Oxy-Wittig reactions of 1-naphthyl(aryl)methylphosphonates: a new approach to naphthylarylketones

Article abstract of DOI:10.1016/j.tet.2016.02.053

Valuable compounds, naphthylarylketones are synthesized via oxy-Wittig (oxygenation of phosphonate carbanions) type reactions of diverse 1-naphthyl(aryl)methylphosphonates at room temperature by producing water soluble by-product. Commercially known but synthetically unexposed and expensive naphthylarylketones are easily synthesized using this transition metal-free, operationally simple strategy. As precursors, a range of new naphthyl(aryl)methylphosphonates are obtained in excellent yield and regioselectivity by direct and clean synthetic protocol that involves FeCl₃ or triflic acid (TfOH) mediated arylation reactions of easily accessible (hydroxy)-1-naphthylmethylphosphonate with activated as well as unactivated arenes including halogenated anisoles, biphenyl, naphthalene and pyrene (extended π-systems) at room temperature.

Full text of DOI:10.1016/j.tet.2016.02.053

Accepted Manuscript
Oxy-Wittig Reactions of 1-Naphthyl(aryl)methylphosphonates: A New Approach to
Naphthylarylketones
M.B. Zubair Khalid, Gangaram Pallikonda, R.N. Prasad Tulichala, Manab Chakravarty
PII:
S0040-4020(16)30115-6
10.1016/j.tet.2016.02.053
TET 27523
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 30 September 2015
Revised Date: 17 February 2016
Accepted Date: 23 February 2016
Please cite this article as: Zubair Khalid MB, Pallikonda G, Prasad Tulichala RN, Chakravarty M, Oxy-
Wittig Reactions of 1-Naphthyl(aryl)methylphosphonates: A New Approach to Naphthylarylketones,
Tetrahedron (2016), doi: 10.1016/j.tet.2016.02.053.
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Oxy-Wittig Reactions of 1-
Naphthyl(aryl)methylphosphonates: A
New Approach to Naphthylarylketones
M. B. Zubair Khalid, Gangaram Pallikonda, R. N. Prasad Tulichala and Manab Chakravarty*a

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Oxy-Wittig Reactions of 1-Naphthyl(aryl)methylphosphonates: A New Approach to
Naphthylarylketones
M. B. Zubair Khalid,a Gangaram Pallikonda,a R. N. Prasad Tulichalab and Manab Chakravarty*a
aDepartment of Chemistry, Birla Institute of Technology and Sciences, Pilani Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Hyderabad,
500078, INDIA.
bSchool of Chemistry, University of Hyderabad, Central University, Hyderabad-500046, India
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Valuable compounds, naphthylarylketones are synthesized via oxy-Wittig (oxygenation of
phosphonate carbanions) type reactions of diverse 1-naphthyl(aryl)methylphosphonates at room
temperature by producing water soluble by-product. Commercially known but synthetically
unexposed and expensive naphthylarylketones are easily synthesized using this transition metal-
Available online
free,
operationally
simple
strategy.
As
precursors,
a
range
of
new
naphthyl(aryl)methylphosphonates are obtained in excellent yield and regioselectivity by direct
and clean synthetic protocol that involves FeCl3 or triflic acid (TfOH) mediated arylation
reactions of easily accessible (hydroxy)-1-naphthylmethylphosphonate with activated as well as
unactivated arenes including halogenated anisoles, biphenyl, naphthalene and pyrene (extended
π-systems) at room temperature.
Keywords:
Phosphonates
Wittig
Iron(III) Chloride
Naphthalene
Ketone
2009 Elsevier Ltd. All rights reserved.
1. Introduction
also identified as very important class of compounds where the
fundamental structural scaffolds phosphonate and naphthalene
Oxygenation of phosphonate carbanions by air and/or oxygen
(oxy-Wittig reactions) can produce ketones effectively.1 Such a
process was observed previously by Horner et al. in the
autoxidation of (1-phenylalkyl)diphenylphosphine oxides during
the synthesis of symmetrical olefins from phosphonates.1f
Likewise, syntheses of nitrobenzophenone1a and anilides1g were
reported earlier by starting with the corresponding phosphonates.
In fact, the detection of chemiluminescence in autoxidation of
selected phosphonate carbanions followed by the formation of
ketones were extensively studied by the group of Motoyoshiya.1c-
were installed together as shown in Fig 1 (1a-f). Considerable
interest on the uses of 1-naphthalenemethylphosphonate (NMPA,
1a, Fig 1) and related compounds were highlighted extensively in
the literature.4-6
e
On the other hand, due to the widespread applicability of
naphthylketones in various fields,2 the synthesis of
naphthylketones3 is of significant interest to the chemists using
expensive transition metals or molecular iodine apart from the
traditional Grignard and Friedel-Crafts (FC) approaches that need
air-sensitive reagents, unsafe solvents and tedious work-up
procedure. Keeping these points in mind, we report herein the
synthesis of naphthylaryl ketones from newly developed 1-
naphthyl(aryl)methylphosphonates in the presence of KOtBu and
O2 via oxy-Wittig reactions. Curiously, these phosphonates were
Fig1.
Reported
applications
of
naphthyl(aryl)methylphosphonates
To mention a few, series of 3-phthalidyl4a and bis[(para-
methoxy)benzyl] (bis-PMB)4b esters (1b) of NMPA were
established as suitable water-stable phosphonate prodrugs with

2
Tetrahedron
ACCEPTED MANUSCRIPT
improved cell penetration property in comparison to the
result was not pleasing with 50% yield. However, in few cases,
traditional acyloxymethyl phosphonate prodrugs. Asymmetric
synthesis of the naphthyl phosphonate system was also well
studied in the literature.4c Further, as osteoclastic acid
phosphatase (OAP) inhibitors, α-aryl substituted compounds of
type 1d was proved to be favoured for the treatment of
osteoporosis, a bone strength-reducing disease.6a-b Another α-
substituted compounds of type 1e (1-naphthyl) were identified as
plant and mammal purple acid phosphatase (PAP) inhibitors.6c
Additionally, a reasonable hydrophobic character of naphthalene
skeleton helped the group of 2-naphthylmethylphosphonates of
type 1f to exhibit the affinity to the luminal phosphate and
contraluminal p-aminohippurate/sulfate transporters.7
the expected products (3f-j and 3o, entries 5,6 & 10, Table 1)
were obtained in moderate to good yields only by using TfOH.
As this reaction was favored at rt, the need of much excess arene
as reagent or solvent was circumvented. Likewise,
regioselectivity being a major issue for the FC type approach,
neat reactions of other unactivated arenes such as toluene and o-
xylene with 2a were focused and that produced the expected
products 3b and 3c respectively in admirable yields (85-90%)
and regioselectivity (99:1). In an analogous manner, 3d was
obtained as expected using mesitylene. In case of activated arene
like anisole, the regioselectivity became relatively lower (~85:15)
as observed for the compound 3e (entry 5; Table 1). Notably, an
alternative synthetic process for compound 3e (1-naphthyl) along
with its 2-naphthyl isomer (as a mixture) were reported earlier
Hence, due to the wide variety of applications, a
convenient synthesis of naphthyl phosphonate systems offer
significant prospective. Therefore, we surveyed the synthetic
methodologies for the key intermediates phosphonate esters of
these compounds that are traditionally prepared by
Arbuzov/Pudovik reactions with several limitations. In particular,
syntheses of α-aryl/alkyl substituted compounds of type 1d could
be accomplished via Arbuzov reactions but the accessibility and
reactivity of the secondary halides are considerably challenging.
