nmax 3583, 1719 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d 7.93 (d,
J¼7.5 Hz, 2H), 7.53 (t, J¼7.5 Hz, 1H), 7.41 (t, J¼7.5 Hz, 2H), 5.57 (s,
2H), 5.11 (t, J¼3.0 Hz, 1H), 5.07 (s, 1H), 4.86 (s, 1H), 3.34 (s, eOH),
2.66e2.51 (m, 3H), 2.24e2.15 (m, 4H), 1.78 (s, 3H), 1.46e1.43 (m,
1H), 1.18 (s, 3H), 1.11 (d, J¼7.8 Hz, 3H); 13C NMR (75 MHz, CDCl3):
(75 MHz, CDCl3):
d 129.8, 128.4, 125.9, 123.2, 77.2, 76.8, 39.8, 37.3,
34.4, 33.5, 31.3, 22.0, 20.4, 20.3, 12.8.
4.1.23. (1S,3R,4aS,5S,8aS)-4a-Hydroxy-3-isopropenyl-5,8a-dimethyl-
d 165.7, 148.3, 133.1, 130.2, 129.7, 129.6 (2C), 128.5 (2C), 122.8, 111.2,
1,2,3,4,4a,5,8,8a-octahydro-1-naphthalenyl
benzoate
78.6, 75.3, 42.8, 40.2, 36.5, 31.5, 31.1, 26.5, 23.3, 22.6, 15.9; HRMS
(þ)-34. Benzoylation of the secondary hydroxyl group in (þ)-30
(ES): m/z calcd for
C
22H28O3Na (MþþNa): 363.1936; found:
(25 mg, 0.11 mmol) was performed under the standard conditions
363.1925.
to produce the benzoate (þ)-34 (85%); [
a
]
25 þ42.8 (c 2.0, CHCl3); IR
D
(neat): nmax 3585, 1718 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d
7.95 (d,
4.1.27. (1S,2R,6S,7S,9R)-2,6,10,10-Tetramethyl-11-oxatricyclo
[7.2.1.01,6]dodec-3-en-7-yl benzoate (ꢀ)-38. To a solution of the
benzoate (ꢀ)-37 (15 mg, 0.04 mmol) in dry THF (2 mL) was added
TfOH (0.01 mL, 0.10 mmol) at 0 ꢁC and stirred for 1 h. The reaction
was quenched by the addition of small amount of water and diluted
with ethyl acetate (10 mL). The organic layer was washed with
water (3 mL), bicarbonate solution (3 mL), and brine. The crude
material was purified through a silica gel column (2% EtOAc/hex-
ane) to furnish 14 mg of (ꢀ)-38 (90%) as a solid; mp: 145e147 ꢁC;
J¼7.2 Hz, 2H), 7.55 (t, J¼7.2 Hz, 1H), 7.41 (t, J¼7.2 Hz, 2H), 5.63e5.58
(m, 1H), 5.35 (d, J¼10.2 Hz, 1H), 5.16 (s, 1H), 5.10 (s, 1H), 4.86 (s, 1H),
2.81 (br s, eOH), 2.59e2.46 (m, 4H), 2.20e2.13 (m, 2H), 1.78 (d,
J¼6.9 Hz, 1H), 1.72 (s, 3H), 1.47e1.41 (m, 1H), 1.15 (s, 3H), 1.13 (d,
J¼7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 165.9, 148.7, 133.1, 130.3,
129.8, 129.6 (2C), 128.4 (2C), 124.3, 111.0, 78.3, 73.9, 40.2, 38.2, 36.1,
31.4, 30.5, 26.5, 23.1, 22.3, 13.2; HRMS (ES): m/z calcd for
C
22H28O3Na (MþþNa): 363.1936; found: 363.1953.
[
a
]
22 ꢀ100.6 (c 1.7, CHCl3); IR: nmax 1708 cmꢀ1; 1H NMR (300 MHz,
D
4.1.24. (1S,2S,6S,7S,9R)-2,6,10,10-Tetramethyl-11-oxatricyclo
[7.2.1.01,6]dodec-3-en-7-yl benzoate (þ)-35. Cyclization reaction
was performed on the THF (2 mL) solution of benzoate (þ)-34
(15 mg, 0.04 mmol) in presence of TfOH (0.01 mL, 0.10 mmol) at
CDCl3):
d
8.10 (d, J¼7.2 Hz, 2H), 7.55 (t, J¼7.2 Hz, 1H), 7.43 (t,
J¼7.2 Hz, 2H), 5.64e5.54 (m, 2H), 5.12 (d, J¼7.8 Hz, 1H), 2.91e2.88
(m, 1H), 2.35e2.30 (m, 3H), 2.13e2.02 (m, 2H), 1.92 (d, J¼12.6 Hz,
1H), 1.54 (s, 3H), 1.51e1.48 (m, 1H), 1.29 (s, 3H), 1.19 (s, 3H), 1.12 (d,
0
ꢁC followed by usual workup. The crude material was charged
J¼8.1 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 166.1, 132.9, 130.5, 129.7
on a silica gel column (2% EtOAc/hexane) to furnish 12 mg of
(3C), 128.4 (2C), 123.6, 85.5, 82.2, 75.4, 43.7, 43.0, 42.0, 36.2, 33.2,
30.5, 30.3, 25.1, 24.5, 17.4; HRMS (ES): m/z calcd for C22H28O3Na
(MþþNa): 363.1936; found: 363.1941.
24
(þ)-35 (83%) as a crystalline solid; mp: 173e174 ꢁC; [
a
]
þ8.0 (c
D
1.0, CHCl3); IR: nmax 1706 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d 8.10
(d, J¼7.2 Hz, 2H), 7.55 (t, J¼7.2 Hz, 1H), 7.43 (t, J¼7.2 Hz, 2H),
5.63e5.58 (m, 1H), 5.38 (d, J¼9.9 Hz, 1H), 5.18 (d, J¼8.1 Hz, 1H),
2.91e2.88 (m, 1H), 2.38e2.28 (m, 3H), 2.18e1.95 (m, 2H), 1.62 (d,
J¼12.3 Hz, 1H), 1.57 (s, 3H), 1.50e1.47 (m, 1H), 1.27 (s, 3H), 1.17 (s,
4 .1. 2 8 . ( 1 S , 2 S , 3 R , 5 R ) - 1, 2 - D i a l l y l - 5 - i s o p r o p e n y l - 2 -
methylcyclohexane-1,3-diol (ꢀ)-40. A solution of the ketone (þ)-14
(650 mg, 3.1 mmol) in dry THF (8 mL) was added to an ice-cooled
suspension of the anhydrous CeCl3 (2.3 g, 9.3 mmol) in THF and the
reaction mixture allowed to stir for 10 min. The reaction was
cooled to ꢀ78 ꢁC and the freshly prepared 1 M solution of allyl
magnesium chloride (7.8 mL, 7.8 mmol) was added drop wise to
the reaction mixture and stirred at the same temperature for 1 h.
The reaction was quenched with saturated NH4Cl and diluted with
ether (75 mL). The organic extract was washed with water (10 mL),
10% HCl (15 mL), brine and dried over anhydrous Na2SO4. The
crude material was purified through a silica gel column (8% EtOAc/
3H), 1.10 (d, J¼6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 166.1,
132.9, 130.5, 130.0, 129.7 (2C), 128.4 (2C), 124.6, 84.3, 82.5, 74.4,
44.2, 42.2, 34.6, 34.1, 33.2, 30.7, 29.9, 25.2, 24.9, 14.3; HRMS
(ES): m/z calcd for C22H28O3Na (MþþNa): 363.1936; found:
363.1929.
