A Base-Catalyzed, Domino Aldol/hetero-Diels-Alder Synthesis of Tricyclic Pyrano[3,4-c]chromenes in Glycerol

Article abstract of DOI:10.1021/acs.joc.6b00107

The domino aldol/hetero-Diels-Alder synthesis of some new tricyclic pyrano[3,4-c]chromene derivatives has been achieved successfully after assembling a variety of acyclic or cyclic monoketones with prenyl ether-tethered aldehydes in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene in glycerol at 120 °C. The hitherto unreported stereochemical outcome of this synthetic sequence was studied and established on the basis of single-crystal X-ray diffraction data and 2D NMR NOESY spectroscopy along with the isolation and characterization of the intermediate Aldol condensation product.

Full text of DOI:10.1021/acs.joc.6b00107

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Article
A Base-Catalyzed, Domino Aldol/hetero-Diels-Alder
Synthesis of Tricyclic Pyrano[3,4-c]chromenes in Glycerol
Bhagyashri Dipakbhai Parmar, Tushar Ravjibhai Sutariya, Gaurangkumar
C. Brahmbhatt, Narsidas Jeramdas Parmar, Rajni Kant, and Vivek K Gupta
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00107 • Publication Date (Web): 12 May 2016
Downloaded from http://pubs.acs.org on May 13, 2016
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A Base−Catalyzed,DominoAldol/heteroꢀDielsꢀAlder Synthesis of
Tricyclic Pyrano[3,4ꢀc]chromenes in Glycerol
Bhagyashri D. Parmar,† Tushar R. Sutariya,†Gaurangkumar C. Brahmbhatt,†Narsidas J. Parmar,∗,†
Rajni Kant‡ and Vivek K. Gupta‡
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†
Department of Chemistry, Sardar Patel University, Vallabh Vidyanagar 388120, Dist. Anand, Gujarat, India
eꢀmail: njpchemdeptspu@yahoo.co.in
‡
PostꢀGraduate Department of Physics, University of Jammu, Jammu Tawi 180006, India
Abstract
The dominoAldolꢀheteroꢀDielsꢀAlder (DAHDA) synthesis of some new tricyclic pyrano[3,4ꢀ
c]chromene derivatives has been achieved, successfully after assembling a variety of acyclic or
cyclic monoketoneswith prenylꢀetherꢀtethered aldehydes in the presence of 1,8ꢀ
diazabicyclo[5.4.0]undecꢀ7ꢀene (DBU)in glycerol at 120 ℃. Hitherto unreported stereoꢀchemical
outcome of this synthetic sequence was studied and established on the basis of the singleꢀcrystal Xꢀ
ray diffraction data and 2D NMR NOESY spectroscopy,along with the isolation and
characterization of the intermediate, Aldolcondensation product.
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Introduction
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The pyranochromene has gained much prominence worldwide because of its existence as a
principal structural, central skeletonin several bioactive natural and unnatural molecular
frameworks, as well as in many photosensitive molecular assemblies.1 Due to a wide spectrum of
biological features of these frameworks such as antiꢀhyperglycemic and antiꢀoxidant properties,
and antiꢀdyslipidemic, antiꢀfungal, antiꢀmalarial, antiꢀcancer, antiꢀinflammatory, antiꢀtuberculosis,
antiꢀHIV, antialergic, antiviral, cytotoxic and antiꢀbacterial activities,2 class of these candidates has
attracted a wider scope of its utilizations and studies in the development of medicinal chemistry as
potential therapeutic agents. They are cognitive enhancers effective in the treatment of several
neurodegenerative diseases including Alzheimer’s diseases, AIDSꢀassociated dementia,
Schizophrenia, amyotrophic lateral Sclerosis, Huntington’s diseases and Parkinson’s
diseases.3Further, the pyranopyranyl core structure is known for conferring a variety of properties
on pyranochromeneꢀring systems through its varied patterns of the fusionexisting in thistricyclic
system in the molecules.4 Pyrano[3,2ꢀc]chromene, especially, finds an increasing applicationsin the
development of photonic materials, emerging as a promising photochrometic molecular motif with
great technological imortance.5
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Occurrence of pyranoꢀchromenenucleus could be recognized possibly in number of ways,
as shown in Figure 1, which ultimately results into several structural arrays or scaffolds which are
existing between pyran and chromene units, and each can be disguised by a relative position of two
oxygen atoms in pyranopyranyl skeleton.6Among these skeletons, pyrano[3,4ꢀc]chromeneunit
exists in number of potentially antiꢀproliferative,polyphenolic compoundsavailable naturally from
the plants Alpinia blepherocalyx.7 Recently, a great deal of interest in the chemistry of these
privileged biomolecules of this family; say Calyxin I and itsrelated compounds, has been seenin the
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literature, in both the partial and total syntheses of analogous systems and compounds8which
contains pyranoꢀfused pyran framework. To date,a very fewreports have been appeared onCalyxin
and Calyxinꢀanalogous scaffolds,relative to other pyranoꢀchromene systemswhich belongs to a
class of compounds with a pyrano[3,4ꢀc]chromene fusion. Li and coꢀworkers have reported stereoꢀ
selective synthesis ofracemicpyranochromenesA (R = Ph, R’ = H), using Prins−Friedel−Crafts
reaction. On the other hand, a stepwise synthetic protocolfor analogous systems (R = R’ =pꢀMeꢀ
phenyl) was given by Mead and coꢀworkers. Willis and coꢀworkersreported a singleꢀpot synthesis
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of
pyranochromenes
B
(R
=
Aryl,
Ethyl)
using
trimethylsilyl
trifluoromethanesulfonate.9Construction of this system by developingthe efficient synthetic
methodology is therefore desirable and worth interesting area of synthetic organic chemistry, in
support of the drug discovery program, with many new bioactive scaffolds.
A highly atom economic, efficientand yet environmentally friendly method has been the
prime synthetic target to be achieved by the chemists for synthesizing complex heterocycles,since
last few decades.10 Domino strategies11in this context seem to have widely explored by coupling
Knoevenagel transformation with heteroꢀDielsꢀAlder,12 ene,13allylsilane cyclization14 and 1,3ꢀ
dipolar cycloaddition15 reactions, in the development of cascade synthetic routes for synthesis of
diverse range of bioactive fusedꢀring systems.In the same way, imine16 generation coupled with
heteroꢀDielsꢀAlder transformation happened to be interesting example of growing research areas of
the synthetic organic chemistry. Hydroxylation–oxidation−DielsꢀAlder,17 Sakurai Carbonyl−ene,18
PictetꢀSpengler−ene,19 Alkyl radical addition−Aldol,20 Michael−Aldol21 and Claisenꢀ
Schmidt−Michael22 reactions are other domino routes appeared in the literature. To the best of our
knowledge, Aldolcondensation coupled to the heteroꢀDielsꢀAlder reactionremained a very rarely
employed synthetic sequenceinvolving use of mono ketone unit, relative to domino Knoevenagelꢀ
heteroꢀDielsꢀAlder sequence which utilized diketone units.23Further, thisprotocol in general
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remained applicable to cyclic ketoneswhich are revealing methylene hydrogen activation through
CꢀO carbon linked methylene carbon.As poor enolizable CH activated compounds (pKa =
19)24,mono ketones, i.e. acetophenone, are prone to show less reactivity towards aldehyde, relative
to 1,3ꢀdiketone units, and which might have kept this area unattended. Notably, assemblies of
cyclic and heterocyclic diketones with aldehyde substrates including our recently studied typical
combination; diketone witholefin tethered ketone,25have been widely reported in the
literature,employing domino KnoevenagelꢀheteroꢀDielsꢀAlder reaction. In present work, we
demonstrate domino AldolꢀheteroꢀDielsꢀAlder reaction in the presence of catalyst DBU in glycerol,
used efficiently for the synthesis of new pyrano[3,4ꢀc]chromenes which are analogous to the core
tricyclicframeworks of Calyxins.