Therefore, the synthetic methods for the related compounds are
sporadically mentioned in the literature.6 The reported attempt
started with a primary 1-naphthylhalide followed by substitution
reactions in the presence of a base (like n-BuLi).6a Furthermore,
(1-naphthyl)benzyl phosphonate was resulted in poor yield
when naphthalene was used as arene.9a
Table 1 Acid mediated arylation reactions of α-hydroxy phosphonate
(2)a
(22.5%)
by
the
photolysis
of
1-
naphthyl(phosphonyl)diazomethane in benzene.8a Another
pioneering route is recently reported via Pd-catalysed α-arylation
reaction of benzylic phosphonates with 1-naphthyl bromide.8b
Therefore, invention of an economic, efficient and operationally
simple synthetic route to these phosphonates is still meaningful.
In this aspect, our previous attempt via acid mediated Friedel-
Crafts (FC) reactions of electron-rich α-hydroxyphosphonates
with naphthalene (as arene) was partly successful9 because the
reactivity of naphthalene and the required reaction conditions led
to the isomeric mixture of 1-naphthyl or 2- naphthyl
phosphonates which was very much tiresome to separate. Herein,
we report a straightforward and simple synthetic strategy to
generate new α-arylated naphthalene based phosphonates as
precursors to afford naphthylarylketones. Unlike previous
reports, the other significant arenes such as haloanisoles,
thiophene, biphenyl and pyrene are also explored for these
reactions and the corresponding naphthylaryl ketones are
obtained.
2. Results/Discussion
a
First, we dealt with the synthesis of phosphonates 3a-o
(Table 1) from easily accessible 1-naphthyl α-hydroxy
phosphonates (2a-b) by following our recently reported synthetic
protocol where Lewis acid mediated nucleophilic substitutions
are feasible for allylic and electron-rich benzylic phosphonates
without prefunctionalization of α-hydroxy phosphonates.9 For the
selection of acids, most accessible and inexpensive FeCl3 was
preferred based on previous results.9a,10 Our initial effort using
benzene as an unactivated arene (1.4 equiv) gave fruitful result to
produce 3a (Table 1, entry 1) under (additional) solvent-free
conditions at room temperature in the presence of FeCl3.
Although TfOH also could be a choice9b (Table S1 in SI) but the
Reaction Conditions: 2 (1 equiv) and for compounds (i) 3a-e: arene (1.4
equiv) and FeCl3 (1 equiv). (ii) 3f-j, arene (1 equiv), TfOH (1 equiv) and
DCE (3 mL) (iii) 3k-n: FeCl3 (1 equiv), arene (1 equiv) and DCE (3 mL)
were used.(iv) 3o: same as 3f-i
b Isolated yield after chromatography.
c Determined by 1H NMR integration.
___________________________________________________
Further, the non-activated 4-iodoanisole was treated with 2a in
1,2-dichloroethane (DCE) under FeCl3 mediated approach where
compound 3f was produced only in 40% yield. Keeping the other
parameters intact, the yield was improved up to 80% by replacing
FeCl3 with TfOH (see Table S1 in SI). In fact, other halogenated
arenes such as 4-bromoanisole, 4-chloroanisole, 4-fluoroanisole

3
and 3-bromoanisole could produce desired products 3g-j
respectively in moderate to good yields at room temperature by
using TfOH but not FeCl3. In fact, halogenated compounds, in
particular, 3f-g and 3j should be suitable precursors for further
derivatization through well-established C-C or C-N coupling
reactions and that can widen the future scope of these
halogenated compounds synthesized herein.
Even, thiophene (a heteroarene) also gave a promising
result to produce 3k in good yield (70%) and regioselectivity
(88:12). The extensive applications of π-conjugated materials11
encouraged us to examine the reactivity of polycyclic biphenyl,
naphthalene, anthracene and pyrene. Biphenyl gave the mono-
substituted compound 3l efficiently with substantial yield and
regioselectivity (entry 8, table 1) and the compound 2a was
arylated with naphthalene to generate a mixture (50:50) of both
thermodynamically (1-naphthyl) and kinetically (2-naphthyl)
controlled products of type 3m (entry 9, table 1).
Disappointingly, the attempt to afford the analogous anthracenyl
naphthyl phosphosphonate was unsuccessful.12
4e was isolated as single isomer by starting with regioisomeric
ACCEPTED MANUSCRIPT
mixture (~85:15) of 3e. It is worth noting a few literature reports
where conformational analysis for mesityl-1-naphthylketone 4d
was of special interest2c and compound 4e was utilized for
synthesizing anti-hyperglycemic agents by the dissociation of O-
CH3 bond by the treatment of BBr3 followed by substitution
reactions in the presence of base.2g The compound 4e was also
chosen as origin to produce a novel class of anti-implantation
agents.2h In addition, the backbone with thioanisole analogue of
4e was reported to be an effective anticancer agent.2b Such a
useful ketone was primarily synthesized by polyphosphoric acid
mediated condensation of 1-naphthoic acid with anisole at
elevated temperature (80 oC).2g-h
Table 2 Conversions of phosphonates to ketonesa
While ethoxy group is one of the most used substituents in
organophosphonate chemistry, choice of methoxy could be much
more economical. It is also worth noting the earlier mentioned
report that showed different result for the Pd-catalyzed α-
arylation of benzylic phosphonates by changing the alkoxy
groups.8b Nevertheless, the replacement of 2a with 2b offered
almost the same result by producing 3n (entry 9, Table 1).
Furthermore, the phosphonate (3o), connected with both pyrene
and naphthalene core, was effectively synthesized from the
reaction of 2b with pyrene (entry 10, Table 1).
To verify the scalability, products 3a-e were obtained in the
same yield when the reaction was performed with arenes and 2a
in 13 mmol scale. However, the scope of this strategy is not
extendable for completely electron-deficient arenes.