4.1.25. (1S,3R,4aS,5R,8aS)-3-Isopropenyl-5,8a-dimethyl-
1,2,3,4,4a,5,8,8a-octahydro-1,4a-naphthalenediol (ꢀ)-36. A solution
of diene (þ)-29 (80 mg, 0.30 mmol) in dry degassed C6H6 (4 mL)
was exposed to Grubbs’ first generation catalyst (25 mg,
0.03 mmol) and stirred at room temperature for 3 h. The solvent
was removed under reduced pressure and the reaction mixture was
directly loaded on a silica gel column (10% EtOAc/hexane) to afford
hexane) to obtain 703 mg of (ꢀ)-40 (90%); mp: 58e59 ꢁC;
22
[a
]
ꢀ17.8 (c 2.7, CHCl3); IR: nmax 3332, 1640 cmꢀ1
;
1H NMR
D
(300 MHz, CDCl3):
d 5.95e5.70 (m, 2H), 5.21e5.01 (m, 4H), 4.74 (s,
2H), 3.71 (s, 1H), 3.13e3.09 (m, 1H), 2.61 (t, J¼13.2 Hz, 1H), 2.39
50 mg of (ꢀ)-36 (70%); mp: 119.5e120 ꢁC; [
a
]
D
21 ꢀ97.0 (c 1.0, CHCl3);
(dd, J¼13.2, 7.5 Hz, 1H), 2.22e2.01 (m, 3H), 1.74 (s, 3H), 1.71e1.52
IR: nmax 3378 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d
5.72e5.67 (m,1H),
(m, 3H), 1.20 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 149.3, 133.7,
5.53 (td, J¼10.2, 3.0 Hz, 1H), 5.22 (s, 1H), 4.88 (s, 1H), 3.45 (td, J¼9.0,
3.0 Hz, 1H), 3.32 (d, J¼8.7 Hz, 1H), 2.90e2.88 (m, 1H), 2.58 (br s,
eOH), 2.47e2.44 (m, 1H), 2.17e1.99 (m, 4H), 1.91 (s, 3H), 1.51e1.48
(m, 1H), 1.08 (d, J¼7.5 Hz, 3H), 1.01 (s, 3H); 13C NMR (75 MHz,
133.2, 119.7, 117.8, 109.0, 77.1, 74.9, 42.2, 40.7, 40.1, 37.1, 33.2, 33.1,
21.0, 17.1; HRMS (ES): m/z calcd for
C
16H26O2Na (MþþNa):
273.1830; found: 273.1837.
CDCl3):
d
150.0, 129.4, 124.3, 110.0, 77.2, 76.7, 44.6, 39.5, 36.6, 31.6,
4.1.29. (1R,3R,4aS,8aS)-3-Isopropenyl-8a-methyl-1,2,3,4,4a,5,8,8a-
octahydro-1,4a-naphthalenediol (þ)-41. A solution of diene (ꢀ)-40
(670 mg, 2.7 mmol) in dry degassed C6H6 (8 mL) was added to
Grubbs’ first generation catalyst (110 mg, 0.14 mmol) at room
temperature and allowed to reflux for 2 h. The solvent was removed
under reduced pressure and the reaction mixture was directly
charged on a silica gel column (15% EtOAc/hexane) to afford 565 mg
of (þ)-41 (95%) as a crystalline solid; mp: 100.5e101.5 ꢁC;
30.8, 28.9, 23.6, 22.9, 16.1; HRMS (ES): m/z calcd for C15H24O2Na
(MþþNa): 259.1674; found: 259.1699.
4.1.26. (1S,3R,4aS,5R,8aS)-4a-Hydroxy-3-isopropenyl-5,8a-dimethyl-
1,2,3,4,4a,5,8,8a-octahydro-1-naphthalenyl benzoate (ꢀ)-37. To
a dry DCM (3 mL) solution of the alcohol (ꢀ)-36 (25 mg, 0.11 mmol)
were added Et3N (0.07 mL, 0.53 mmol), catalytic amount of DMAP
(4 mg), and BzCl (0.04 mL, 0.32 mmol) at 0 ꢁC. The reaction was
stirred at room temperature for 10 h and quenched by the addition
[
a
]
22 þ34.6 (c 4.3, CHCl3); IR: nmax 3280 cmꢀ1; 1H NMR (300 MHz,
D
CDCl3): d 5.56e5.53 (m, 2H), 4.73 (s, 2H), 3.63 (s, 1H), 2.74e2.72 (m,

R. Senthil Kumaran, G. Mehta / Tetrahedron 71 (2015) 1718e1731
1727
1H), 2.34e2.28 (m, 1H), 2.19e2.13 (m, 1H), 1.98e1.91 (m, 1H),
1.84e1.82 (m, 2H), 1.74 (s, 3H), 1.70e1.59 (m, 2H), 1.45 (dd, J¼13.5,
31.3, 20.9, 17.9; HRMS (ES): m/z calcd for C21H26O3Na (MþþNa):
349.1780; found: 349.1785.
3.6 Hz, 1H), 1.15 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 149.2, 124.1,
123.4, 109.0, 77.1, 74.1, 39.0, 38.8, 38.7, 35.8, 34.2, 33.9, 21.1, 18.7;
HRMS (ES): m/z calcd for C14H22O2Na (MþþNa): 245.1517; found:
245.1525.
4.1.34. (1S,3R,8aR)-3-Isopropenyl-8a-methyl-1,2,3,5,8,8a-hexahy-
dro-1-naphthalenyl benzoate (þ)-45. Dehydration of (þ)-44
(220 mg, 0.68 mmol) was conducted under the same conditions,
described earlier and the purification of the crude reaction mixture
4.1.30. Crystallographic information of (þ)-41. The compound was
crystallized from hexane/DCM solvent system. Mf¼C14H22O2,
MW¼222.32, colorless crystal, crystal system: orthorhombic, space
group: P212121, cell parameters: a¼6.7810 (40), b¼8.2778 (49),
delivered 168 mg of triene (þ)-45 (81%) as a colorless liquid;
20
[a
]
þ129.1 (c 5.4, CHCl3); IR (neat): nmax 1718 cmꢀ1
;
1H NMR
D
(300 MHz, CDCl3):
d
8.06 (d, J¼7.8 Hz, 2H), 7.57 (t, J¼6.9 Hz, 1H),
7.46 (t, J¼7.5 Hz, 2H), 5.69 (s, 2H), 5.33 (s, 1H), 5.20 (dd, J¼12.3,
3.3 Hz, 1H), 4.78 (s, 1H), 4.74 (s, 1H), 3.05e2.94 (m, 2H), 2.60e2.58
(m, 1H), 2.53e2.50 (m, 1H), 2.17e2.15 (m, 1H), 2.03e1.99 (m, 1H),
1.71 (s, 3H), 1.66e1.62 (m, 1H), 1.19 (s, 3H); 13C NMR (75 MHz,
3
c¼22.5066 (14) A, V¼1263.34 (13) A , Z¼4, rcalcd¼1.17 g cmꢀ3
,
ꢀ
ꢀ
F(000)¼487.9,
m
¼0.076 mmꢀ1, Total no. of l.s. parameters¼149,
R1¼0.043 for 1999 reflections with Fo>4
s(Fo) and 0.047 for all 2147
reflections. wR2¼0.116, GOF¼0.999, restrained GOF¼0.999 for all
CDCl3): d 166.2, 147.9, 139.8, 132.9, 130.6, 129.5 (2C), 128.3 (2C),
data (CCDC 282317).
126.4, 125.4, 122.2, 110.2, 78.8, 42.8, 38.6, 35.4, 32.6, 30.4, 22.7, 20.2;
HRMS (ES): m/z calcd for C21H24O2Na (MþþNa): 331.1674; found:
331.1687.