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Figure 1.Tetrahydropyranochromene framework from Alpiniablepherocalyx and reported synthetic
fragments
Use of glycerol in the development of new and innovative processes26has been realized
greatly in the past few years, as it is associated with many advantages over conventional volatile
organic solventswhich are associated with the generation of hazardous wastes.Produced at the end
of hydrolysis and transꢀesterification of fats,glycerol is an alternative feed source with neverꢀending
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resources.As a nonꢀflammable and biodegradable material, it fulfilsalmost all the green chemistry
principles of being used as a solvent.27Preferable over water, especially when hydrophobic
substrates are employed,this medium with polar and nonꢀpolar nature allowed dissolution of
number of inorganic salts, acids, bases, enzymes, transition metal complexes and even waterꢀ
immiscible organic compounds. Not only this, it also helpedthe reaction products to single out
simply by liquid–liquid phase extraction, due to its immiscible nature with hydrophobic ethers and
hydrocarbons.Moreover, pharmaceutically active ingredients could be synthesizedin glycerol,where
alittle care is required to handle and storagethem due to nonꢀtoxicnature of this medium, in addition
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to its high boiling point (290 C). In present work, we therefore interested in developing the
DAHDA synthetic sequence using glycerol as an effective reaction medium, taking into account
above advantages. Transformations such as Pdꢀcatalyzed Heck reactions,28 Suzuki28a crossꢀ
coupling transformations by Perin29 and others,28,30 base28b and acid29a promoted condensations,
asymmetric reduction28c, catalytic hydrogenation,28c,30a multicomponent reactions,31 and
DKHDA,25g reported by us, have successfully been optimized in this medium.
Results and Discussion
Prenylation
of
salicylaldehyde2and
2ꢀhydroxyꢀnaphthaldehyde
3
gave
Oꢀ
prenylatedsalicylaldehydes4aand naphthaldehydes4b,as requisite aldehyde substrates,in higher
yields; 95% and 96% (Isolated) respectively, with prenyl bromide 1,stirred in the suspension of
anhydrous K2CO3 in DMF (dimethyl formamide) solution at room temperature (Scheme 1).
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Scheme 1. Reagents and conditions: (i) DMF, K2CO3, RT, 8ꢀ10 h
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Table 1.Reaction Condition Optimizationa
Catalyst
(25 mol %)
50 % KOH
Piperidine
Piperidine
DBU
DBU
K2CO3
DBU
Piperidine
TEA
LꢀProline
DBU
DBU
DBU (10)
DBU (15)
T
(ºC)
Time
(h)b
72
18
15
12
24
48
7
Yield
(%)c
70
70
ꢀd
Entry
Solvent
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2
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5
6
7
8
9
10
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12
13
14
Water
Water
Ethanol
Water
Toluene
Reflux
Reflux
Reflux
Reflux
Reflux
120
75
ꢀ
N,NꢀDimethyl formamide
Ethylene Glycol
Glycerol
15
65
78
ꢀd
120
120
7
Glycerol
120
20
20
4
7
7
Glycerol
120
ꢀd
Glycerol
120
89
80
65
76
Glycerol
100
Glycerol
120
Glycerol
120
6
aReaction conditions: 4b(0.2 mmol), 5a (0.2 mmol) and base in solvent (15 mL) stirredat the
b
c
d
specified temperature. Determined by TLC. Isolatedyields. Aldol intermediate.DBU = 1,8ꢀ
Diazabicyclo[5.4.0]undecꢀ7ꢀene. TEA = Triethylamine.
A combination between 2ꢀprenyloxyꢀnaphthaldehyde 4b and acetophenone5a was taken as
a model reaction to study and optimize the reaction conditions (Table 1). The reaction was first
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examined in the presence of 50% KOH in water at reflux. It yielded 70% of the desired products
but after prolong (72 h) stirring(entry 1). We then examined 25 mol% of piperidine in water at
reflux.The reaction time was improved;but it failed to improve the yield (entry 2). Trying
ethanolreplacing water as another protic solventat refluxfavoured only Aldol intermediate
generation (entry 3). Aldolintermediateis stable and can be isolated. Thus, all these results led to
the assumption that hydrogen bonds might be playing role to influence the reaction more
favourably in the water rather than in ethanol,and so water was continued as a solvent in the next
optimization testing (entry 4). Both the yield and reaction time were improved in the presence of
basic catalyst DBU in refluxing water(entry 4). The performance of catalyst DBU was very poor in
toluene, which may be attributed to its aprotic nature (entry 5). Anhydrous K2CO3 in DMFwas then
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tried at 120 C, to bring further improvement in the reaction (entry 6).Unfortunately, a very poor
yield of desired product (15 %) wasseen after long reaction time, i.e. 48 h. Despite the reaction time
can be shortened in the presence of DBU in ethylene glycol,where it gave 65% yields (entry
7),association of undesirable impurities with the products didn’t encourage its further testing. These
issueswere held no longer in the presence of piperidine in glycerol (entry 8). Other bases such as
TEA (entry 9) and Lꢀproline (entry 10) were failed to promote this protocol, though favoured the
formation of Aldol intermediate efficiently. Finally, the combination of catalyst DBU and solvent
glycerol worked effectively at 120 oC, giving excellent yields of DAHDA product 7baafter 4 h.The
product yield was however affected by decreasing the temperature and DBU amount in glycerol
(entries 12, 13, and 14). This observation was therefore considered better in favour of effective
electrophilic activation of the aldehyde, relative to that in the water.32Effective25 mol% load of
o
DBU in glycerol at 120 C(entry 11) was used to synthesize other heterocycles;7aaꢀ7af and 7baꢀ
7bf (Scheme 2). The reaction was monitored periodically for its progress by the TLC. The reaction
mass was poured into water, after completion of the reaction. Viscid matter thus came out of the
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aqueous mixture was extracted thrice with 20 mL portion of ethyl acetate. Combined extracts were
then dried over anhydrous Na2SO4, and evaporated to dry. The solid residue obtained was purified
finally by column chromatography on silica gel using a hexaneethyl acetate (9:1, v/v) mixture as an
eluent. The proposed structure of the product tetrahydropyrano[3,4ꢀc]chromene,7ba, was
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unambiguously confirmed by the singleꢀcrystal Xꢀray diffraction data, supported well by IR, H
NMR and 13C NMR spectral data, too. Intermediates, 6aaꢀ6af, 6baꢀ6bf,for the corresponding
cyclised products;7aaꢀ7af, 7baꢀ7bf,were also isolated (Table 2), and characterizedas Aldol
condensation products.Structure of Aldol intermediate 6afwas further confirmed by the single
crystal Xꢀray diffraction data.
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Scheme 2.Synthesis of Aldol intermediates, 6aaꢀ6af and 6baꢀ6bf and their
correspondingpyrano[3,4ꢀc]chromene derivatives,7aaꢀ7af and 7baꢀ7bf. Reagent and condition:
DBU in Glycerol, 120 oC
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Table 2.Synthesized Aldol intermediates; 6aaꢀ6af, 6baꢀ6bf, andtheir corresponding DAHDA
products; 7aa–7af,7ba–7bf
6
7
8
9
Aldol
Intermediate
6aa
Time
(h)
Yield
(%)a
87
89
84
90
89
88
91
86
85
82
91
Time
(h)
Yield
(%)a
80
78
75
76
79
80
89
85
82
80
84
Entry
Product
Entry
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4.5
5.0
5.5
6.5
4.5
5.0
4.0
4.5
5.0
5.5
3.5
4.0
7aa
7ab
7ac
7ad
7ae
7af
7ba
7bb
7bc
7bd
7be
7bf
2.0
2.0
2.5
3.0
1.5
2.5
1.5
2.0
2.5
2.0
1.5
2.0
6ab
6ac
6ad
6ae
6af
6ba
6bb
6bc
10
11
12
6bd
6be
6bf
83
90
aIsolatedyield.