Next,
by
considering
utmost
importance
of
naphthylarylketones,2-3 most of the above phosphonates are
utilized to access the naphthylarylketones via oxy-Wittig type
reaction. To date, this strategy has not been explored to afford
naphthylaryl ketones. In this current approach, necessities of
expensive metals, harsh reaction conditions and air/oxygen
sensitive reagents or solvents were completely avoided. Based on
the literature report,1 we started the oxy-Wittig reaction for the
phosphonate 3a by using KOtBu (base) and DMF (solvent) under
oxygen balloon to afford the ketone 4a (entry 1, Table 2) and the
conversion was almost quantitative after 1.5 h (isolated yield:
90%). The conversion was relatively poor (60%) and required
duration was more (4 h) when the reaction was performed only in
air. Other easily accessible and cheap bases like NaH and K2CO3
(Table S2 in SI) were also screened where NaH worked in equal
efficacy to KOtBu. Another base n-BuLi could also be a choice1b
but to make our process operationally simple and easy, air-stable
KOtBu was preferred. Although these reactions were carried out
by starting with the mixture of regioisomers (99:1) for 3b and 3c,
the corresponding products 4b and 4c (entries 2-3, Table 2) were
isolated in single isomeric form with 90% and 85% yields
respectively. Notably, synthesis of compound 4b was majorly
reported via Pd-catalyzed based methodology13a and synthetic
procedure for compound 4c is not available in the literature till
date and also seems to be very expensive.13b The naphthylaryl
ketones 4d-e (entries 4-5, Table 2) having electron donating
substituents were isolated in moderate yield. Of note, the ketone
aReaction Conditions: 3 (1 equiv), KOtBu (4 equiv) in DMF (2 mL/ mmol)
using an oxygen balloon.
bIsolated yield after chromatography.
c Determined by 1H NMR integration.
d 6 equiv of KOtBu was used.
The haloanisole substituted naphthyl ketones 4f-h were afforded
fruitfully in
a similar manner from the corresponding
phosphonates. Notably, the compound 4g, attached with the most
electron withdrawing substituent (-F), was obtained in excellent
yield (92%). The existence of halide moiety with ketones 4f and
4h can extend the further scope widely as mentioned before. No
synthetic routes are available for compounds 4f-h in the
literature. However, these compounds may be available from
limited chemical vendors.14 The compound 1-naphthyl-2ʹ-thienyl
ketone 4i was also synthesized using a similar method in
moderate yield (entry 8, Table 2) and this ketone is known to be
used in the literature for the synthesis of likely biologically active
compounds.15 The established synthetic route for 4i includes the
FC reaction of thiophene with air-sensitive and hazardous
naphthoyl chloride and SnCl4.15 Further, ketones with
naphthalene, biphenyl or pyrene core are well recognized for

4
Tetrahedron
ACCEPTED MANUSCRIPT
studying aromatic stacking interactions16b and phase
3. Conclusion
transitions.16c Hence, the extended π-conjugated naphthylaryl
ketones 4j-l were synthesized effectively in a simple way by
starting with 3l, 3m or 3n and 3o respectively. Notably, the only
report for the synthesis of 4j is known with 65% yield via Pd–
catalyzed coupling reactions of biphenylboronic acid with
carboxylic phosphoric anhydride.16a Being an important
overcrowded bichromophoric system, dinaphthylketone 4k is an
important substrate in organic and structural chemistry and these
compounds are mainly produced by FC approach.17 In this
perspective, our approach should be meaningful and
advantageous. We have converted both 3m and 3n to produce the
compound 4k as a regioisomeric mixture (50:50) in efficient
yield (entry 10, Table 2). However, during the purification
through column chromatography, the only isomer naphthalene-1-
yl(naphthalene-2-yl)methanone 4kʹ was crystallized out from the
eluent [EtOAc/ Hexane: 1:99] and isolated in pure isomeric form.
Although the ketone 4l is known in the literature, no fruitful
information on the synthesis and reactions are available.19
In conclusion, FeCl3 or TfOH mediated efficient regioselective
synthetic approach is developed from the reactions of (hydroxy)-
1-naphthylmethylphosphonate with both activated/unactivated
arenes including haloanisoles to afford valuable 1-
naphthyl(aryl)methylphosphonates preferably under (additional)
solvent-free conditions at room temperature, which relates to
minimize the energy consumption. The scope for utility of these
phosphonates
was
extended
to
the
synthesis
of
naphthylarylketones in moderate to excellent yield through oxy-
Wittig type reactions. It offers an alternative, convenient and
economical approach for a range of synthetically and biologically
useful ketones.
4. Experimental Section
General Comments. Solvents were purified by distillation from
appropriate drying agents under nitrogen atmosphere. Organic
extracts were dried over anhydrous sodium sulfate. Solvents were
removed in a rotary evaporator under reduced pressure. Silica gel
(100-200 mesh size) was used for the column chromatography.
Reactions were monitored by TLC on silica gel 60 F254 (0.25
The scalability was also checked for these reactions by
selecting the synthesis of important ketone 4j that was
conveniently prepared with the reported yield by starting with the
phosphonate 3l in 5 mmol scale.
1
mm). H, 13C, and 31P NMR spectra (1H, 400 or 500 MHz; 13C,
101 or 126 MHz; 31P, 162 or 201 MHz) were recorded using a
400 or 500 MHz spectrometer in CDCl3 with shifts referenced to
SiMe4 ( δ = 0) or 85% H3PO4 ( δ = 0). IR spectra were recorded
on an FT-IR spectrophotometer. Melting points were determined
by using a local hot-stage melting point apparatus and are
uncorrected. Elemental analyses were carried out on a FLASH
EA 1112 Series CHN analyzer from School of Chemistry,
University of Hyderabad. Mass spectra were recorded using
LC/MS and HR/MS equipment. Syntheses for compounds 2a6a
and 2b18 was prepared by following the method reported in the
literature.
Based on the literature report9-10 and our experimental
observations, the aryl substitution on naphthyl phosphonate
system (table 1) presumably proceeds through the formation of
relatively
stable
naphthylicphosphonium
carbocation
intermediate. To understand the formation of ketone (table 2), a
careful mechanistic study on the oxy-Wittig reaction was
reported previously in the literature.1c Thus, a possible reaction
mechanism for the formation of naphthylarylketones is illustrated
in scheme 1.
Procedure
for
the
synthesis
of
(1-
naphthyl)arylmethylphosphonates (3a-e)
To a mixture of 2a (0.500 g, 1.699 mmol) in benzene (0.185 gm,
2.378 mmol), FeCl3 (0.275 gm, 1.699 mmol) was added at room
temperature and then the reaction mixture was stirred at rt for 6 h.
After completion of the reaction as indicated by TLC, the mixture
was quenched with water. The aqueous layer was extracted with
ethyl acetate (3 x 25 mL). The organic layer is evaporated under
vacuum and product is purified by column chromatography using
ethyl acetate/ petroleum ether (40/60) as the eluent to afford 3a
(0.54 g, 90%) as colourless liquid. Unless otherwise stated, all
the other compounds 3b-e were prepared analogously using
similar molar quantities of arenes, phosphonate and FeCl3.