4.1.31. (3S,4aS,8aR)-4a-Hydroxy-3-isopropenyl-8a-methyl-
1,2,3,4,4a,5,8,8a-octahydro-1-naphthalenone (ꢀ)-42. To a solution
of the diol (þ)-41 (550 mg, 2.5 mmol) in DCM (5 mL) were added
4.1.35. (1S,3R,8aR)-3-(1-Hydroxy-1-methylethyl)-8a-methyl-
ꢁ
ꢀ
PCC (1.3 g, 6.0 mmol) and 4 A mol. sieves at 0 C. The reaction was
1,2,3,5,8,8a-hexahydro-1-naphthalenyl
benzoate
stirred at room temperature for 1 h and on purification (10% EtOAc/
(þ)-46. Oxymercuration and demercuration reaction on the triene
(þ)-45 (155 mg, 0.50 mmol) delivered the crude material and
chromatographic purification eventually furnished (þ)-46 (76%);
hexane) furnished 475 mg of ketone (ꢀ)-42 (87%) as a colorless
22
solid; mp: 111e112 ꢁC; [
a
]
D
ꢀ73.8 (c 1.3, CHCl3); IR: nmax 3417,
1696 cmꢀ1
;
1H NMR (300 MHz, CDCl3):
d
5.67 (d, J¼11.4 Hz, 1H),
[a
]
21 þ77.9 (c 6.8, CHCl3); IR (neat): nmax 3421, 1719 cmꢀ1; 1H NMR
D
5.59 (d, J¼11.4 Hz, 1H), 4.79 (s, 1H), 4.76 (s, 1H), 2.93e2.85 (m, 1H),
2.67 (d, J¼13.2 Hz, 1H), 2.57 (d, J¼13.2 Hz, 1H), 2.39 (dd, J¼14.7,
4.8 Hz, 1H), 2.24e2.22 (m, 2H), 2.09 (t, J¼12.9 Hz, 1H), 1.97e1.94 (m,
1H), 1.76 (s, 3H), 1.64e1.61 (m, 1H), 1.12 (s, 3H); 13C NMR (75 MHz,
(300 MHz, CDCl3):
d
8.06 (d, J¼7.5 Hz, 2H), 7.58 (t, J¼7.5 Hz,1H), 7.46
(t, J¼7.5 Hz, 2H), 5.68 (s, 2H), 5.52 (s, 1H), 5.18 (dd, J¼12.0, 3.3 Hz,
1H), 2.99e2.96 (m, 1H), 2.61e2.59 (m, 1H), 2.52e2.40 (m, 2H),
2.18e2.16 (m, 1H), 2.03e2.00 (m, 1H), 1.29e1.26 (m, 1H), 1.23 (s,
CDCl3):
d
214.2, 147.3, 124.5, 122.7, 109.8, 75.1, 51.7, 41.1, 38.8, 38.7,
3H), 1.18 (s, 3H), 1.17 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 166.3,
37.7, 36.9, 20.6, 14.5; HRMS (ES): m/z calcd for C14H20O2Na
141.4, 132.9, 130.6, 129.5 (2C), 128.4 (2C), 126.5, 125.4, 119.4, 79.0,
72.4, 46.3, 38.6, 35.5, 32.9, 27.9, 26.8, 25.9, 22.6; HRMS (ES): m/z
calcd for C21H26O3Na (MþþNa): 349.1780; found: 349.1811.
(MþþNa): 243.1361; found: 243.1391.
4.1.32. (1S,3R,4aS,8aS)-3-Isopropenyl-8a-methyl-1,2,3,4,4a,5,8,8a-
octahydro-1,4a-naphthalenediol (þ)-43. To a stirred solution of the
ketone (ꢀ)-42 (480 mg, 2.2 mmol) in MeOH (5 mL) was added
NaBH4 (84 mg, 2.2 mmol) at 0 ꢁC and reaction was allowed to stir at
the same temperature for 45 min. The reaction was quenched with
water and the solvent was removed under reduced pressure. The
mixture was extracted with ethyl acetate (60 mL) and washed with
water (5 mL), brine and dried. The crude material was charged on
a silica gel column (20% EtOAc/hexane for (þ)-41 and 25% EtOAc/
4.1.36. Synthesis of (þ)-48 and (þ)-47. To a DCM (3 mL) solution of
the diene (þ)-46 (100 mg, 0.31 mmol) were added mCPBA (76 mg,
0.31 mmol) and NaHCO3 (26 mg, 0.31 mmol) at 0 ꢁC and allowed to
stir for 1 h. The reaction mixture was quenched with saturated
solution of sodium sulfite and diluted with DCM (30 mL). The or-
ganic extract was washed with water (3 mL), bicarbonate solution
(5 mL), and brine, respectively. The concentrated crude material
was loaded on a silica gel column first eluting with 18% EtOAc/
hexane to obtain 70 mg of (þ)-48 and then with 20% EtOAc/hexane
to furnish 18 mg of (þ)-47 in a ratio of 4:1 (83%).
hexane for (þ)-43) to obtain 276 mg of (þ)-41 and 184 mg of (þ)-43
22
(95%) in a ratio of 1.5:1; [
a
]
þ52.8 (c 1.1, CHCl3); IR (neat): nmax
D
3428, 1644 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d 5.57 (s, 2H), 4.72 (s,
2H), 4.01e3.97 (m, 1H), 2.57e2.48 (m, 1H), 2.32e2.23 (m, 2H),
2.04e1.98 (m, 1H), 1.91e1.86 (m, 2H), 1.73 (s, 3H), 1.57e1.44 (m, 1H),
1.38e1.26 (m, 1H), 1.16e1.12 (m, 1H), 1.10 (s, 3H); 13C NMR (75 MHz,
4.1.37. (1aS,2R,4S,4aS,8aR)-2-(1-Hydroxy-1-methylethyl)-4a-
methyl-2,3,4,4a,5,8-hexa hydro-1aH-naphtho[1,8a-b]oxiren-4-yl
24
benzoate (þ)-48. [
a]
þ64.9 (c 2.9, CHCl3); IR (neat): nmax 3478,
D
CDCl3):
d
148.8, 124.2, 123.4, 108.9, 73.4, 73.2, 40.9, 39.5, 38.5, 37.3,
1717 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d
8.02 (d, J¼7.2 Hz, 2H), 7.56
35.0, 30.0, 20.9, 17.7; HRMS (ES): m/z calcd for C14H22O2Na
(t, J¼7.2 Hz, 1H), 7.44 (t, J¼7.2 Hz, 2H), 5.75e5.63 (m, 2H), 5.18 (dd,
J¼12.3, 4.2 Hz, 1H), 3.19 (s, 1H), 2.70e2.68 (m, 1H), 2.65e2.62 (m,
1H), 2.27e2.16 (m, 2H),1.86e1.73 (m, 2H),1.56e1.44 (m,1H),1.28 (s,
(MþþNa): 245.1517; found: 245.1538.
4.1.33. (1S,3R,4aS,8aS)-4a-Hydroxy-3-isopropenyl-8a-methyl-
3H), 1.24 (s, 3H), 1.20 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 166.0,
1,2,3,4,4a,5,8,8a-octahydro-1-naphthalenyl
benzoate
132.9,130.4,129.5 (2C), 128.4 (2C), 124.9, 123.8, 75.6, 72.1, 65.1, 63.3,
(þ)-44. Benzoylation of the secondary hydroxyl group (þ)-43
(180 mg, 0.81 mmol) was performed under the standard conditions
as described above. The crude material was purified through col-
45.3, 36.3, 31.8, 31.4, 28.5, 25.5, 24.8, 19.5; HRMS (ES): m/z calcd for
C
21H26O4Na (MþþNa): 365.1729; found: 365.1745.