A mechanistic pathway of the reaction is shown in Scheme 3.Reaction proceeds with the
Aldolcondensation reaction initially, which is followed by the heteroꢀDielsꢀAlder reaction, leading
to the formation of cyclised products. The stereochemistry of the product is governed by the
orientation ofprenyl−dienophiletowards Aldol,oxaꢀbutadiene, alkene, favourable in the reaction.
Theoretically, four possible transition states namely exoꢀEꢀanti,endoꢀEꢀsyn,endoꢀZꢀantiand exoꢀZꢀ
syn33are anticipated to materialize from the exo and endo orientations of dienophile towards
AldolEꢀene and Zꢀene intermediates.Out of these, endoꢀZꢀantiand exoꢀZꢀsyn didn’t get chance to
appear in the present case, as all the isolated Aldol intermediates are identified with Eꢀgeometry,
confirmed by 1H NMR data. Here, J value of both of the Aldol alkene protonsis found in the 15.6ꢀ
18 Hz range, for their characteristic and respective signals; one at ꢀ 7.76ꢀ8.32 ppm and second at ꢀ
8.11ꢀ8.65 ppm, confirming Eꢀgeometry of the intermediate. The singleꢀcrystal Xꢀray diffraction
data of representative 6af(Scheme3) confirmed the same unambiguously.Severe angle strain and
unfavourable steric interactions are other strong reasons to exclude the possibility of endoꢀZꢀ
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antistate.34 Thus, exoꢀEꢀantiandendoꢀEꢀsynare the only states that might be taking part in governing
4
5
6
1
the stereochemistry of the products. H NMR and nuclear Overhauser effect spectroscopy
7
8
9
(NOESY) data in combination with the single crystal Xꢀray diffraction study of representative
product 7ba,however, confirmed the cisꢀrelationship between pyranopyranlybridgeꢀhead protons;
Ha and Hb, ruling out the exoꢀEꢀantitransition;a state that leads to transꢀfused cyclized product
formation. 1,3ꢀAllylic strain35due to sp2ꢀgeminal effect rules out the possibility of exoꢀEꢀanti state,
further. The reaction was therefore concluded to be occurred through the most favoured endoꢀEꢀ
syntransition state36out of four possible transition states, leading to the formation of cisꢀproducts, in
all cases.Here, Aldol oxabutadiene and tethered olefin could be seen interacting well with each
other (Scheme 3).
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Scheme 3.The proposed reaction mechanism
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A doublet appeared at ꢀ 3.58ꢀ4.58 ppm, with J value in the 3.2ꢀ5.6 Hz range, can be
assigned to a pyranopyranyl bridgeꢀhead proton Ha, oriented cis to another bridgeꢀhead protonHb
which appeared as multiplate at ꢀ 1.90ꢀ2.31 ppm. Pyran alkene CH proton showed a singlet at ꢀ
5.37ꢀ5.74 ppm range, in all heterocycles except 7aeꢀ7af and 7beꢀ7bf. There is no alkene CH proton
in 7aeꢀ7af, and 7beꢀ7bf,due to participationof this proton in the fusion. While protons of methyl
atteched to the pyran ring showed a singlet at ꢀ 1.28ꢀ1.84 ppm, pyranyl ꢀOCH2 protons were
appeared multiplet in the ꢀ 3.61ꢀ4.62 ppm range, in all compounds. Increased in coupling constant
J values of the methylene protons exceptionally to a larger magnitude (~22), can be attributed to a
rigid disposition of these protons with respect to adjucent π system, in compounds 7af and 7bf
derived from the monoketone indanone.37
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The compound 7ba crystallises in the monoclinic space group P21/cwith the following unitꢀ
cell parameters: a = 11.7252(2), b = 12.2681(2), c = 12.3225(3) Å, β= 97.388(2)º, Z = 4. An
ORTEP view with atomic labelling is shown in Figure 2.
Figure 2.ORTEP view of the compound 7ba, with displacement ellipsoids drawn at the 40%
probability level.
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The recyclability of glycerol was tested at least three times,for the reaction, after it was
recovered from the reaction mass. The glycerol was recovered by using following treatments. The
reaction mass was first poured into water, allowing crude product to appear insoluble and hence
extractable with the ethyl acetate. The glycerolꢀwater mixture thus left was heated at 100 o C under
reduced to remove water. This recovered glycerol was then reused for the reaction.
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Conclusions
In summary,we demonstrated the synthesis of many new tricyclic pyrano[3,4ꢀc]chromeneꢀ
derivatives viaa domino AldolꢀheteroꢀDielsꢀAlder reactionin presence of catalyst DBU in glycerol,
studied very rarely. Use of enolizable CH activated acyclic monoketone in present work is
advantageous over DKHDA protocol, to construct the core structure which is analogues to the
tricyclic pyrano[3,4ꢀc]chromene framework present in Calyxins, which are known to exhibit strong
antiproliferative activity. DKHDA approach has been explored largely with cyclic or heterocyclic
diketone units,generating mostly teteracyclicpyranꢀframework with the aldehyde substrate,
compared to the present protocol. Glycerol employed in the present work worked not only as
efficient reaction medium, but as recyclable medium too, which can be recycled simply for its reꢀ
use, at least three times, in the same synthetic sequence without losing its activity.
EXPERIMENTAL SECTION
General Considerations:All commercially available reagents including solvents were used
13
without purification.Recorded all melting points are uncorrected.1H NMR and C NMR spectra
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13
were recorded at 400 MHz for H NMR and 100 MHz for C NMR as solutions in CDCl3, unless
and otherwise indicated. Chemical shiftvaluesare expressed in parts per million (ppm, δ) and
referenced to the residual protic solvent. Coupling constants are expressed in Hertz (Hz). Splitting
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patterns are designated as s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet. The degree of
substitution (C, CH, CH2, and CH3) was determined by the APT method.Elemental analysis was
carried out with an elemental analyser.The ESI mass spectra were measured on mass
spectrometer.TLC was performed on preꢀcoated silica plates, and spots were detected either by
means of UV (254 nm, 366 nm) or permanganate solution [KMnO4 (3 g), K2CO3 (20 g), NaOH (5
mL, 5% in H2O), H2O (300 mL)] or 2,4 dinitro phenyl hydrazine solution [2,4ꢀDNP (12 g), Conc.
H2SO4 (6 mL), Water (8 mL), EtOH (20 mL)].
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General procedure for synthesis of Oꢀprenylated aldehydes (4a and4b):To a stirred solution of
2 or 3 (10 mmol; 1.22 g of 2, 1.72 g of 3), suspended in anhydrous potassium carbonate (15 mmol;
2.07 g) in DMF (25 mL), was added dropꢀwise a solution of prenyl bromide 1 (13 mmol; 1.94 g)
prepared in DMF (5 mL). The mixture was stirred further at room temperature until the reaction
was complete, confirmed by the TLC (10−12 h). The reaction mass gave products 4a/4b, when
poured into 100 g of ice with constant stirring. The oily product, 4a was extracted with three 25 ml
diethyl ether portions. The combined ether extracts were dried using anhydrous sodium sulphate
and evaporated to remove ether to have aldehyde, 4a.The yield of 4a was 95% andbp,
203―206℃.The solid product, 4b was filtered, washed with three 10 ml cold water portions
followed by room temperature drying. The yield of 4b was 96% and mp, 58ꢀ60 ℃.