Diethyl (naphthalen-1-yl(phenyl)methyl)phosphonate (3a); Rf
(38% EtOAc/Hexane) 0.45; νmax (KBr) 3080, 2981, 1596, 1247,
1025, 780 cm−1; δH (400 MHz, CDCl3) 1.06 (3H, t, J 8.0 Hz,
OCH2CH3), 1.18 (3H, t, J 8.0 Hz, OCH2CH3), 3.81-4.05 (4H, m,
OCH2CH3), 5.34 (1H, d, J 24.0 Hz, CH(P)Ar2), 7.20-7.33 (3H,
m, Ar-H), 7.44-7.62 (5H, m, Ar-H), 7.80 and 7.87 (2H, d, J 8.0
Hz each, Ar-H), 8.12 (1H, d, J 8.0 Hz, Ar-H), 8.30-8.34 (1H, m,
Ar-H); δC (101 MHz, CDCl3) 16.2 and 16.3 (d, J 6.1 Hz each),
45.9 (d, J 140.4 Hz), 62.7 and 62.8 (d, J 6.1 Hz each), 123.1,
125.4, 125.5, 126.4, 127.1 (d, J 2.0Hz), 127.6 (d, J 6.1Hz), 128.0,
128.5 (d, J 7.1Hz), 129.0, 129.7 (d, J 7.1 Hz), 131.7 (d, J 12.1
Hz), 132.6 (d, J 3.0Hz), 134.17, 136.6 (d, J 6.1 Hz); δP (162
Scheme 1 Plausible reaction mechanism for the conversion of
phosphonates to ketones; M= Na or K.
The phosphonate forms a carbanion of type A and then gradually
it generates the likely high energy intermediate phospha-1,2-
dioxetane (B) via peroxide formation as evidenced by
Motoyoshiya et al.1c Finally this intermediate B breaks into the
generation of ketone along with the formation of phosphate C
that is partly supported by the peak at δ -0.28 in 31P NMR for the
reaction mixture of compound 3a with KOtBu/DMF in the
presence of oxygen balloon. Subjected to this mechanism,
comparatively lower yields for ketones 4d-f could be possibly
linked with the stability of carbanionic intermediate A that are
relatively unstable for the corresponding phosphonates due to the
+I or energetically unfavorable resonance effect. Again,
relatively higher yield of 4g (fluoro containing ketone) compared
to 4f and 4h support the formation of intermediate A (Scheme 1).

5
MHz, CDCl ) 25.7; LC/MS: m/z 355 [MH+]; HRMS (ESI): MH+,
found 355.1447. C21H24O3P requires 355.1458.
1607, 1250, 1026; δ (400 MHz, CDCl ) 1.06 (3H, t, J 7.1 Hz,
ACCEPTED MANUSCRIPT
3
H
3
OCH2CH3), 1.20 (3H, t, J 7.1 Hz, OCH2CH3), 3.71 (3H, s,
OCH3), 3.81-3.92 (2H, m, OCH2CH3), 4.03-4.08 (2H, m,
OCH2CH3), 5.30 (1H, d, J 26.5 Hz, CH(P)Ar2), 6.84 (2H, d, J 8.7
Hz, Ar-H), 7.42-7.56 (5H, m, Ar-H), 7.82 and 7.83 (2H, dd, J 8.2
Hz each, Ar-H), 8.10 (1H, d, J 8.4Hz, Ar-H), 8.29 (1H, d, J 7.0
Hz, Ar-H); The other peak for another isomer at δH 6.01 (d, J
26.0 Hz) was clearly observed. δC (101 MHz, CDCl3) 16.2 and
16.3 (d, J 5.8 Hz each), 44.9 (d, J 141.0 Hz), 55.1, 62.6 and 62.8
(d, J 6.0 Hz each), 113.9, 123.2, 125.5 (d, J 9.0 Hz), 126.4, 127.4
(d, J 6.5 Hz), 127.9 (d, J 0.97 Hz), 128.5 (d, J 6.4 Hz), 129.1,
130.7 (d, J 7.2Hz), 131.6, 131.7, 132.9 (d, J 2.2 Hz), 134.2, 158.7
(d, J 2.6 Hz), peaks for another isomer at δ 36.7 (d, J 146.9 Hz)
and 55.7 were clearly observed; δP (162 MHz, CDCl3) 26.1, peak
for another isomer at δP 26.6 also appeared; LC/MS: m/z 385
[MH+]; HRMS (ESI): MH+, found 385.1545. C22H26O4P requires
385.1563.
Diethyl (naphthalen-1-yl(p-tolyl)methyl)phosphonate (3b).
The compound 3b (0.562g, 90%) was isolated as a mixture of
regioisomer (o/p 1:99, colourless liquid); Rf (40%
EtOAc/Hexane) 0.45; νmax (KBr) 2979, 1509, 1395, 1244, 1051,
967; δH (400 MHz, CDCl3) 1.10 (3H, t, J 7.0 Hz, OCH2CH3),
1.20 (3H, t, J 8.0 Hz, OCH2CH3), 2.30 (3H, s, CH3-Ar), 3.80-
4.07 (4H, m, OCH2CH3), 5.30 (1H, d, J 28.0 Hz, CH(P)Ar2), 7.12
(2H, d, J 8.0 Hz, Ar-H), 7.44-7.57 (5H, m, Ar-H), 7.79 and 7.87
(2H, d, J 8.0 Hz each, Ar-H), 8.11 (1H, d, J 8.0 Hz, Ar-H), 8.28
(1H, d, J 8.0 Hz, Ar-H); δC (101 MHz, CDCl3) 16.2 and 16.3 (d,
J 6.1 Hz each), 21.0, 45.5 (d, J 140.4 Hz), 62.7 (d, 7.1 Hz),
123.1, 125.4 (d, J 1.0 Hz), 125.5, 126.5, 127.5 (d, J 6.1Hz),
127.9, 129.0, 129.23, 129.5 (d, J 8.1Hz), 131.7 (d, J 12.1Hz),
132.8 (d, J 3.0Hz), 133.5 (d, J 7.1Hz), 134.26, 136.7 (d, J 3.0
Hz); δP (162 MHz, CDCl3) 25.9; LC/MS: m/z 369 [MH+]; HRMS
(ESI): MH+, found 369.1600. C22H26O3P requires 369.1614.
Diethyl
((5-iodo-2-methoxyphenyl)(naphthalen-1-
yl)methyl)phosphonate (3f). To a solution of 2a (0.500 g, 1.699
mmol) in dichloroethane (3 mL), 4-iodoanisole (0.398 g, 1.699
mmol) followed by TfOH (0.254 g, 1.699 mmol) were added at
room temperature and the reaction mixture was stirred for 4 h.