umn chromatography (2% EtOAc/hexane) to furnish 240 mg of
4.1.38. (1aS,2aR,3S,5R,7aR)-5-(1-Hydroxy-1-methylethyl)-2a-
methyl-1a,2,2a,3,4,5,7,7a-octahydronaphtho[2,3-b]oxiren-3-yl ben-
21
benzoate (þ)-44 (90%); [
a]
þ73.9 (c 1.4, CHCl3); IR (neat): nmax
D
3513, 1716, 1644 cmꢀ1
;
1H NMR (300 MHz, CDCl3):
d
8.05 (d,
zoate (þ)-47. [
a
]
þ63.1 (c 1.3, CHCl3); IR (neat): nmax 3440,
24
D
J¼8.4 Hz, 2H), 7.56 (t, J¼8.1 Hz, 1H), 7.45 (t, J¼8.4 Hz, 2H), 5.64 (d,
J¼14.4 Hz, 1H), 5.59 (d, J¼14.4 Hz, 1H), 5.45 (dd, J¼11.4, 4.8 Hz, 1H),
4.73 (s, 2H), 2.71e2.53 (m, 2H), 2.36e2.30 (m, 1H), 2.13e2.07 (m,
3H), 1.74 (s, 3H), 1.68e1.57 (m, 2H), 1.46e1.42 (m, 1H), 1.05 (s. 3H);
1715 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d
8.05 (d, J¼7.2 Hz, 2H), 7.59
(t, J¼7.2 Hz, 1H), 7.47 (t, J¼7.2 Hz, 2H), 5.56 (s, 1H), 5.06 (dd, J¼12.0,
3.6 Hz, 1H), 3.27 (s, 1H), 3.25e3.22 (m, 1H), 2.82e2.77 (m, 1H),
2.59e2.56 (m, 1H), 2.38e2.34 (m, 1H), 2.22e2.19 (m, 1H), 2.06e1.95
13C NMR (75 MHz, CDCl3):
d
166.1, 148.4, 132.8, 130.7, 129.5 (2C),
(m, 2H), 1.76e1.62 (m, 1H), 1.23 (s, 3H), 1.18 (s, 3H), 1.16 (s, 3H); 13
C
128.3 (2C), 123.9, 123.7, 109.2, 76.7, 73.4, 40.5, 39.4, 38.4, 37.0, 31.6,
NMR (75 MHz, CDCl3):
d 166.1, 137.6, 133.0, 130.4, 129.5 (2C), 128.4

1728
R. Senthil Kumaran, G. Mehta / Tetrahedron 71 (2015) 1718e1731
(2C), 124.0, 78.3, 72.2, 53.8, 50.5, 46.0, 36.5, 33.5, 31.9, 27.9, 26.3,
25.9, 23.8.
3.75e3.73 (m, 1H), 3.42 (s, 1H), 3.06 (d, J¼6 Hz, 1H), 2.63e2.57 (m,
2H), 2.39 (dd, J¼13.8, 5.1 Hz, 1H), 2.14e2.06 (m, 1H), 1.77 (s, 3H),
1.76e1.61 (m, 2H), 1.27 (s, 3H), 1.08 (d, J¼6.9 Hz, 3H); 13C NMR
4.1.39. (1S,6S,7S,9R,12S)-12-Hydroxy-6,10,10-trimethyl-11-
oxatricyclo [7.2.1.01,6]dodec-3-en-7-yl benzoate (ꢀ)-49. Lewis acid
mediated cyclization was performed on the epoxide (þ)-48 (60 mg,
0.18 mmol) in ice-cooled DCM solution (4 mL), under the standard
BF3$OEt2 conditions (0.02 mL, 0.20 mmol). The reaction was
quenched with water and diluted with DCM. The organic extract
was successively washed with water (3 mL), bicarbonate solution
(3 mL), and brine then dried over anhydrous Na2SO4. The crude
material was purified through silica gel column chromatography
(75 MHz, CDCl3): d 149.5, 142.4, 134.0, 117.5, 114.4, 109.1, 78.7, 76.1,
45.2, 43.6, 40.9, 35.1, 33.3, 32.9, 21.1, 18.7, 17.2; HRMS (ES): m/z calcd
for C17H28O2Na (MþþNa): 287.1987; found: 287.2000.
4.1.44. (1R,3R,4aR,5S,8aS)-3-Isopropenyl-5,8a-dimethyl-
1,2,3,4,4a,5,8,8a-octahydro-1,4a-naphthalenediol (þ)-53. A solution
of diene (ꢀ)-51 (2.18 g, 8.3 mmol) in dry C6H6 (15 mL) was exposed
to Grubbs’ first generation catalyst (470 mg, 0.6 mmol) at room
temperature and the reaction mixture was refluxed for 3 h. The
solvent was removed under vacuum and the reaction mixture was
(20% EtOAc/hexane) to afford 55 mg of (ꢀ)-49 (92%) as a colorless
25
solid; mp: 205e206 ꢁC; [
a]
ꢀ4.1 (c 1.4, CHCl3); IR: nmax 3340,
directly loaded on a silica gel column (25% EtOAc/hexane) to afford
D
23
1714 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d
8.08 (d, J¼7.2 Hz, 2H), 7.57
1.73 g of (þ)-53 (89%); [
a]
þ75.9 (c 0.8, CHCl3); IR (neat): nmax
D
(t, J¼7.2 Hz, 1H), 7.45 (t, J¼7.2 Hz, 2H), 5.69e5.58 (m, 2H), 5.28 (d,
J¼8.7 Hz, 1H), 4.44 (s, 1H), 2.89e2.86 (m, 1H), 2.83e2.74 (m, 1H),
2.65e2.63 (m, 1H), 2.02e1.91 (m, 3H), 1.56 (s, 3H), 1.49e1.46 (m,
3344 cmꢀ1 1H NMR (300 MHz, CDCl3):
; d 5.47 (br s, 1H), 5.36 (d,
J¼9.9 Hz,1H), 4.74 (s, 2H), 3.63 (br s, 1H), 3.09 (d, J¼6.6 Hz,1H), 2.97
(s, 1H), 2.68e2.65 (m, 1H), 2.45e2.42 (m, 1H), 2.19e2.17 (m, 1H),
1.84e1.81 (m, 2H), 1.75 (s, 3H), 1.27 (t, J¼12.6 Hz, 1H), 1.16 (s, 3H),
1H), 1.33 (s, 6H); 13C NMR (75 MHz, CDCl3):
d 166.2, 132.9, 130.6,
129.6 (2C), 128.4 (2C), 126.8, 123.2, 80.0, 78.0, 76.8, 73.8, 46.3, 42.5,
1.00 (d, J¼7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 149.5, 130.6,
35.1, 33.6, 31.1, 27.3, 25.7, 25.3; HRMS (ES): m/z calcd for
122.8, 109.1, 77.4, 76.1, 39.2, 38.5, 36.1, 33.9, 33.5, 31.9, 21.0, 18.8,
13.2; HRMS (ES): m/z calcd for C15H24O2Na (MþþNa): 259.1674;
found: 259.1683.
C
21H26O4Na (MþþNa): 365.1729; found: 365.1749.
4.1.40. Crystallographic information of (ꢀ)-49. The compound was
crystallized from DCM solvent system. Mf¼C21H26O4, MW¼342.4,
colorless crystal, crystal system: orthorhombic, space group:
4.1.45. (1R,3R,4aR,5S,8aS)-4a-Hydroxy-3-isopropenyl-5,8a-di-
methyl-1,2,3,4,4a,5,8,8a-octahydro-1-naphthalenyl 4-nitrobenzoate
54. p-Nitrobenzoyl derivative of (þ)-53 (25 mg, 0.11 mmol) was
prepared by following the previously adapted procedure on (þ)-76
and the resultant crude material was purified to obtain 36 mg of 94
P212121,
cell
parameters:
a¼8.9682(35),
b¼10.3295(40),
3
c¼19.8038(76) A, V¼1834.57(12) A , Z¼4, rcalcd¼1.24 g cmꢀ3
,
ꢀ
ꢀ
F(000)¼735.9,
m
¼0.085 mmꢀ1, Total no. of l.s. parameters¼330,
R1¼0.046 for 2417 reflections with Fo>4
s
(Fo) and 0.087 for all
(85%); 1H NMR (300 MHz, CDCl3):
d
8.30 (d, J¼7.8 Hz, 2H), 8.20 (d,
14,717 reflections. wR2¼0.067, GOF¼0.947, restrained GOF¼0.947
J¼7.8 Hz, 2H), 5.50 (d, J¼9.9 Hz, 1H), 5.42 (d, J¼9.9 Hz, 1H), 5.18 (s,
1H), 4.77 (s, 1H), 4.75 (s, 1H), 2.64e2.52 (m, 3H), 2.34e2.31 (m, 1H),
2.04e1.85 (m, 3H), 1.74 (s, 3H), 1.45e1.29 (m, 1H), 1.10 (s, 3H), 1.08
(d, J¼9.0 Hz, 3H).
for all data (CCDC 602353).