General experimental procedure for the synthesis of Aldol intermediates (6aaꢀ6af and6baꢀ
6bf),and the cyclised products, pyrano[3,4ꢀc]chromenes(7aaꢀ7af and 7baꢀ7bf):A mixture of
acetophenone (0.240 g of 5a) or 1ꢀacetoꢀnaphthone (0.340 g of 5b) or 3ꢀacetyl pyridine (0.242 g of
5c) or 2ꢀacetyl fluorene (0.416 g of 5d) or 1ꢀtetralone (0.292 g of 5e) or 1ꢀindanone (0.264 g of 5f)
andOꢀprenylated salicylaldehyde (0.380 g of 4a) or Oꢀprenylated naphthaldehyde (0.480 g of 4b),in
equimolar amounts (2 mmol) was taken in glycerol (15 ml) in a roundꢀbottom flask,and added
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catalytic amount of DBU (25 mol %). The resulted reaction mass was then heated at 120 °C,
continuouly monitoring the formation of Aldol intermediate by TLC. Heating was stopped after
confirming the formation of Aldol intermediate by TLC (6aaꢀ6af and 6baꢀ6bf).The reaction mass
was poured into water,and extracted the crude product thrice with ethyl acetate. The content of
combined ethyl acetate extracts was dried over anhydrous Na2SO4 and evaporated. The desired
product in the residue thus left was purified further by column chromatography on silica gel using
an ethyl acetateꢀnꢀhexane mixture of appropriate polarity as an eluent giving pure intermediate
product (6aaꢀ6af and 6baꢀ6bf). The glycerolꢀwater mixrure that was left after the extraction of the
crude product with ethyl acetate was heated at 100 0 C under reduced pessure to remove water.This
recovered glycerol was reꢀused again for the reation.
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In order to access all cyclised products, 7aaꢀ7af and7baꢀ7bf, the reaction was continued to carryout
further that convertedcorresponding Aldol intermediates into heteroꢀDielsꢀAlder products,
monitered by the TLC. The workꢀup and purificationinvolved here are similar to what had been
applied to the isolation of Aldol intermediates.All the Aldol intermediates andtheir correspnding
products were characterized on the basic of their mass, IR, 1H NMR, and 13C NMR spectral data.
2ꢀ((3ꢀmethylbutꢀ2ꢀenꢀ1ꢀyl)oxy)benzaldehyde (4a). Yellow oil, yield 95 % (1807.2 mg), bp = 203ꢀ
206˚C;δH(400 MHz; CDCl3) 1.75 (s, 3H), 1.80 (s, 3H), 4.63 (d, J = 6.8 Hz, 2H), 5.49 (m, 1H), 7.00
(m, 2H), 7.52 (m, 1H), 7.82 (m, 1H), 10.49 (s, 1H); δC(100 MHz; CDCl3) 18.3, 25.7, 65.5, 113.0,
119.0, 120.5, 125.2, 128.2, 135.8, 138.6, 161.4, 189.9; Anal Calcd for C12H14O2: C, 75.76; H, 7.42;
Found: C, 75.53; H, 7.71; m/z (ESI) 191.2[M+H]+.
2ꢀ((3ꢀmethylbutꢀ2ꢀenꢀ1ꢀyl)oxy)ꢀ1ꢀnaphthaldehyde (4b). Creamy white solid, yield 96 % (2306.9
mg), mp = 58ꢀ60˚C; δH(400 MHz; CDCl3) 1.80 (s, 3H), 1.83 (s, 3H), 4.79 (d, J = 6.4 Hz, 2H), 5.55
(t,J = 6.8 Hz, 1H), 7.28ꢀ8.06 (m, 5H), 9.30 (d,J = 8.8 Hz, 1H), 10.92 (m, 1H); δC(100 MHz; CDCl3)
18.3, 25.8, 65.6, 114.2, 117.3, 118.9, 124.7, 125.0, 128.1, 128.6, 129.8, 131.7, 137.3, 139.3, 163.7,
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192.5; Anal Calcd for C16H16O2: C, 79.97; H, 6.71; Found: C, 79.63; H, 6.95; m/z (ESI)
241.3[M+H]+.
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(E)ꢀ3ꢀ(2ꢀ((3ꢀmethylbutꢀ2ꢀenꢀ1ꢀyl)oxy)phenyl)ꢀ1ꢀphenylpropꢀ2ꢀenꢀ1ꢀone (6aa). Yellow solid,
yield 87 % (508.8 mg), mp = 60ꢀ62˚C; νmax/cmꢀ1 = 2927, 2828, 1679, 1600, 1488, 1455, 1360,
1290, 1268, 1230, 1199, 1161, 1120, 1092, 1051, 999, 976, 955, 909, 853, 753, 741, 687; δH(400
MHz; CDCl3) 1.79 (s, 3H), 1.86 (s, 3H), 4.63 (d, J = 6.8 Hz, 2H), 5.60 (tt, J = 6.4, J =1.2 Hz, 1H),
6.97ꢀ7.65 (m, 7H), 7.80 (d, J = 16 Hz, 1H), 8.04ꢀ8.06 (m, 2H), 8.12 (d, J = 15.6 Hz, 1H); δC(100
MHz; CDCl3) 18.3, 25.8, 65.3, 112.5, 119.5, 120.7, 123.0, 124.2, 128.5, 130.2, 131.6, 132.5, 138.5,
138.6, 140.9, 158.4, 191.0;Anal Calcd for C20H20O2: C, 82.16; H, 6.89; Found: C, 82.45; H, 6.60;
m/z (ESI) 293.1[M+H]+.
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(E)ꢀ3ꢀ(2ꢀ((3ꢀmethylbutꢀ2ꢀenꢀ1ꢀyl)oxy)phenyl)ꢀ1ꢀ(naphthalenꢀ1ꢀyl)propꢀ2ꢀenꢀ1ꢀone
(6ab).Yellow Liquid, yield 89 % (609.6 mg),νmax/cmꢀ1 = 2928, 2828, 1680, 1602, 1481, 1457,
1358, 1293, 1271, 1236, 1197, 1160, 1125, 1090, 1058, 994, 972, 950, 901, 850, 758, 746, 688;
δH(400 MHz; CDCl3) 1.70 (s, 3H), 1.78 (s, 3H), 4.55 (d, J = 6.8Hz, 2H), 5.47 (t, J = 6.4 Hz, 1H),
6.91ꢀ7.99 (m, 11H), 8.11 (d, J = 16.4Hz, 1H), 8.52 (d, 1H); δC(100 MHz; CDCl3) 18.6, 26.1, 65.4,
112.7, 119.5, 120.8, 124.0, 124.6, 126.0, 126.4, 127.3, 127.4, 127.5, 128.5, 129.5, 130.7, 131.6,
132.0, 134.1, 137.6, 138.2, 141.7, 158.0, 195.9;Anal Calcd for C24H22O2: C, 84.18; H, 6.48; Found:
C, 84.42; H, 6.25; m/z (ESI) 343.2[M+H]+.
(E)ꢀ3ꢀ(2ꢀ((3ꢀmethylbutꢀ2ꢀenꢀ1ꢀyl)oxy)phenyl)ꢀ1ꢀ(pyridinꢀ3ꢀyl)propꢀ2ꢀenꢀ1ꢀone (6ac). Yellow
solid, yield 84 % (492.9 mg), mp = 57ꢀ59˚C; νmax/cmꢀ1 = 2924, 2854, 1720, 1659, 1598, 1568,
1488, 1451, 1414, 1381, 1332, 1281, 1245, 1199, 1164, 1123, 1085, 1051, 996, 978, 860, 813, 750,
703; δH(400 MHz; CDCl3) 1.79 (s, 3H), 1.87 (s, 3H), 4.65 (d, J = 6.8 Hz, 2H), 5.59 (m, 1H), 6.98ꢀ
7.65 (m, 5H), 7.76 (d, J = 15.6 Hz, 1H), 8.13 (d, J = 15.6 Hz, 1H), 8.30 (m, 1H), 8.81 (m, 1H), 9.24
(d, 1H); δC(100 MHz; CDCl3) 18.8, 25.9, 65.3, 112.5, 119.3, 120.8, 122.4, 123.5, 123.8, 130.6,
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132.0, 133.9, 135.9, 138.8, 142.2, 149.9, 153.0, 158.5, 189.8;Anal Calcd for C19H19NO2: C, 77.79;
H, 6.53; N, 4.77; Found: C, 77.54; H, 6.81; N, 4.49; m/z (ESI) 294.1[M+H]+.