Here, the work up procedure was carried out using
dichloromethane and the desired compound 3f (0.693g, 80%)
was isolated as a mixture of regioisomer (84:16, brown solid);
Diethyl
(3,4-dimethylphenyl)(naphthalen-1-
yl)methyl)phosphonate (3c). The compound 3c (0.551g, 85%)
was isolated as a mixture of regio-isomer (o/p 1:99, colourless
liquid); Rf (42% EtOAc/Hexane) 0.43; νmax (KBr) 3045, 2978,
1507, 1247, 1027, 953; δH (400 MHz, CDCl3) 1.04 (3H, t, J 7.1
Hz, OCH2CH3), 1.20 (3H, t, J 7.1 Hz, OCH2CH3), 2.19 (3H, s,
CH3-Ar), 2.22 (3H, s, CH3-Ar), 3.76-4.06 (4H, m, OCH2CH3),
5.26 (1H, d, J 26.4 Hz, CH(P)Ar2), 7.06 (1H, d, J 7.6 Hz, Ar-H),
7.31-7.55 (5H, m, Ar-H), 7.78-7.86 (2H, m, Ar-H), 8.12 (1H, d, J
8.5Hz, Ar-H), 8.24-8.27 (1H, m, Ar-H); δC (101 MHz, CDCl3)
16.1 and 16.3 (d, J 5.8 Hz each), 19.3, 19.8, 45.0 (d, J 125.5 Hz),
62.7 (d, J 6.0 Hz), 123.2, 125.4, 126.3, 127.0, 127.1, 127.6 (d, J
7.1 Hz), 127.8, 129.0, 129.7 (d, J 2.0 Hz), 130.8 (d, J 7.5 Hz),
131.8 (d, J 11.6 Hz), 132.9 (d, J 2.8 Hz), 133.9 (d, J 6.0 Hz),
134.2, 135.4 (d, J 2.8 Hz), 136.5 (d, J 1.9 Hz); δP (201 MHz,
CDCl3) 25.9; LC/MS: m/z 383 [MH+]; HRMS (ESI): MH+, found
383.1764. C23H28O3P requires 383.1771.
o
mp 110-112 C; Rf (55% EtOAc/Hexane) 0.48; νmax (KBr) 3051,
2927, 1657, 1479, 1253, 1018; δH (400 MHz, CDCl3) 1.06 and
1.19 (3H each, two sets triplet, J 7.1 Hz each, OCH2CH3), 3.76-
3.86 (1H, m, OCH2CH3), 3.91 (3H, s, OCH3), 3.94-4.08 (3H, m,
OCH2CH3), 5.85 (1H, d, J 26.2 Hz, CH(P)Ar2), 6.66 (1H, dd, not
well resolved, J 8.6 Hz, 0.7 Hz, Ar-H), 7.47-7.55 (4H, m, Ar-H),
7.78-7.86 (2H, m, not well resolved, Ar-H), 7.97 (1H, s, Ar-H),
8.16-8.21 (2H, m, Ar-H); the other peaks appeared due to the
other isomer. δC (126 MHz, CDCl3) 16.2 and 16.3 (each set d, J
5.7 Hz each), 36.6 (d, J 143.0 Hz), 55.9, 62.6 and 62.8 (d, J7.1
Hz each), 83.2 (d, J 3.2 Hz), 102.9 (d, J 1.4 Hz), 123.3, 125.5,
126.2, 127.7 (d, J 6.3Hz), 127.9 (d, J 1.6 Hz), 128.2 (d, J 5.3 Hz),
128.8, 130.6 (d, J 6.6 Hz), 132.0 (d, J 11.3 Hz), 132.9 (d, J
2.8Hz), 134.0, 137.2 (d, J 2.5 Hz), 139.2 (d, J 5.3 Hz), 156.4 (d, J
8.4 Hz); δP (162 MHz, CDCl3) 25.5; the other peak at δP 25.1
appears due to other regioisomer; LC/MS: m/z 511 [MH+];
HRMS (ESI): MH+, found 511.0524. C22H25IO4P requires
511.0530.
Diethyl (mesityl(naphthalen-1-yl)methyl)phosphonate (3d).
The compound 3d (0.572g, 85%) was isolated as white solid; mp
122 -124 C; Rf (45% EtOAc/Hexane) 0.42; νmax (KBr) 3058,
o
2981, 1600, 1472, 1237, 1027, 962, 769; δH (400MHz, CDCl3)
1.16 (3H, t, J 8.0 Hz, OCH2CH3), 1.33 (3H, t, J 8.0 Hz,
OCH2CH3), 2.03 (3H, s, CH3-Ar), 2.24 (3H, s, CH3-Ar), 2.82
(3H, s, CH3-Ar), 3.52-3.60 (1H, m, OCH2CH3), 3.95-4.00 (1H,
m, OCH2CH3), 4.17-4.29 (2H, m, OCH2CH3), 5.48 (1H, d, J 28.0
Hz, CH(P)Ar2), 6.66 (1H, s, Ar-H), 7.02 (1H, s, Ar-H), 7.28-7.40
(2H, m, Ar-H), 7.52-7.60 (2H, m, Ar-H), 7.80-7.82 (2H, m, Ar-
H), 8.58 (1H, d, J 8.0 Hz, Ar-H); δC (101MHz, CDCl3) 16.3 and
16.4 (d, J 6.0 Hz each), 20.8, 21.9, 22.2, 44.0 (d, J 141.4 Hz),
61.8 (d, J 7.1 Hz), 63.1 (d, J 7.1 Hz), 123.7, 124.9, 125.2, 125.9,
127.8, 128.9, 129.4 (d, J 6.7 Hz), 129.8, 130.2 (d, J 6.7 Hz),
131.7, 132.5 (d, J 15.5 Hz), 133.19, 134.0 (d, J 2.22 Hz), 136.5
(d, J 5.5 Hz); δP (162MHz, CDCl3) 27.0; LC/MS: m/z 397
[MH+]; HRMS (ESI): MH+, found 397.1910. C24H30O3P requires
397.1927.
Diethyl
((5-bromo-2-methoxyphenyl)(naphthalen-1-
yl)methyl)phosphonate (3g).