4.1.41. Synthesis of (ꢀ)-50 and (ꢀ)-51. The Grignard reagent de-
rived from 3-chloro-1-butene was prepared by following the pre-
viously adapted procedure. To the ice-cooled suspension of the
anhydrous CeCl3 (10.3 g, 42.0 mmol) in THF was added the ketone
(þ)-14 (2.9 g, 14.0 mmol) in dry THF (20 mL) and the reaction
mixture was allowed to stir for 10 min. After that the reaction was
cooled to ꢀ78 ꢁC and now the freshly prepared 1.2 M Grignard
solution (29 mL, 35 mmol) was added drop wise to the reaction
mixture over a period of 15 min. The stirring was continued for 1 h
at the same temperature. Once the starting material disappeared as
detected by the TLC, the reaction was quenched with saturated
NH4Cl and further extracted with ether (150 mL). The organic ex-
tract was washed with water (20 mL), 10% HCl (25 mL), brine
(30 mL) and dried over anhydrous Na2SO4. The crude material was
charged on a silica gel column, first eluting with 6% EtOAc/hexane
to furnish 1.58 g of (ꢀ)-50 and then with 8% EtOAc/hexane to de-
liver 1.93 g of (ꢀ)-51 (95%) in the ratio of (1:1.2).
4.1.46. Crystallographic information of 54. The compound was
crystallized from hexane/DCM solvent system. Mf¼C22H27O5N,
MW¼385.45, Crystal system: monoclinic, space group: P2(1), cell
ꢀ
parameters: a¼8.265 (2), b¼13.123 (3), c¼18.829 (5) A,
b
¼94.113
(5), V¼2037.09 (6) A , Z¼4, rcalcd¼1.257 g cmꢀ3, F(000)¼824.0,
3
ꢀ
m
¼0.09 mmꢀ1, T¼293 K; Total number of l.s. Parameters¼721,
R1¼0.0576 for 6673 Fo>4
s(Fo) and 0.0797 for all 8820 data.
wR2¼0.1213, GOF¼1.123, Restrained GOF¼1.123 for all data. Crys-
tallographic data (without structure factor) have deposited in the
Cambridge Crystallographic Data Center. CCDC depository number
is CCDC 214302.
4.1.47. (1R,3R,4aR,5R,8aS)-3-Isopropenyl-5,8a-dimethyl-
1,2,3,4,4a,5,8,8a-octahydro-1,4a-naphthalenediol (ꢀ)-55. A solution
of diene (ꢀ)-50 (1.88 g, 7.1 mmol) in dry degassed C6H6 (12 mL) was
added to Grubbs’ first generation catalyst (290 mg, 0.35 mmol) at
room temperature and allowed to reflux at 80 ꢁC for 2.5 h. The
solvent was removed under reduced pressure and directly purified
4.1.42. (1R,2S,3R,5R)-2-Allyl-5-isopropenyl-2-methyl-1-[(1R)-1-
methyl-2-propenyl] cyclohexane-1,3-diol (ꢀ)-50. Mp: 76.5e77.5 ꢁC;
22
[
a
]
ꢀ10.4 (c 1.3, CHCl3); IR: nmax 3337 cmꢀ1
;
1H NMR (300 MHz,
through column chromatography (20% EtOAc/hexane) to afford
D
22
CDCl3):
d
5.99e5.71 (m, 2H), 5.08e5.02 (m, 4H), 4.77 (s, 2H),
1.60 g of (ꢀ)-55 (95%); [
a]
ꢀ66.2 (c 0.8, CHCl3); IR (neat): nmax
D
3.69e3.67 (m, 1H), 3.49e3.46 (s, eOH), 2.99 (s, eOH), 2.68e2.51
(m, 2H), 2.23e2.21 (m, 2H), 1.78 (s, 3H), 1.72e1.59 (m, 4H), 1.26 (s,
3321 cmꢀ1 1H NMR (300 MHz, CDCl3):
; d 5.63e5.60 (m, 1H),
5.48e5.46 (m, 1H), 4.73 (s, 2H), 3.56e3.54 (m, 1H), 3.07 (br s, 2H),
2.75e2.72 (m, 1H), 2.18e2.12 (m, 2H), 1.81 (d, J¼6.9 Hz, 2H), 1.74 (s,
3H), 1.46 (dd, J¼8.7, 3.3 Hz, 1H), 1.21 (s, 3H), 1.15 (d, J¼7.5 Hz, 3H);
3H), 1.07 (d, J¼6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 149.6, 142.0,
133.9, 117.6, 115.3, 109.0, 78.4, 75.9, 44.9, 43.7, 40.5, 35.6, 33.1, 33.0,
21.1, 19.0, 17.4; HRMS (ES): m/z calcd for C17H28O2Na (MþþNa):
287.1987; found: 287.2015.
13C NMR (75 MHz, CDCl3):
d 149.2, 131.4, 121.0, 109.0, 78.5, 75.7,
43.5, 42.2, 39.3, 35.5, 34.0, 33.9, 21.1, 21.0, 16.0; HRMS (ES): m/z
calcd for C15H24O2Na (MþþNa): 259.1674; found: 259.1695.
4.1.43. (1R,2S,3R,5R)-2-Allyl-5-isopropenyl-2-methyl-1-[(1S)-1-
methyl-2-propenyl] cyclohexane-1,3-diol (ꢀ)-51. Mp: 70e72 ꢁC;
4.1.48. (3S,4aR,5R,8aR)-4a-Hydroxy-3-isopropenyl-5,8a-dimethyl-
1,2,3,4,4a,5,8,8a-octahydro-1-naphthalenone (ꢀ)-56. To a solution
of the diol (ꢀ)-55 (1.45 g, 6.15 mmol) in DCM (15 mL) was added
22
[
a
]
ꢀ9.2 (c 1.2, CHCl3); IR: nmax 3336 cmꢀ1
;
1H NMR (300 MHz,
d 5.99e5.69 (m, 2H), 5.08e4.94 (m, 4H), 4.77 (s, 2H),
D
CDCl3):

R. Senthil Kumaran, G. Mehta / Tetrahedron 71 (2015) 1718e1731
1729
ꢁ
ꢀ
PCC (3.31 g, 15.4 mmol) in portions and 4 A mol. sieves at 0 C and
d 166.1, 148.4, 132.8, 131.0, 130.7, 129.5 (2C), 128.3 (2C), 121.4, 109.1,
the reaction was allowed to stir for 1 h at room temperature. The
reaction mixture was diluted with DCM (10 mL), filtered through
a Celite pad, and concentrated under reduced pressure. The con-
centrated crude material was loaded on a silica gel column (12%
76.8, 74.7, 43.3, 41.6, 47.0, 37.1, 31.3, 30.9, 20.9, 18.6, 16.0; HRMS
(ES): m/z calcd for
C
22H28O3Na (MþþNa): 363.1936; found:
363.1941.
EtOAc/hexane) to furnish 1.12 g of ketone (ꢀ)-56 (78%) as a color-
4.1.52. (1S,3R,5R,8aR)-3-Isopropenyl-5,8a-dimethyl-1,2,3,5,8,8a-hex-
ahydro-1-naphthalenyl benzoate (þ)-59. Dehydration was per-
formed on (þ)-58 (205 mg, 0.61 mmol) in dry pyridine (3 mL) with
thionyl chloride (0.07 mL, 0.92 mmol) at ꢀ35 ꢁC. After 45 min, the
reaction was carefully quenched by the addition of few drops of
water and the pyridine was removed under reduced pressure. The
reaction mixture was extracted with ether (40 mL) and the ethe-
real extract was washed with dil HCl (4 mL), water (4 mL), and
brine. The organic extract was dried over anhydrous Na2SO4 and
concentrated under reduced pressure to obtain the crude yellow
oily liquid. The crude material was loaded on a silica gel column
22
less solid; mp: 138e139 ꢁC; [
a
]
ꢀ175.0 (c 0.6, CHCl3); IR: nmax
D
3413, 1694 cmꢀ1 1H NMR (300 MHz, CDCl3):
; d 5.70e5.66 (m, 1H),
5.57e5.56 (m, 1H), 4.78 (s, 1H), 4.76 (s, 1H), 2.93e2.84 (m, 1H),
2.69e2.56 (m, 2H), 2.41e2.30 (m, 2H), 2.11 (t, J¼12.6 Hz, 1H),
1.93e1.90 (m, 1H),1.76 (s, 3H),1.67e1.64 (m,1H),1.16 (s, 3H),1.15 (d,
J¼6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 214.3, 147.4, 131.5, 120.8,
109.9, 76.7, 52.5, 42.3, 40.9, 40.5, 38.9, 36.4, 20.6, 16.1, 15.3; HRMS
(ES): m/z calcd for
C
15H22O2Na (MþþNa): 257.1517; found:
257.1544.