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(E)ꢀ1ꢀ(9Hꢀfluorenꢀ2ꢀyl)ꢀ3ꢀ(2ꢀ((3ꢀmethylbutꢀ2ꢀenꢀ1ꢀyl)oxy)phenyl)propꢀ2ꢀenꢀ1ꢀone
(6ad).Yellow solid, yield 90 % (684.9 mg), mp = 107ꢀ109˚C;νmax/cmꢀ1 = 2927, 2828, 1678, 1568,
1488, 1454, 1360, 1290, 1230, 1161, 1093, 1051, 999, 853, 754; δH(400 MHz; CDCl3) 1.81 (s, 3H),
1.88 (s, 3H), 4.01 (s, 2H), 4.65 (d, J = 6.4 HZ, 2H), 5.63 (s, 1H), 6.98ꢀ7.68 (m, 7H), 7.86 (d, J =
14.8 HZ, 1H), 7.88ꢀ8.14 (m, 3H), 8.16 (d, J = 16 HZ, 1H), 8.26 (s, 1H); δC(100 MHz; CDCl3) 18.3,
25.9, 36.9, 65.3, 112.5, 119.5, 119.7, 120.7, 120.8, 123.2, 124.4, 125.3, 127.1, 127.9, 130.1, 131.5,
137.1, 138.4, 140.5, 140.7, 143.4, 144.5, 146.0, 158.4, 190.7 (ArꢀC); Anal Calcd for C27H24O2: C,
85.23; H, 6.36; Found: C, 85.46; H, 6.59; m/z (ESI) 381.2[M+H]+.
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(E)ꢀ2ꢀ(2ꢀ((3ꢀmethylbutꢀ2ꢀenꢀ1ꢀyl)oxy)benzylidene)ꢀ3,4ꢀdihydronaphthalenꢀ1(2H)ꢀone
(6ae).Yellow Liquid, yield 89 % (566.8 mg),νmax/cmꢀ1 = 2926, 2827, 1675, 1603, 1481, 1451, 1367,
1295, 1272, 1235, 1194, 1160, 1122, 1091, 1056, 990, 971, 957, 906, 857, 750, 747, 682; δH(400
MHz; CDCl3) 1.76 (s, 3H), 1.80 (s, 3H), 2.95 (t, 2H), 3.08 (t, 2H), 4.60 (d, J = 6.4 Hz, 2H), 5.52 (t,
1H), 6.97ꢀ7.02 (m, 2H), 7.25ꢀ7.51 (m, 5H), 8.08 (s, 1H), 8.19 (m, 1H); δC(100 MHz; CDCl3) 18.3,
25.8, 27.7, 29.1, 65.5, 112.2, 119.9, 120.0, 125.3, 126.9, 128.1, 128.2, 130.1, 130.3, 133.1, 133.6,
135.3, 137.5, 143.5, 157.7, 188.0;Anal Calcd for C22H22O2: C, 82.99; H, 6.96; Found: C, 82.76; H,
7.29;m/z (ESI) 319.2[M+H]+.
(E)ꢀ2ꢀ(2ꢀ((3ꢀmethylbutꢀ2ꢀenꢀ1ꢀyl)oxy)benzylidene)ꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀone (6af). Yellow
solid, yield 88 % (535.7 mg), mp = 89ꢀ91˚C; νmax/cmꢀ1 = 2925, 2828, 1670, 1609, 1487, 1455,
1366, 1299, 1270, 1233, 1192, 1168, 1120, 1094, 1058, 995, 974, 959, 902, 851, 757, 740, 687;
δH(400 MHz; CDCl3) 1.78 (s, 3H), 1.82 (s, 3H), 4.01 (s, 2H), 4.63 (d, J = 6.4 Hz), 5.54 (tt, J = 6.4
Hz, 1.2 Hz), 6.96ꢀ7.06 (m, 2H), 7.34ꢀ7.71 (m, 5H), 7.92 (d, 1H), 8.19 (t, 1H); δC(100 MHz; CDCl3)
18.3, 25.8, 32.4, 65.5, 112.5, 119.7, 120.4, 124.3, 124.8, 126.1, 127.5, 129.0, 129.8, 131.0, 134.4,
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134.6, 137.8, 138.3, 149.8, 158.5, 194.4;Anal Calcd for C21H20O2: C, 82.86; H, 6.62; Found: C,
82.59; H, 6.86;m/z (ESI) 305.1[M+H]+.
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solid, yield 91 % (623.2 mg),mp= 113ꢀ115˚C; νmax/cmꢀ1 = 2960, 2908, 2857, 1653, 1623, 1598,
1586, 1559, 1501, 1455, 1438, 1377, 1353, 1283, 1267, 1180, 1153, 1110, 1091, 1017, 979, 911,
852, 811, 799, 777, 753, 712, 658;δH(400 MHz; CDCl3) 1.81 (s, 3H), 1.87 (s, 3H), 4.79 (d, J = 6.8
Hz, 2H), 5.68 (t, J = 6.4 Hz, 1H), 7.34ꢀ8.34 (m, 12H), 8.60 (d, J = 16 Hz, 1H); δC(100 MHz;
CDCl3) 18.3, 25.9, 66.1, 114.3, 117.5, 119.5, 123.3, 124.0, 126.8, 127.1, 127.5, 127.7, 128.5,
128.6, 128.7, 129.1, 131.8, 132.5, 133.4, 137.5, 138.8, 139.0, 156.9, 191.2;Anal Calcd for
C24H22O2: C, 84.18; H, 6.48; Found: C, 84.34; H, 6.25; m/z (ESI) 343.2[M+H]+.
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(E)ꢀ3ꢀ(2ꢀ((3ꢀmethylbutꢀ2ꢀenꢀ1ꢀyl)oxy)naphthalenꢀ1ꢀyl)ꢀ1ꢀ(naphthalenꢀ1ꢀyl)propꢀ2ꢀenꢀ1ꢀ
one(6bb). Yellow solid, yield 86 % (675.1 mg), mp = 98ꢀ100˚C; νmax/cmꢀ1 = 2962, 2901, 2854,
1649, 1619, 1593, 1580, 1555, 1508, 1450, 1431, 1374, 1348, 1276, 1262, 1178, 1149, 1108, 1097,
1022, 977, 917, 856, 814, 795, 776, 745, 710, 655; δH(400 MHz; CDCl3) 1.75 (s, 3H), 1.78 (s, 3H),
4.76 (d, J = 6.4 Hz, 2H), 5.54 (tt, J = 6.8, J =1.2 Hz, 1H), 7.31ꢀ7.64 (m, 6H), 7.79 (d, J = 16 Hz,
1H), 7.83ꢀ8.20 (m, 6H), 8.41 (d, J = 16 Hz, 1H), 8.52 (d, 1H); δC(100 MHz; CDCl3) 18.3, 25.8,
66.2, 114.3, 117.3, 119.4, 123.3, 124.0, 124.6, 126.1, 126.4, 127.4, 127.5, 127.5, 128.4, 128.7,
129.0, 130.7, 131.6, 131.7, 132.0, 133.1, 133.9, 137.6, 138.6, 139.0, 156.7, 196.4;Anal Calcd for
C28H24O2: C, 85.68; H, 6.16; Found: C, 85.43; H, 6.42; m/z (ESI) 392.1[M]+.
(E)ꢀ3ꢀ(2ꢀ((3ꢀmethylbutꢀ2ꢀenꢀ1ꢀyl)oxy)naphthalenꢀ1ꢀyl)ꢀ1ꢀ(pyridinꢀ3ꢀyl)propꢀ2ꢀenꢀ1ꢀone (6bc).
Yellow solid, yield 85 % (583.8 mg), mp = 106ꢀ108˚C; νmax/cmꢀ1 = 3033, 2933, 1658, 1599, 1558,
1512, 1462, 1414, 1381, 1353, 1294, 1274, 1246, 1190, 1150, 1099, 1056, 1022, 1004, 972, 914,
851, 813, 790, 737, 710, 680; δH(400 MHz; CDCl3) 1.82 (s, 3H), 1.89 (s, 3H), 4.81 (d, J = 6.8 Hz,
2H), 5.67 (tt, J = 6.8, J =1.2 Hz, 1H), 7.35ꢀ7.93 (m, 6H), 8.10 (d, J = 15.6 Hz, 1H), 8.30ꢀ8.38 (m,
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2H), 8.65 (d, J = 15.6 Hz, 1H), 8.83 (s, 1H), 9.30 (s, 1H); δC(100 MHz; CDCl3) 18.3, 25.8, 66.0,
114.1, 116.8, 119.3, 123.1, 123.6, 124.1, 125.7, 127.7, 128.7, 129.0, 132.4, 133.5, 134.0, 135.9,
138.5, 139.5, 150.0, 152.9, 157.4, 189.8;Anal Calcd for C23H21NO2: C, 80.44; H, 6.16; N, 4.08;
Found: C, 80.72; H, 5.86; N, 4.28; m/z (ESI) 342.2[MꢀH]+.