This reaction was performed in a manner similar to the synthesis
of compound 3f using 4-bromoanisole. The compound 3g (50%,
0.393g) was isolated as a mixture of regioisomers (97:3,
colourless liquid); [Found: C, 56.96; H, 5.14. C22H24BrO4P
requires C, 57.03; H, 5.22%]; Rf (58% EtOAc/Hexane) 0.47; νmax
(KBr) 2980, 1599, 1488, 1247, 1026, 964, 774; δH (500MHz,
CDCl3) 1.03 and 1.16 (3H each, t, J 7 Hz each, OCH2CH3), 3.77-
3.81 (1H, m, OCH2CH3), 3.89 (3H, s, OCH3), 3.90-4.06 (3H, m,
OCH2CH3), 5.86 (1H, d, J 26.2 Hz, CH(P)Ar2), 6.74 (1H, dd, J
8.8 Hz, 1.0H, Ar-H), 7.26-7.29 (1H, m, Ar-H), 7.42-7.52 (3H, m,
Ar-H), 7.76-7.83 (3H, m, Ar-H), 8.15 (1H, d, J 8.5 Hz, Ar-H),
8.19-8.21 (1H, m, Ar-H); δC (126MHz, CDCl3) 16.1 and 16.2 (d,
J 5.8Hz each), 36.8 (d, J 142.8 Hz), 56.0, 62.6 and 62.8 (d, J 7.1
Hz each), 112.3, 113.2 (d, J 3.1Hz), 123.3, 125.4, 125.5, 126.2,
127.7 (d, J 6.3 Hz), 127.8 (d, J 5.2 Hz), 127.9 (d, J 1.4 Hz),
Diethyl
((4-methoxyphenyl)(naphthalen-1-
yl)methyl)phosphonate (3e).9a The compound 3e (0.522g, 80%)
was isolated as a mixture of regioisomer (o/p 15:85, colourless
liquid); Rf (50% EtOAc/Hexane) 0.50; νmax (KBr) 3063, 2980,

6
Tetrahedron
ACCEPTED MANUSCRIPT
128.9, 131.1 (d, J 2.5 Hz), 132.0 (d, J 11.4 Hz), 132.9 (d, J 2.9
Ar-H), 7.80-7.83 (1.4H, m, Ar-H), 8.15-8.19 (1.8H, m, Ar-H),
Hz), 133.5 (d, J 5.2 Hz), 134.1, 155.6 (d, J 8.5 Hz); δP (162MHz,
8.24 (1H, d, J 8.5 Hz, Ar-H); δC (126MHz, CDCl3) 16.1, 16.2,
16.3 (three doublets, J 6.0 Hz each), 36.6 (d, J 143.1 Hz), 43.6
(d, J 142.1 Hz), 55.5, 56.1, 62.6, 62.7, 62.8 (three doublets, J 7.0
Hz each), 113.6 (d, J 2.4 Hz), 114.3, 118.3, 121.6 (d, J 3.2 Hz),
123.3, 123.9, 124.7 (d, J 4.1 Hz), 125.3 (d, J 2.0 Hz), 125.4 (d, J
2.0 Hz), 125.5, 125.55, 125.58, 125.7, 126.2, 126.3, 127.6 (d, J
6.3 Hz), 127.8 (d, J 6.5 Hz), 127.9 (d, J 2.1 Hz), 128.1 (d, J 1.6
Hz), 128.2 (d, J 4.9 Hz), 128.8, 128.9, 131.1, 132.0, 132.1, 132.2
(d, J 4.9 Hz), 132.7 (d, J 2.7Hz), 133.0 (d, J 2.6 Hz), 134.0,
134.1, 157.1 (d, J 8.7 Hz), 159.0 (d, J 2.1 Hz); LC/MS: m/z 463
[MH+] and 465 [MH+2]+ (1:1); HRMS (ESI): MH+ and [MH+2]+
found 463.0648 and 465.0629. C22H25BrO4P requires 463.0674
and 465.0668.
CDCl3) 25.68; LC/MS: m/z 463 [MH+] and 465 [MH+2]+ (1:1);
Diethyl
yl)methyl)phosphonate (3h).
((5-chloro-2-methoxyphenyl)(naphthalen-1-
This reaction was performed for 5h in a manner similar to the
synthesis of compound 3f-g. The compound 3h (0.320 g, 45%) is
isolated as a mixture of regioisomer (97:3, pale yellow solid); mp
110-112 oC; Rf (50% EtOAc/Hexane) 0.45; νmax (KBr) 2980,
1486, 1252, 1022, 962, 775; δH (500 MHz, CDCl3) 1.05 and 1.18
(3H each, two sets triplet, J 7.1 Hz each, OCH2CH3), 3.81-3.88
(1H, m, OCH2CH3), 3.92 (3H, s, OCH3), 3.95-4.07 (3H, m,
OCH2CH3), 5.89 (1H, d, J 26.2 Hz, CH(P)Ar2), 6.81 (1H, d, J 8.8
Hz, Ar-H), 7.16 (1H, ddd, J 8.7, 2.5, 1.7 Hz, Ar-H), 7.46-7.54
(3H, m, Ar-H), 7.69-7.70 (1H, m, Ar-H), 7.79 (1H, d, J 8.1 Hz,
Ar-H), 7.85 (1H, dd, J 8.0, 1.2 Hz, Ar-H), 8.18 (1H, d, J 8.4 Hz,
Ar-H), 8.24 (1H, dd, J 7.6, 1.4 hz, Ar-H); δC (126 MHz, CDCl3)
16.2 and 16.3 (each set d, J 6.0 Hz each), 36.8 (d, J 142.7 Hz),
56.1, 62.6 and 62.8 (d, J 7.1 Hz each), 111.8, 123.3, 125.5 (d, J
1.4 Hz), 125.51, 125.8 (d, J 3.1 Hz), 126.2, 127.3 (d, J 5.0 Hz),
127.6 (d, J 6.2 Hz), 127.9, 128.1 (d, J 2.1 Hz), 128.9, 130.7 (d, J
5.2 Hz), 132.0 (d, J 11.3 Hz), 132.9 (d, J 2.6 Hz), 134.1, 155.1
(d, J 8.3 Hz); δP (162 MHz, CDCl3) 25.1; LC/MS: m/z 419
[MH+] and 421 [MH+2]+ (3:1); HRMS (ESI): MH+, found
419.1165. C22H25ClO4P requires 419.1173.
Diethyl (naphthalen-1-yl(thiophen-2-yl)methyl)phosphonate
(3k). The compound 3k (0.428g, 70%) was synthesized using a
similar procedure to compound 3a by using 1 equiv thiophene, 1
equiv FeCl3 and DCE (3 mL) as a solvent. This compound was
isolated as a mixture of regioisomers (88:12, colourless solid);
o
mp: 58-60 C; Rf (49% EtOAc/Hexane) 0.48; νmax (KBr) 3442,
2981, 1595, 1251, 1020; δH (400 MHz, CDCl3) 0.96 (3H, t, J 7.1
Hz, OCH2CH3), 1.25 (3H, t, J 7.1 Hz, OCH2CH3), 3.64-4.15 (4H,
m, OCH2CH3), 5.60 (1H, d, J 26.7 Hz, CH(P)Ar2), 6.96-6.98
(1H, m, Ar-H), 7.19 (1H, d, J 6 Hz, Ar-H), 7.29-7.30 (1H, m, Ar-
H), 7.48-7-58 (3H, m, Ar-H), 7.83 and 7.79 (2H, d, J 8.0 Hz
each, Ar-H), 8.14-8.17 (2H, m, Ar-H); The peak at δH 5.45 (d, J
26.0 Hz) is due to other isomer. δC (126MHz, CDCl3) 16.1 and
16.3 (d, J 5.7 Hz each), 40.6 (d, J 142.8 Hz), 62.9 and 63.1 (d, J
7.2 Hz each), 122.9, 124.9 (d, J 2.7 Hz), 125.5 (d, J 2.0 Hz),
125.6, 126.5, 126.8 (d, J 2.3 Hz), 127.4 (d, J 7.6 Hz), 127.6 (d, J
5.8 Hz), 128.2 (d, J 2.2 Hz), 129.1, 131.4 (d, J 7.4 Hz), 132.5 (d,
J 3.7 Hz), 134.0, 139.3 (d, J 5.6 Hz); δP (162 MHz, CDCl3)
23.961, 25.031; LC/MS: m/z 361 [MH+]; HRMS (ESI): MNa+,
found 383.0823. C19H22O3PSNa requires 383.0841.
Dimethyl
yl)methyl)phosphonate (3i).