4.1.49. Crystallographic information of (ꢀ)-56. The compound was
crystallized from hexane/DCM solvent system. Mf¼C15H22O2,
MW¼234.34, colorless crystal, Crystal system: monoclinic, space
group: P2(1), cell parameters: a¼10.305 (2), b¼10.916 (2), c¼12.805
(1% EtOAc/hexane) to deliver 155 mg of triene (þ)-59 (80%);
23
[a
]
þ31.7 (c 1.2, CHCl3); IR (neat): nmax 1718 cmꢀ1
;
1H NMR
D
(300 MHz, CDCl3):
d
8.05 (d, J¼8.4 Hz, 2H), 7.56 (t, J¼7.2 Hz, 1H),
7.45 (t, J¼7.8 Hz, 2H), 5.68e5.65 (m, 2H), 5.47 (s, 1H), 5.22 (dd,
J¼12.0, 3.9 Hz, 1H), 4.77 (s, 1H), 4.74 (s, 1H), 3.03e2.95 (m, 2H),
2.45e2.42 (m, 1H), 2.16e2.13 (m, 1H), 2.05e1.95 (m, 2H), 1.71 (s,
3H), 1.24 (d, J¼7.8 Hz, 3H), 1.24 (s, 3H); 13C NMR (75 MHz, CDCl3):
3
¼108.436 (4), V¼1366.75 (6) A , Z¼4, rcalcd¼1.139 g cmꢀ3
,
ꢀ
ꢀ
(3) A,
b
F(000)¼512.0,
m
¼0.07 mmꢀ1. Total number of l.s. parameters¼315,
R1¼0.0565 for 4301, Fo>4
s(Fo) and 0.0739 for all 5368 data.
wR2¼0.1254, GOF¼1.106, Restrained GOF¼1.106 for all data. Crys-
tallographic data (without structure factor) have deposited in the
Cambridge Crystallographic Data Center. CCDC depository number
is CCDC 214304.
d 166.3, 148.0, 144.6, 132.8, 132.0, 130.6, 129.6 (2C), 128.3 (2C),
124.8, 123.8, 110.3, 78.8, 42.2, 39.2, 38.8, 34.7, 30.3, 25.1, 21.7, 20.5;
HRMS (ES): m/z calcd for C22H26O2Na (MþþNa): 345.1830; found:
345.1848.
4.1.50. (1S,3R,4aR,5R,8aS)-3-Isopropenyl-5,8a-dimethyl-
1,2,3,4,4a,5,8,8a-octahydro-1,4a-naphthalenediol (ꢀ)-57. To a stir-
red solution of the ketone (ꢀ)-56 (1.10 g, 4.70 mmol) in MeOH
(8 mL) was added NaBH4 (180 mg, 4.70 mmol) at 0 ꢁC and reaction
was allowed to stir at the same temperature for 45 min. The re-
action was quenched with ice-cold water (5 mL) and solvent was
removed under reduced pressure. The reaction mixture was
extracted with ethyl acetate (100 mL) and washed with water,
brine. The crude material was charged on a silica gel column (20%
EtOAc/hexane for (ꢀ)-55 and 30% EtOAc/hexane for (ꢀ)-57) to
4.1.53. (1S,3R,5R,8aR)-3-(1-Hydroxy-1-methylethyl)-5,8a-dimethyl-
1,2,3,5,8,8a-hexahydro-1-naphthalenyl benzoate (ꢀ)-60. To a stirred
solution of triene (þ)-59 (140 mg, 0.44 mmol) in (3 mL) of THF/
water solution (4:1) was added mercuric acetate (135 mg,
0.44 mmol) along with catalytic amount of AcOH at room tem-
perature and stirred for 1 h. The reaction was quenched with few
drops of NaBH4 dissolved in 10% NaOH solution. The reaction
mixture was extracted with ethyl acetate (40 mL) and the organic
extract was washed with water (4 mL), brine and dried. The crude
material was charged on a silica gel column eluting with 22% EtOAc/
hexane to deliver 104 mg of (ꢀ)-60 (70%) as a crystalline solid; mp:
obtain 800 mg of (ꢀ)-55 and 198 mg of (ꢀ)-57 (90%) in a ratio of
22
(4:1); mp: 116e118 ꢁC; [
a
]
D
ꢀ50.0 (c 1.0, CHCl3); IR: nmax
146.5e147.5 ꢁC; [
a]
22 ꢀ4.2 (c 1.2, CHCl3); IR: nmax 3351, 1715 cmꢀ1
;
D
3449 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d
5.62e5.54 (m, 2H), 4.72 (s,
1H NMR (300 MHz, CDCl3):
d
8.06 (d, J¼8.1 Hz, 2H), 7.58 (t, J¼7.2 Hz,
2H), 3.96 (dd, J¼11.1, 4.5 Hz, 1H), 2.55 (t, J¼12.3 Hz, 1H), 2.26e2.14
1H), 7.46 (t, J¼7.8 Hz, 2H), 5.66 (s, 2H), 5.64 (s, 1H), 5.22 (dd, J¼12.3,
3.6 Hz, 1H), 2.97 (d, J¼6.9 Hz, 1H), 2.43e2.38 (m, 2H), 2.18 (dd,
J¼4.5, 3.6 Hz, 1H), 2.02e1.98 (m, 2H), 1.25 (d, J¼7.5 Hz, 3H), 1.23 (s,
(m, 2H), 1.89e1.82 (m, 2H), 1.73 (s, 3H), 1.67e1.26 (m, 3H), 1.17 (d,
J¼7.5 Hz, 3H), 1.13 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 148.9, 130.8,
121.7, 108.9, 75.0, 73.1, 43.4, 41.8, 41.5, 37.6, 35.0, 29.6, 20.9, 18.5,
16.0; HRMS (ES): m/z calcd for C15H24O2Na (MþþNa): 259.1674;
found: 259.1700.
3H), 1.23 (s, 3H), 1.17 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 166.4,
146.1, 132.9, 132.2, 130.6, 129.5 (2C), 128.4 (2C), 123.8, 122.1, 79.2,
72.4, 46.0, 39.7, 38.9, 34.9, 27.9, 27.1, 25.9, 24.8, 21.3; HRMS (ES): m/z
calcd for C22H28O3Na (MþþNa): 363.1936; found: 363.1970.