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(E)ꢀ1ꢀ(9Hꢀfluorenꢀ2ꢀyl)ꢀ3ꢀ(2ꢀ((3ꢀmethylbutꢀ2ꢀenꢀ1ꢀyl)oxy)naphthalenꢀ1ꢀyl)propꢀ2ꢀenꢀ1ꢀone
(6bd). Yellow solid, yield 82 % (706.1 mg), mp = 101ꢀ103˚C; νmax/cmꢀ1 = 2965, 2907, 2850, 1656,
1623, 1598, 1576, 1551, 1502, 1446, 1435, 1370, 1350, 1279, 1264, 1180, 1153, 1113, 1099, 1028,
971, 910, 850, 811, 790, 769, 748, 715, 651; δH(400 MHz; CDCl3) 1.83 (s, 3H), 1.89 (s, 3H), 4.02
(s, 2H), 4.81 (d, J = 6.8 Hz, 2H), 5.70 (tt, J = 6.8, J =1.6 Hz, 1H), 7.36ꢀ8.18 (m, 13H), 8.32 (d, J =
18 Hz, 1H), 8.61 (d, J = 15.6 Hz, 1H); δC(100 MHz; CDCl3) 18.4, 26.1, 37.1, 66.4, 114.4, 119.6,
119.7, 120.9, 123.5, 124.0, 125.3, 125.4, 127.1, 127.2, 127.4, 127.9, 128.0, 128.6, 129.1, 131.7,
133.4, 137.2, 138.9, 140.7, 143.4, 144.5, 146.0, 156.8, 166.3, 190.9;Anal Calcd for C31H26O2: C,
86.48; H, 6.09; Found: C, 86.69; H, 6.33; m/z (ESI) 431.1[M+H]+.
(E)ꢀ2ꢀ((2ꢀ((3ꢀmethylbutꢀ2ꢀenꢀ1ꢀyl)oxy)naphthalenꢀ1ꢀyl)methylene)ꢀ3,4ꢀdihydronaphthaleneꢀ
1(2H)ꢀone (6be).Yellow solid, yield 91 % (670.6 mg),mp = 117ꢀ119˚C; νmax/cmꢀ1 = 2925, 2828,
1670, 1609, 1480, 1456, 1366, 1291, 1278, 1242, 1199, 1167, 1116, 1093, 1049, 991, 978, 951,
912, 848, 757, 754, 688; δH(400 MHz; CDCl3) 1.73 (s, 3H), 1.76 (s, 3H), 2.69 (t, 2H),2.92 (t, 2H),
4.68 (d, J = 6.4 Hz, 2H), 5.47 (t, J = 6.8 Hz, 1H), 7.25ꢀ7.54 (m, 6H), 7.80ꢀ7.89 (m, 3H), 8.13 (s,
1H), 8.25 (d, 1H); δC(100 MHz; CDCl3) 18.3, 25.7, 28.5, 29.1, 66.6, 115.3, 119.6, 120.1, 123.9,
124.7, 126.7, 126.9, 128.2, 128.3, 128.9, 130.0, 131.5, 132.7, 133.1, 133.7, 137.7, 138.6, 144.2,
154.0, 187.5;Anal Calcd for C26H24O2: C, 84.75; H, 6.57; Found: C, 84.95; H, 6.79; m/z (ESI)
369.2[M+H]+.
(E)ꢀ2ꢀ((2ꢀ((3ꢀmethylbutꢀ2ꢀenꢀ1ꢀyl)oxy)naphthalenꢀ1ꢀyl)methylene)ꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀ
one (6bf).Yellow solid, yield 90 % (638.0 mg),mp= 78ꢀ80˚C; νmax/cmꢀ1 = 2927, 2826, 1667, 1611,
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1485, 1451, 1360, 1297, 1283, 1244, 1200, 1161, 1111, 1097, 1053, 994, 970, 957, 915, 850, 751,
747, 680; δH(400 MHz; CDCl3) 1.73 (s, 3H), 1.75 (s, 3H), 3.64 (s, 2H), 4.70 (d, J = 6.8 Hz, 2H),
5.46 (m, 1H), 7.34ꢀ 7.61 (m, 6H), 7.84ꢀ7.97 (m, 4H), 8.15 (m, 1H); δC(100 MHz; CDCl3) 18.1,
25.8, 32.1, 66.8, 115.3, 116.3, 119.4, 119.9, 124.0, 124.4, 124.6, 126.1, 127.0, 127.4, 128.4, 129.0,
129.5, 130.5, 132.3, 134.5, 138.6, 139.9, 150.16, 153.4;Anal Calcd for C25H22O2: C, 84.72; H, 6.26;
Found: C, 84.51; H, 6.14; m/z (ESI) 355.2[M+H]+.
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4,4ꢀdimethylꢀ2ꢀphenylꢀ4,4a,5,10bꢀtetrahydropyrano[3,4ꢀc]chrcomene (7aa). White solid, yield
80 % (467.8 mg), mp = 142ꢀ144˚C; νmax/cmꢀ1 = 3062, 2960, 2926, 2873, 1800, 1714, 1680, 1602,
1583, 1533, 1490, 1452, 1380, 1230, 1177, 1117, 1024, 972, 755, 698; δH(400 MHz; CDCl3) 1.39
(s, 3H), 1.46 (s, 3H), 2.18 (m, 1H), 3.62 (t, J = 10.4 Hz, 1H), 3.71 (d, J = 5.6 Hz, 1H), 4.41 (d, J =
10.4 Hz, 1H), 5.43 (s, 1H), 6.79–7.54 (m, 9H); δC(100 MHz; CDCl3) 25.3, 26.1, 30.9, 37.0, 63.6,
75.2, 100.2, 116.6, 121.2, 124.8, 125.1, 127.3, 127.8, 128.5, 128.6, 130.5, 135.8, 146.9, 154.2;Anal
Calcd for C20H20O2: C, 82.16; H, 6.89; Found: C, 81.84; H, 7.12; m/z (ESI) 293.1[M + H+].
4,4ꢀdimethylꢀ2ꢀ(naphthalenꢀ1ꢀyl)ꢀ4,4a,5,10bꢀtetrahydropyrano[3,4ꢀc]chromene (7ab). White
solid, yield 78 % (534.2 mg), mp = 158ꢀ160˚C; νmax/cmꢀ1 = 3059, 2963, 2928, 2875, 1803, 1711,
1678, 1600, 1586, 1530, 1494, 1450, 1382, 1237, 1174, 1111, 1026, 968, 756, 695; δH(400 MHz;
CDCl3) 1.59 (s, 3H), 1.74 (s, 3H), 2.25 (m, 1H), 3.87(d, J = 5.6 Hz, 1H), 4.19 (m, 1H), 4.59 (m,
1H), 5.20 (s, 1H), 7.00ꢀ7.04 (m, 2H), 7.23ꢀ7.33 (m, 2H), 7.44ꢀ7.58 (m, 4H), 7.85ꢀ7.90 (m, 2H),
8.28 (d, 1H); δC(100 MHz; CDCl3) 25.7, 26.2, 29.8, 31.5, 38.4, 63.7, 104.1, 116.7, 121.0, 125.2,
125.6, 125.8, 126.2, 127.1, 127.7, 128.4, 129.0, 129.8, 131.5, 133.8, 134.7, 149.3, 154.3;Anal
Calcd for C24H22O2: C, 84.18; H, 6.48; Found: C, 84.44; H, 6.23;Anal Calcd for C24H22O2: C,
84.18; H, 6.48; Found: C, 84.44; H, 6.23; m/z (ESI) 343.2[M + H+].