((5-fluoro-2-methoxyphenyl)(naphthalen-1-
This reaction was carried out for 4h in a manner similar to the
synthesis of compound 3f-h. The compound 3i (0.318 g, 45%) is
isolated as a pale yellow liquid; [Found: C, 64.23; H, 5.31.
C20H20FO4P requires C, 64.17; H, 5.39]; Rf (40% EtOAc/Hexane)
0.35; νmax (KBr) 3441, 2924, 1737, 1598, 1248, 1030, 964, 780;
δH (400 MHz, CDCl3) 3.56 (3H, d, J 10.7 Hz, POCH3), 3.64 (3H, d,
J 10.7 Hz, POCH3), 3.92 (3H, s, Ar-OCH3), 5.95 (1H, d, J 26.2 Hz,
CH(P)Ar2), 6.81-6.89 (2H, m, Ar-H), 7.53-7.55 (4H, m, Ar-H), 7.79-
7.84 (2H, m, Ar-H), 8.17-8.25 (2H, m, Ar-H); δC (101 MHz, CDCl3)
36.6 (d, J 142.6 Hz), 53.4 and 53.5 (d each, J 3.4 Hz each), 111.6
(dd, J 8.3, 1.5 Hz), 114.6 (dd, J 23.0, 2.6 Hz), 117.8 (dd, J 24.5, 5.2
Hz), 123.2, 125.5 (d, J 1.8 Hz), 125.6, 126.4, 126.7 (dd, J 7.5, 5.5
Hz), 127.5 (d, J 6.3 Hz), 128.1 (d, J 1.4 Hz), 128.9, 131.9 (d, J 11.5
Hz), 132.8 (d, J 2.8 Hz), 134.1, 152.6 (dd, J 8.6, 2.2 Hz), 156.9 (dd,
J 239.0, 3.1 Hz); δP (162 MHz, CDCl3) 28.1(d, J 1.3 Hz); LC/MS
m/z 375 [MH+].
Diethyl
[1,1’-biphenyl]-4-yl(naphthalene-1-
yl)methyl)phosphonate (3l). The compound 3l (0.585g, 80%,
p/o 99:1) was synthesized in a fashion analogous to 3k and
isolated as colourless solid; mp 118-120 oC; [Found: C, 75.42; H,
6.38. C27H27O3P requires C, 75.33; H, 6.32%]; Rf (50%
EtOAc/Hexane) 0.52; νmax (KBr) 3042, 2986, 1590, 1232, 1025,
967; δH (400 MHz, CDCl3) 1.10 (3H, t, J 7.1 Hz, OCH2CH3),
1.25 (3H, t, J 7.1 Hz, OCH2CH3), 3.85-4.19 (4H, m, OCH2CH3),
5.46 (1H, d, J 26.5 Hz, CH(P)Ar2), 7.32-7.64 (10H, m, Ar-H),
7.74 (2H, d, J 8.0 Hz, Ar-H), 7.86 and 7.89 (2H, d, J 8.0 Hz each,
Ar-H), 8.20 (1H, d, J 8.0 Hz, Ar-H), 8.42 (1H, d, J 8.0 Hz, Ar-
H); δC (101 MHz, CDCl3) 16.3 and 16.5 (d, J 6.1 Hz each), 45.6
(d, J 140.4 Hz), 62.8 (d, J 7.1 Hz), 62.9 (d, J 8.1 Hz), 123.2,
125.6 (d, J 13.1 Hz), 126.5, 127.0, 127.3 (d, J 2.02 Hz), 127.3,
127.6 (d, J 6.1 Hz), 128.2 (d, J 1.0 Hz), 128.8, 129.2, 130.2 (d, J
7.1 Hz), 131.7, 131.9, 132.7 (d, J 2.02 Hz), 134.3, 135.8 (d, J 6.1
Hz), 139.9 (d, J 3.03 Hz), 140.6 (d, J 1.01 Hz); δP (162 MHz,
CDCl3) 25.8; LC/MS: m/z 431 [MH+].
Diethyl
yl)methyl)phosphonate (3j).
((4-bromo-2-methoxyphenyl)(naphthalen-1-
This reaction was performed in a manner similar to the synthesis
of compound 3f using 3-bromoanisole. The compound 3j (73%,
0.574g) was isolated as a mixture of regioisomer 71:29
(colourless liquid); Rf (60% EtOAc/Hexane) 0.55; νmax (KBr)
2980, 1599, 1488, 1026, 964, 779; δH (500MHz, CDCl3) 0.98-
1.03 (4.2H, many lines, OCH2CH3), 1.16 (1.2H, t, J 7.5 Hz,
OCH2CH3), 1.19 (3H, t, J 7.0 Hz, OCH2CH3), 3.73 (3H, s,
OCH3), 3.75-3.81 (1.4H, m, OCH2CH3), 3.86-3.88 (1H, m,
OCH2CH3), 3.89 (1.2H, s, OCH3), 3.91-3.99 (3.2H, m,
OCH2CH3), 5.73 (1H, d, J 26.1 Hz, CH(P)Ar2), 5.80 (0.4H, d, J
26.1 Hz, CH(P)Ar2), 6.80 (1H, dd, J 8.8, 2.7Hz, Ar-H), 6.99-7.00
(0.4H, m, Ar-H), 7.03 (0.4H, dd, J 8.3, 1.8 Hz, Ar-H), 7.12 (1H,
dd, J 2.7, 1.0 Hz, Ar-H), 7.40-7.49 (3H, m, Ar-H), 7.50-7.54
(1.2H, m, Ar-H), 7.60 (1H, dd, J 8.3, 2.4 Hz, Ar-H), 7.74 (0.4H,
d, J 2.5 Hz, Ar-H), 7.76 (1H, d, J 2.0 Hz, Ar-H), 7.78 (0.4H, br,
Diethyl
di(naphthalyl)methyl)phosphonate
(3m).
The
compound 3m was synthesized in a manner analogous to 3k.
This compound (0.549g, 80%) was isolated as a mixture of
regioisomers (50:50, colourless solid); Found: C, 74.44; H, 6.22.