4.1.51. (1S,3R,4aR,5R,8aS)-4a-Hydroxy-3-isopropenyl-5,8a-dimethyl-
1,2,3,4,4a,5,8,8a-octahydro-1-naphthalenyl benzoate (þ)-58. To
a dry DCM (5 mL) solution of (ꢀ)-57 (180 mg, 0.76 mmol) were
added Et3N (0.43 mL, 3.1 mmol), catalytic amount of DMAP
(10 mg), and BzCl (0.27 mL, 2.3 mmol) at 0 ꢁC. The reaction mixture
was stirred at room temperature for 15 h and poured into ice-cold
water. The organic compound was extracted with DCM (50 mL)
and successively washed with water, sodium bicarbonate solution,
and brine. The crude material was purified through silica gel col-
umn chromatography (2% EtOAc/hexane) to obtain 225 mg of
4.1.54. Synthesis of 61 and 62. To a DCM (3 mL) solution of the
diene (ꢀ)-60 (40 mg, 0.12 mmol) were added mCPBA (30 mg,
0.12 mmol) and NaHCO3 (10 mg, 0.12 mmol) at 0 ꢁC and allowed to
stir for 1.5 h. The reaction mixture was quenched with saturated
solution of sodium sulfite and diluted with DCM (15 mL). The or-
ganic extract was washed with water (3 mL), bicarbonate solution
(5 mL), and brine, respectively. The concentrated crude material
was loaded on a silica gel column (25% EtOAc/hexane for 61 and
30% EtOAc/hexane for 62) to furnish 15 mg of 61 and 19 mg of 62
(83%) in a ratio of (4:5).
benzoate (þ)-58 (87%) as a colorless solid; mp: 135.5e136.5 ꢁC;
23
[
a]
þ33.8 (c 0.6, CHCl3); IR: nmax 3510, 1717 cmꢀ1
;
1H NMR
D
(300 MHz, CDCl3):
d
8.04 (d, J¼7.2 Hz, 2H), 7.56 (t, J¼7.5 Hz, 1H),
4.1.55. 61:
4a,8-dimethyl-2,3,4,4a,5,8-hexahydro-1aH-naphtho[1,8a-b]oxiren-4-
yl benzoate. 1H NMR (300 MHz, CDCl3):
(1aS,2R,4S,4aS,8R,8aR)-2-(1-Hydroxy-1-methylethyl)-
7.45 (t, J¼7.2 Hz, 2H), 5.66e5.59 (m, 2H), 5.45 (dd, J¼11.7, 5.1 Hz,
1H), 4.72 (s, 2H), 2.68 (t, J¼12.6 Hz, 1H), 2.57e2.54 (m, 1H),
2.18e1.94 (m, 3H), 1.73 (s, 3H), 1.68e1.41 (m, 1H), 1.47e1.42 (m,
2H), 1.19 (d, J¼7.5 Hz, 3H), 1.07 (s, 3H); 13C NMR (75 MHz, CDCl3):
d
8.02 (d, J¼7.5 Hz, 2H), 7.57
(t, J¼7.5 Hz, 1H), 7.49 (t, J¼7.5 Hz, 2H), 5.70 (br s, 2H), 5.14 (dd,
J¼12.3, 3.9 Hz, 1H), 3.14 (s, 1H), 2.60e2.57 (m, 1H), 2.23e2.05 (m,

1730
R. Senthil Kumaran, G. Mehta / Tetrahedron 71 (2015) 1718e1731
3H), 1.83e1.78 (m, 1H), 1.48e1.44 (m, 1H), 1.29 (s, 3H), 1.25 (s, 3H),
1.22 (s, 3H), 1.19 (d, J¼7.2 Hz, 3H).
(td, J¼9.0, 7.2 Hz, 1H), 3.87 (dd, J¼9.3, 6.9 Hz, 1H), 2.64e2.25 (m,
3H), 1.94e1.73 (m, 3H), 1.45 (s, 3H), 1.36 (s, 3H), 1.29 (d, J¼6.6 Hz,
3H), 1.17 (s, 3H), 1.14 (s, 3H), 1.05 (s, 3H); 13C NMR (75 MHz, CDCl3):
4.1.56. 62:
2a,7-dimethyl-1a,2,2a,3,4,5,7,7a-octahydronaphtho[2,3-b]oxiren-3-yl
benzoate. 1H NMR (300 MHz, CDCl3):
(1aS,2aR,3S,5R,7S,7aR)-5-(1-Hydroxy-1-methylethyl)-
d 165.9, 142.8, 132.9, 130.3, 129.5 (2C), 128.4 (2C), 121.4, 107.9, 78.8,
76.7, 73.1, 72.2, 42.8, 38.9, 38.2, 34.7, 27.8, 27.6, 26.3, 26.2, 25.1, 22.7,
15.3; HRMS (ES): m/z calcd for C25H34O5Na (MþþNa): 437.2304;
found: 437.2320.
d
8.05 (d, J¼7.8 Hz, 2H), 7.59
(t, J¼7.8 Hz, 1H), 7.48 (t, J¼7.8 Hz, 2H), 5.62 (s, 1H), 5.10 (dd, J¼12.0,
3.6 Hz, 1H), 3.31 (t, J¼4.5 Hz, 1H), 3.08 (d, J¼3.6 Hz, 1H), 2.92 (q,
J¼7.8 Hz, 1H), 2.34 (dd, J¼11.1, 4.8 Hz, 1H), 2.16e2.01 (m, 2H),
1.97e1.88 (m, 1H), 1.53e1.41 (m, 1H), 1.34 (d, J¼7.8 Hz, 3H), 1.22 (s,
4.1.60. (1aS,2R,4S,4aS,5aS,8aR,9R,9aR)-2-(1-Hydroxy-1-
methylethyl)-4a,7,7,9-tetramethylperhydrooxireno[20,30:4a,5]naph-
tho[2,3-d][1,3]dioxol-4-yl benzoate (ꢀ)-66. To a DCM (2 mL) solu-
tion of (þ)-65 (25 mg, 0.06 mmol) were added mCPBA (20 mg,
0.08 mmol), NaHCO3 (7 mg, 0.08 mmol) at 0 ꢁC and allowed to stir
for 1.5 h. The reaction was quenched and followed by usual workup.
The concentrated crude material was loaded on a silica gel column
(30% EtOAc/hexane) to furnish 23 mg of (ꢀ)-66 (90%) as a colorless
3H), 1.19 (s, 3H), 1.16 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 166.2,
142.5,133.0, 130.4,129.5 (2C),128.4 (2C),125.6, 78.5, 72.3, 57.9, 51.4,
45.9, 38.7, 37.4, 33.6, 27.9, 26.5, 25.9, 25.8, 19.9.
4.1.57. (1S,2R,6S,7S,9R,12S)-12-Hydroxy-2,6,10,10-tetramethyl-11-
oxatricyclo [7.2.1.01,6]dodec-3-en-7-yl benzoate (ꢀ)-63. To a stirred
ice-cooled DCM solution of the epoxide 61 (10 mg, 0.03 mmol) was
added BF3$OEt2 (0.01 mL, 0.09 mmol). After stirring at 0 ꢁC for 1 h,
the reaction was quenched with water and diluted with DCM
(10 mL). The organic extract was washed with water (2 mL), bi-
carbonate solution (2 mL), and brine then dried over anhydrous
Na2SO4. The crude material was purified through silica gel column
chromatography (20% EtOAc/hexane) to afford 9 mg of (ꢀ)-63
liquid; [
NMR (300 MHz, CDCl3):
a
]
23 ꢀ19.0 (c 1.0, CHCl3); IR (neat): nmax 3452, 1718 cmꢀ1; 1H
D
d
8.02 (d, J¼7.8 Hz, 2H), 7.57 (t, J¼7.8 Hz,
1H), 7.45 (t, J¼7.8 Hz, 2H), 4.96 (dd, J¼11.7, 3.6 Hz, 1H), 4.51e4.43
(m, 1H), 4.18e4.16 (m, 1H), 3.13 (s, 1H), 2.19e1.92 (m, 4H), 1.77e1.73
(m, 2H), 1.52 (s, 3H), 1.37 (s, 3H), 1.31 (s, 3H), 1.30 (s, 3H), 1.22 (d,
J¼7.8 Hz, 3H), 1.15 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 165.9, 133.1,
130.2, 129.6 (2C), 128.4 (2C), 108.0, 79.5, 75.9, 72.1, 71.3, 65.4, 64.2,
44.8, 38.8, 37.6, 32.3, 28.5 (2C), 26.2, 26.1, 24.0, 19.8, 16.0; HRMS
(92%); [
NMR (300 MHz, CDCl3):
a
]
22 ꢀ70.0 (c 0.3, CHCl3); IR (neat): nmax 3394, 1710 cmꢀ1; 1H
D
d
8.08 (d, J¼7.8 Hz, 2H), 7.56 (t, J¼7.8 Hz,
(ES): m/z calcd for
453.2291.