3ꢀ(4,4ꢀdimethylꢀ4,4a,5,10bꢀtetrahydropyrano[3,4ꢀc]chromenꢀ2ꢀyl)pyridine (7ac). White solid,
yield 75 % (440.1 mg), mp = 134ꢀ136˚C;νmax/cmꢀ1 = 3060, 2957, 2925, 2874, 1804, 1712, 1683,
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1601, 1586, 1537, 1488, 1455, 1383, 1235, 1179, 1120, 1029, 977, 750, 692; δH(400 MHz; CDCl3)
1.39 (s, 3H), 1.46 (s, 3H), 2.06ꢀ2.12 (m, 1H), 3.66 (d, J = 6 Hz, 1H), 3.74 (t, J = 11.2 Hz, 1H), 4.33
(m, 1H), 5.33 (m, 1H), 6.77–8.71 (m, 8H);δC(100 MHz; CDCl3) 25.3, 26.0, 31.3, 37.5, 63.6, 75.2,
101.1, 114.1, 116.7, 120.9, 122.9, 124.1, 127.8, 129.6, 132.0, 145.3, 146.3, 148.9, 154.2; Anal
Calcd for C19H19NO2: C, 77.79; H, 6.53; N, 4.77; Found: C, 78.13; H, 6.90; N, 4.89; m/z (ESI)
294.1[M + H+].
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2ꢀ(9Hꢀfluorenꢀ2ꢀyl)ꢀ4,4ꢀdimethylꢀ4,4a,5,10bꢀtetrahydropyrano[3,4ꢀc]chromene (7ad). White
solid, yield 76 % (578.4 mg), mp = 160ꢀ162 ˚C;νmax/cmꢀ1 = 3063, 2950, 2928, 2878, 1810, 1708,
1688, 1600, 1589, 1540, 1482, 1457, 1381, 1239, 1182, 1122, 1033, 971, 756, 697; δH(400 MHz;
CDCl3) 1.41 (s, 3H), 1.48 (s, 3H), 2.08 (m, 1H),3.67 (d, J = 4.8 Hz, 1H), 3.80 (m, 3H), 4.34 (m,
1H), 5.31 (s, 1H), 6.77–7.70 (m, 11H); δC(100 MHz; CDCl3) 25.3, 26.2, 31.5, 36.9, 37.6, 63.8,
74.8, 99.4, 114.1, 116.7, 119.5, 119.9, 120.9, 121.4, 123.7, 124.7, 125.0, 126.7, 126.8, 127.6,
129.7, 141.4, 141.7, 143.2, 143.6, 147.8, 154.2; Anal Calcd for C27H24O2: C, 85.23; H, 6.36;
Found: C, 85.61; H, 6.73; m/z (ESI) 381.2[M + H+].
14,14ꢀdimethylꢀ1,6b,7,8,14,14aꢀhexahydronaphtho[3',4':5,6]pyrano[3,4ꢀc]chromene(7ae).
White solid, yield 79 % (503.2 mg), mp = 100ꢀ102˚C; νmax/cmꢀ1 = 3063, 3030, 1947, 1897, 1804,
1634, 1606, 1582, 1491, 1452, 1428, 1381, 1367, 1299, 1277, 1257, 1238, 1144, 1113, 1083, 1056,
1041, 862, 828, 767, 750, 737, 710; δH(400 MHz; CDCl3) 1.44 (s, 3H), 1.54 (s, 3H), 2.15 (m, 1H),
2.26 (m, 1H), 2.47 (m, 1H), 2.75 (m, 2H), 3.66 (d, J = 3.2 Hz, 1H), 4.05 (t, J = 11.2 Hz, 1H), 4.46
(dd, J = 10.8, J = 2 Hz, 1H), 6.86–7.55 (m, 8H); δC(100 MHz; CDCl3) 24.1, 25.7, 26.2, 28.1, 34.8,
37.8, 64.1, 73.8, 106.9, 116.6, 119.3, 121.4, 121.8, 126.2, 126.8, 127.2, 128.2, 132.0, 132.6, 136.0,
141.4, 154.4;Anal Calcd for C22H22O2: C, 82.99; H, 6.96; Found: C, 82.75; H, 7.19; m/z (ESI)
318.2[M]+.
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7,7ꢀdimethylꢀ6a,7,13,13bꢀtetrahydroꢀ6Hꢀindeno[2',1':5,6]pyrano[3,4ꢀc]chromene (7af).White
solid, yield 80 % (487.0 mg), mp = 166ꢀ168˚C; νmax/cmꢀ1 = 3060, 3034, 1950, 1899, 1800, 1637,
1608, 1580, 1495, 1450, 1427, 1380, 1368, 1292, 1275, 1255, 1231, 1148, 1112, 1086, 1055, 1040,
863, 829, 760, 756, 731, 711; δH(400 MHz; CDCl3) 1.47 (s, 3H), 1.61 (s, 3H), 2.23 (m, 1H), 3.09
(d, J= 21.6 Hz, 1H), 3.42 (d, J = 22 Hz, 1H), 3.89 (t, J = 11.2 Hz, 1H), 3.97 (d, J = 4.8 Hz, 1H),
4.45 (d, J = 10.4 Hz, 1H), 6.85–7.35 (m, 8H); δC(100 MHz; CDCl3) 25.6, 26.0, 32.8, 35.5, 38.6,
63.7, 76.5, 112.6, 116.7, 117.4, 120.3, 123.3, 123.7, 124.9, 126.2, 127.9, 130.8, 139.5, 141.8,
148.0, 154.2;Anal Calcd for C21H20O2: C, 82.86; H, 6.62; Found: C, 82.98; H, 6.76; m/z (ESI)
305.2[M + H+].
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4,4ꢀdimethylꢀ2ꢀphenylꢀ4,4a,5,12cꢀtetrahydrobenzo[f]pyrano[3,4ꢀc]chromene (7ba). White
solid, yield 89 % (609.6 mg), mp = 194ꢀ196˚C; νmax/cmꢀ1 = 3061, 1720, 1656, 1619, 1599, 1517,
1464, 1438, 1380, 1368, 1297, 1240, 1131, 1101, 1089, 1072, 1020, 998, 881, 865, 842, 811, 799,
782, 753; δH(400 MHz; CDCl3) 1.61 (s, 6H, Two 4ꢀCH3), 2.22 (m, 1H, 4aꢀH), 4.05 (t, J = 10.8 Hz,
1H, 5ꢀH), 4.28 (d, J = 5.6 Hz, 1H, 12cꢀH), 4.51 (dd, J = 10.8, J = 3.6 Hz, 1H, 5ꢀH), 5.59 (d, J = 1.2
Hz, 1H, 1ꢀH), 7.09–8.07 (m, 11H,ArꢀH); δC(100 MHz; CDCl3) 25.6, 26.3, 28.1, 36.8, 63.6, 75.0,
97.6, 115.3, 118.8, 121.9, 123.3, 124.9, 126.7, 128.1, 128.1, 128.4, 129.0, 129.5, 132.6, 135.9,
148.0, 151.6;Anal Calcd for C24H22O2: C, 84.18; H, 6.48; Found: C, 84.39; H, 6.11; m/z (ESI)
342.2[M]+.
4,4ꢀdimethylꢀ2ꢀ(naphthalenꢀ1ꢀyl)ꢀ4,4a,5,12cꢀtetrahydrobenzo[f]pyrano[3,4ꢀc]chromene (7bb).