C
25H34O6Na (MþþNa): 453.2253; found:
1H), 7.44 (t, J¼7.8 Hz, 2H), 5.65e5.60 (m, 1H), 5.56e5.51 (m, 1H),
5.29 (d, J¼9.0 Hz, 1H), 4.73 (s, 1H), 2.92 (br s, eOH), 2.88e2.78 (m,
2H), 2.32 (m, 1H), 2.08e2.04 (m, 1H), 1.98e1.96 (m, 1H), 1.65 (d,
J¼3.3 Hz, 1H), 1.54 (s, 3H), 1.44 (s, 3H), 1.33 (s, 3H), 1.32 (d, J¼8.1 Hz,
4.1.61. (1S,2R,3R,4S,6S,7S,9R,12S)-3,4,12-Trihydroxy-2,6,10,10-
tetramethyl-11-oxatricyclo[7.2.1.01,6]dodec-7-yl benzoate (ꢀ)-67. To
a stirred DCM solution of the epoxide (ꢀ)-66 (18 mg, 0.04 mmol)
was added TMSOTf (0.02 mL, 0.10 mmol) at 0 ꢁC and the reaction
was stirred at the same temperature for 1 h. The reaction was
quenched with water and diluted with ethyl acetate (10 mL). The
organic extract was washed successively with water (2 mL), bi-
carbonate solution (2 mL), and brine then dried over anhydrous
Na2SO4. The crude material was charged on a silica gel column (75%
3H); 13C NMR (75 MHz, CDCl3):
d 166.2, 132.8, 130.6, 129.6 (3C),
128.4 (2C), 124.9, 81.9, 77.9, 76.1, 75.0, 47.1, 43.2, 43.0, 33.3, 30.8,
27.7, 25.6, 25.0, 16.1; HRMS (ES): m/z calcd for C22H28O4Na
(MþþNa): 379.1885; found: 379.1916.
4.1.58. (1S,3R,5S,6R,7S,8aR)-6,7-Dihydroxy-3-(1-hydroxy-1-
methylethyl)-5,8a-dimethyl-1,2,3,5,6,7,8,8a-octahydro-1-
naphthalenyl benzoate (þ)-64. To a solution of (ꢀ)-59 (50 mg,
0.15 mmol) in 3 mL of acetone/water (4:1) was added catalytic
amount of the OsO4 and NMO (26 mg, 0.23 mmol) and allowed to
stir at room temperature for 3 h. The reaction was quenched with
saturated solution of the sodium sulfite and filtered through a Cel-
ite pad. The concentrated residue was loaded on a silica gel column
EtOAc/hexane) to deliver 9 mg of (ꢀ)-67 (55%) as a colorless solid;
22
mp: 213e214 ꢁC; [
a]
ꢀ11.1 (c 0.5, CHCl3); IR: nmax 3438,
D
1711 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d
8.06 (d, J¼7.2 Hz, 2H), 7.58
(t, J¼7.5 Hz,1H), 7.47 (t, J¼7.5 Hz, 2H), 5.09 (d, J¼7.5 Hz,1H), 4.70 (br
s, 1H), 4.30 (d, J¼9.9 Hz, 1H), 3.91 (br s, eOH), 3.69 (d, J¼9.6 Hz, 1H),
2.72e2.70 (m,1H), 2.46e2.43 (m,1H), 2.36e2.20 (m, 2H), 2.05e1.93
(m, 2H), 1.79 (br s, eOH), 1.62 (br s, eOH), 1.48 (s, 6H), 1.32 (s, 3H),
(80% EtOAc/hexane) to furnish 52 mg of triol (þ)-64 (95%) as a liq-
23
uid; [
a
]
þ52.1 (c 1.7, CHCl3); IR (neat): nmax 3393, 1715 cmꢀ1
;
1H
1.31 (d, J¼7.8 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 166.1, 132.9,
D
NMR (300 MHz, CDCl3):
d
7.97 (d, J¼7.2 Hz, 2H), 7.55 (t, J¼7.2 Hz,
130.4, 129.6 (2C), 128.5 (2C), 83.4, 79.7, 76.9, 76.0, 75.8, 65.9, 47.8,
1H), 7.41 (t, J¼7.2 Hz, 2H), 5.62 (s, 1H), 5.03 (dd, J¼11.4, 3.6 Hz, 1H),
4.17e4.10 (m, 1H), 3.86 (s, 1H), 3.10 (br s, eOH), 2.66 (q, J¼2.4 Hz,
1H), 2.31 (dd, J¼10.2, 5.1 Hz, 1H), 1.98e1.83 (m, 3H), 1.75e1.71 (m,
1H), 1.31 (s, 3H), 1.25 (d, J¼7.8 Hz, 3H), 1.22 (s, 6H); 13C NMR
46.9, 45.4, 35.8, 30.5, 25.4, 25.3, 25.1, 14.9; HRMS (ES): m/z calcd for
C
22H30O6Na (MþþNa): 413.1940; found: 413.1945.
4.1.62. Crystallographic information of (ꢀ)-67. The compound was
crystallized from MeOH solvent system. Mf¼C22H30O6, MW¼390.48,
(75 MHz, CDCl3):
d 166.2, 142.2, 133.0, 130.2, 129.5 (2C), 128.4 (2C),
126.5, 79.1, 75.4, 72.0, 66.4, 47.2, 44.8, 39.9, 35.5, 28.2, 27.2, 25.4,
25.3, 19.2; HRMS (ES): m/z calcd for C22H30O5Na (MþþNa):
397.1991; found: 397.2012.
Crystal system: monoclinic, space group: P2(1), cell parameters:
ꢀ
a¼8.198 (2), b¼15.354 (4), c¼16.138 (4) A,
b
¼94.364 (5),
3
ꢀ
V¼2025.55 A , Z¼4, rcalcd¼1.28
g
cmꢀ3
,
F(000)¼840.0,
m
¼0.09 mmꢀ1. Total number of l.s. Parameters¼239, R1¼0.0897 for
4.1.59. (3aS,4aR,5S,7R,9S,9aR)-7-(1-Hydroxy-1-methylethyl)-
2,2,4a,9-tetramethyl-3a,4,4a,5,6,7,9,9a-octahydronaphtho[2,3-d][1,3]
dioxol-5-yl benzoate (þ)-65. To a stirred solution of (þ)-64 (40 mg,
0.11 mmol) in dry acetone (2 mL) were added Amberlyst-15 resin
5614 Fo>4
s
(Fo) and 0.1226 for all 7976 data. wR2¼0.2182,
GOF¼1.025, Restrained GOF¼1.025 for all data (CCDC number is
214305).
ꢀ
and 4 A mol. sieves at room temperature. After 4 h, the reaction was
Acknowledgements
filtered through a Celite pad. The filtrate was concentrated under
reduced pressure and directly charged on a silica gel column (20%
EtOAc/hexane) to deliver 36 mg of acetonide derivative (þ)-65
This research was carried out at IISc Bangalore and partly sup-
ported by the chemical biology unit of JNC, Bangalore. One of us
(R.S.K.) thanks Council of Scientific and Industrial Research (CSIR)
and IISc for research fellowship. G.M. thanks CSIR for the award of
Bhatnagar Fellowship and research support.
(81%); [
a
]
23 þ35.9 (c 1.7, CHCl3); IR (neat): nmax 3437, 1714 cmꢀ1; 1H
D
NMR (300 MHz, CDCl3):
d
7.94 (d, J¼7.2 Hz, 2H), 7.54 (t, J¼7.2 Hz,
1H), 7.42 (d, J¼7.2 Hz, 2H), 5.79 (s, 1H), 5.16 (t, J¼4.2 Hz, 1H), 4.54

R. Senthil Kumaran, G. Mehta / Tetrahedron 71 (2015) 1718e1731
1731
M.; Zhou, L.-G.; Yu, Z.-X. Org. Lett. 2010, 12, 2528e2531; (e) Siwicka, A.; Cuperly,
D.; Tadeschi, L.; Vezouet, R. L.; White, A. J. P.; Barrett, A. G. M. Tetrahedron 2007,
63, 5903e5917; (f) Heliwell, M.; Thomas, E. J.; Whitehouse, D. L. Synthesis 2005,
19, 3235e3238; (g) Lee, C. A.; Floreancig, P. E. Tetrahedron Lett. 2004, 45,
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