White solid, yield 85 % (667.3 mg), mp = 214ꢀ216˚C; νmax/cmꢀ1 = 3057, 1722, 1653, 1623, 1597,
1511, 1462, 1435, 1382, 1367, 1292, 1236, 1128, 1108, 1087, 1068, 1021, 994, 884, 861, 839, 810,
796, 778, 749; δH(400 MHz; CDCl3) 1.60 (s, 3H), 1.84 (s, 3H), 2.29 (m, 1H), 4.31 (t, J = 11.2 Hz,
1H), 4.37 (d, J = 5.6 Hz, 1H), 4.62 (dd, J = 10.8, J = 3.2 Hz, 1H), 5.37 (s, 1H), 7.13ꢀ8.25 (m, 13H);
δC(100 MHz; CDCl3) 25.9, 26.4, 28.3, 37.1, 63.6, 75.6, 102.0, 115.5, 118.8, 121.9, 123.3, 125.1,
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125.5, 125.7, 126.2, 126.7, 127.3, 128.3, 128.4, 128.9, 129.0, 129.5, 131.4, 132.6, 133.8, 134.6,
149.7, 151.7;Anal Calcd for C28H24O2: C, 85.68; H, 6.16; Found: C, 85.40; H, 5.86;m/z (ESI)
392.00[M]+.
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3ꢀ(4,4ꢀdimethylꢀ4,4a,5,12cꢀtetrahydrobenzo[f]pyrano[3,4ꢀc]chromenꢀ2ꢀyl)pyridine
(7bc).
White solid, yield 82 % (563.2 mg), mp = 178ꢀ180˚C; νmax/cmꢀ1 = 3060, 3041, 1940, 1906, 1640,
1623, 1600, 1568, 1515, 1474, 1432, 1408, 1382, 1370, 1346, 1306, 1294, 1254, 1234, 1190, 1175,
1146, 1131, 1089, 1074, 1027, 1004, 991, 952, 885, 851, 810, 796, 771, 745, 718, 707, 697; δH(400
MHz; CDCl3) 1.61 (s, 6H), 2.24 (m, 1H), 4.02 (t, J = 10.8 Hz, 1H), 4.29 (d, J = 5.6 Hz, 1H), 4.53
(ddd, J = 10.8, 3.6, 1.2 Hz, 1H), 5.64 (t, J = 1.6 Hz, 1H), 7.09–8.79 (m, 10H); δC(100 MHz; CDCl3)
25.6, 26.2, 28.0, 36.7, 63.4, 75.4, 99.1, 114.8, 118.8, 121.7, 122.9, 123.4, 126.9, 128.6, 129.1,
129.5, 131.4, 132.1, 132.5, 145.8, 146.5, 149.1, 151.7;Anal Calcd for C23H21NO2: C, 80.44; H,
6.16; N, 4.08; Found: C, 80.19; H, 6.39; N, 4.31; m/z (ESI) 344.1[M+H]+.
2ꢀ(9Hꢀfluorenꢀ2ꢀyl)ꢀ4,4ꢀdimethylꢀ4,4a,5,12cꢀtetrahydrobenzo[f]pyrano[3,4ꢀc]chromene
(7bd).White solid, yield 80 % (688.9 mg), mp = 212ꢀ214˚C; νmax/cmꢀ1 = 3075, 3017, 1908, 1640,
1622, 1599, 1513, 1469, 1455, 1427, 1402, 1382, 1365, 1320, 1256, 1234, 1180, 1141, 1089, 1067,
1055, 1025, 990, 944, 906, 887, 860, 835, 818, 762, 747, 731, 699; δH(400 MHz; CDCl3) 1.47 (s,
3H), 1.65 (s, 3H), 2.24 (m, 1H), 3.88 (s, 2H), 4.10 (t, J = 11.2 Hz, 1H), 4.32 (d, J = 5.2 Hz, 1H),
4.54 (dd, J = 10.8, 2.8 Hz, 1H), 5.65 (s, 1H), 7.11–8.12 (m, 13H); δC(100 MHz; CDCl3) 25.6, 26.4,
28.2, 36.9, 36.9, 63.6, 75.1, 97.5, 115.4, 118.8, 119.5, 120.0, 121.5, 122.0, 123.3, 123.8, 125.1,
126.8, 126.8, 128.4, 129.1, 129.6, 132.7, 134.6, 141.4, 141.8, 143.2, 143.6, 148.3, 151.7;Anal
Calcd for C31H26O2: C, 86.48; H, 6.09; Found: C, 86.19; H, 6.34; m/z (ESI) 430.2[M]+.
16,16ꢀdimethylꢀ1,8c,9,10,16,16aꢀhexahydrobenzo[f]naphtho[3',4':5,6]pyrano[3,4ꢀc]chromene
(7be).White solid, yield 84 % (619.0 mg), mp = 170ꢀ172˚C; νmax/cmꢀ1 = 3061, 3034, 1949, 1894,
1801, 1637, 1609, 1580, 1494, 1458, 1430, 1382, 1366, 1300, 1272, 1251, 1242, 1147, 1116, 1088,
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(m, 1H), 2.51 (m, 3H), 4.29 (t, J = 11.2 Hz, 1H), 4.45 (d, J = 3.2 Hz, 1H), 4.55 (ddd, J = 10.8, 4,
1.2 Hz, 1H), 7.06–8.03 (m, 10H); δC(100 MHz; CDCl3) 24.8, 26.4, 26.6, 28.5, 30.0, 37.2, 63.8,
74.0, 107.7, 114.1, 118.9, 121.6, 122.8, 122.9, 126.2, 126.3, 126.8, 127.2, 128.8, 128.9, 129.0,
132.0, 134.4, 136.4, 141.8, 152.1;Anal Calcd for C26H24O2: C, 84.75; H, 6.57; Found: C, 84.54; H,
6.54; m/z (ESI) 369.2[M+H]+.
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9,9ꢀdimethylꢀ8a,9,15,15bꢀtetrahydroꢀ8Hꢀbenzo[f]indeno[2',1':5,6]pyrano[3,4ꢀc]chromene
(7bf).White solid, yield 83 % (588.4 mg), mp = 231ꢀ233˚C; νmax/cmꢀ1 = 3065, 3031, 1955, 1899,
1800, 1632, 1612, 1586, 1498, 1460, 1437, 1388, 1360, 1307, 1278, 1250, 1244, 1153, 1114, 1081,
1053, 1044, 861, 820, 768, 753, 748, 717; δH(400 MHz; CDCl3) 1.62 (s, 3H), 1.66 (s, 3H), 2.27 (m,
1H), 2.74 (d, J = 22 Hz, 1H), 3.50 (dd, J = 22.4, 2 Hz, 1H), 4.06 (t,J = 11.2 Hz, 1H), 4.52 (ddd, J =
10.8, 3.6, 1.2 Hz, 1H), 4.58 (d, J = 4 Hz, 1H), 7.07–8.19 (m, 10H); δC(100 MHz; CDCl3) 25.9,
26.1, 28.9, 36.3, 37.8, 63.3, 76.5, 112.7, 114.9, 117.3, 118.8, 122.5, 123.2, 123.6, 125.0, 126.1,
126.3, 128.6, 128.8, 129.3, 133.4, 139.1, 141.9, 148.3, 151.7;Anal Calcd for C25H22O2: C, 84.72; H,
6.26; Found: C, 84.91; H, 6.48; m/z (ESI) 355.4 [M+H]+.
Acknowledgments
We sincerely express our thanks to the Head, Department of Chemistry, S. P. University for
providing necessary research facilities. We (BDP, TRSand GCB) are grateful to the UGC, New
Delhi for research fellowships under the UGC scheme of RFSMS, and research grant under the
UGCꢀCAS program.We also thankDST, New Delhi, in general, and PURSE central facility for
massanalysis (vide sanction letter DO. no. SR/59/Zꢀ23/2010/43 dated16th march 2011).Authors
acknowledge the financial support (Project letter No. EMEQꢀ404/2014 dated 11.03.2016) of SERB,
DST, New Delhi of India.
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Supporting Information Available: Copies of1H,13C NMR spectraofall the compounds;NOESY
spectra of 7ba;Xꢀray structure and crystal data of 6af and 7ba, in CIF formatare available in
Supporting Information.This material is available free of charge via the Internet at
http://pubs.acs.org.
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