C25H25O3P requires C, 74.24; H, 6.23%]; Rf (50%
EtOAc/Hexane) 0.48; νmax (KBr) 3058, 2982, 1590,1394, 1242,
1041, 961, 781; δH (400 MHz, CDCl3) 1.03-1.21 (12H, m,

7
OCH CH ), 3.71-3.81 (2H, m, OCH CH ), 3.87-4.12 (6H, m,
Procedure for the synthesis of ketones 4a-l
ACCEPTED MANUSCRIPT
2
3
2
3
OCH2CH3) 5.59 (1H, d, J 28.0 Hz, CH(P)Ar2), 6.24 (1H, d, J
28.0 Hz, CH(P)Ar2), 7.43-7.54 (10H, m, Ar-H), 7.60 7.64 (1H,
m, Ar-H), 7.75-7.88 (10H, m, Ar-H), 8.18-8.26 (4H, m, Ar-H),
8.31 (2H, d, J 8.0 Hz, Ar-H), 8.46 (1H, d, J 8.0 Hz, Ar-H); δC
(101MHz, CDCl3) 16.2 and 16.3 (d, J 6.0 Hz each), 16.4 and
16.5 (d, J 6.0 Hz each), 41.0 (d, J 142.4 Hz), 46.1 (d, J 137.4
Hz), 62.7 and 62.8 (d, J 6.0 Hz each), 62.8 and 62.9 (d, J 6.0 Hz
each), 123.2, 123.3, 125.5 (d, J 2.3 Hz), 125.59, 125.63, 125.9 (d,
J 0.6 Hz), 126.1 (d, J 0.6 Hz), 126.5, 126.6, 127.6 (d, J 1.2 Hz),
127.8 (d, J 6.8 Hz), 127.9 (d, J 6.4 Hz), 128.05, 128.07, 128.18
(d, J 1.5 Hz), 128.2 (d, J 1.3 Hz), 128.5 (d, J 6.5 Hz), 128.7 (d, J
8.1 Hz), 129.1, 129.2, 131.8 (d, J 9.8 Hz), 131.9 (d, J 11.5 Hz),
132.5 (d, J 1.9 Hz), 132.7 (d, J 3.2 Hz), 133.1 (d, J 4.3 Hz), 133.4
(d, J 1.9 Hz), 134.1, 134.27, 134.29, 134.36; δP (162MHz,
CDCl3) 25.68 and 26.21; LC/MS: m/z 405 [MH+].
To a stirred solution of phosphonate 3a (0.5gm, 1.411 mmol) in
DMF (2 mL) under oxygen balloon, potassium tert-butoxide
(0.633gm, 5.645 mmol) was added. The reaction mixture was
stirred at room temperature for 1.5 h under oxygen. After
completion of the reaction (monitored by TLC), the mixture was
quenched with water and extracted with EtOAc (3x30 mL). The
combined organic layer was washed with water repeatedly (thrice
using 50 mL water) and then washed with saturated brine
solution and dried over anhydrous Na2SO4. After filtration and
removal of solvent in vacuo, the crude product was purified by
silica gel column chromatography (EtOAc/Hexane 2/98) to
afford the desired compound 4a. All the other compounds 4b-l
were prepared analogously using similar molar quantities of
naphthyl aryl phosphonate and KOtBu.
Naphthalen-1-yl(phenyl)methanone (4a).3d This compound 4a
(0.294g, 90%) was isolated as colourless solid; mp 72-74 C; Rf
Dimethyl di(naphthalyl)methyl)phosphonate (3n). This
compound 3n (0.565g, 80%) was synthesized in a manner
analogous to 3m by starting with 2b (0.500 g, 1.878 mmol) and
was isolated as a mixture of regioisomers (50:50, colourless
solid); [Found: C, 73.22; H, 5.89. C23H21O3P requires C, 73.40;
H, 5.62]; Rf (50% EtOAc/Hexane) 0.45; δH (400MHz, CDCl3)
3.47 (6H, d, J 10.8 Hz, POCH3), 3.60 (6H, two doublets →t, J
10.7 Hz, POCH3), 5.52 (1H, d, J 26.5 Hz, CH(P)Ar2), 6.12 (1H,
d, J 26.4 Hz, CH(P)Ar2)), 7.29-7.51 (10H, m, Ar-H), 7.57-7.61
(1H, m, Ar-H), 7.67-7.69 (1H, m, Ar-H), 7.79-7.89 (9H, m, Ar-
H), 8.09 (1H, s, Ar-H), 8.12-8.16 (3H, m, Ar-H), 8.20 (2H, d, J
8.4 Hz, Ar-H), 8.34 (1H, d, J 7.2 Hz, Ar-H); δC (126 MHz,
CDCl3) 40.8 (d, J 142.1 Hz), 45.7 (d, J 140.6 Hz), 53.4 (d, J 7.2
Hz), 53.6 ( two doublets →t, J 6.7 Hz), 123.03, 123.04, 125.3 (d,
J 2.1 Hz), 125.6 (d, J 2.5 Hz), 125.64, 125.7, 126.1, 126.2, 126.6,
126.8, 127.5 (d, J 4.4 Hz), 127.6 (d, J 3.15 Hz), 127.8 (d, J 6.4
Hz), 128.1, 128.2 (d, J 2.1 Hz), 128.3 (d, J 1.3 Hz), 128.4 (d, J
1.3 Hz), 128.5 (d, J 6.4 Hz), 128.6 (d, J 8.2 Hz), 129.1, 129.2,
131.6 (d, J 9.7 Hz), 131.7 (d, J 11.7 Hz), 132.2 (d, J 2.9 Hz),
132.5 (d, J 1.8 Hz), 132.6 (d, J 4.4 Hz), 133.4 (d, J 2.3 Hz), 133.8
(d, J 6.6 Hz), 134.1, 134.3; δP (162MHz, CDCl3) 28.3 and 28.0;
LC/MS: m/z 377 [MH+].
o
(4% EtOAc/Hexane) 0.52; νmax (KBr) 1658, 1501, 1284, 914,
793; δH (400 MHz, CDCl3) δ 7.47-7.65 (7H, m, Ar-H), 7.89-7.91
(2H, m, Ar-H), 7.95-7.97 (1H, m, Ar-H), 8.04 (1H, d, J 8.0 Hz,
Ar-H), 8.13 (1H, d, J 8.0 Hz, Ar-H); δC (101 MHz, CDCl3) 124.4,
125.7, 126.5, 127.2, 127.8, 128.4, 128.5, 130.4, 131.0, 131.3,
133.3, 133.7, 136.4, 138.3, 198.0; LC/MS: m/z 233 [MH+].
Naphthalen-1-yl(p-tolyl)methanone (4b).13a This compound 4b
o
(0.300g, 90%) was isolated as colourless solid; mp 66-68 C; Rf
(4% EtOAc/Hexane) 0.54; νmax (KBr) 1644, 1601, 1408, 778; δH
(400 MHz, CDCl3) 2.42 (3H, s, CH3-Ar), 7.24-7.26 (2H, m, Ar-
H), 7.46-7.57 (4H, m, Ar-H), 7.75-7.78 (m, 2H, Ar-H), 7.93-
7.90-7.92 (m, 1H, Ar-H), 7.98-7.99 (m, 1H, Ar-H), 8.03-8.05 (m,
1H, Ar-H); δC (101 MHz, CDCl3) 21.7, 124.3, 125.7, 126.3,
127.1, 127.3, 128.3, 129.1, 130.5, 130.9, 133.7, 135.7, 136.8,
144.1, 197.7; LC/MS: m/z 247 [MH+]. The NMR data is very
much consistent with the literature report.13a
(3,4-dimethylphenyl)(naphthalen-1-yl)methanone (4c).13b This
compound (0.289g, 85%) was isolated as colourless solid; mp
o
93-95 C; Rf (3% EtOAc/Hexane) 0.51; νmax (KBr) 1646, 1451,
1021, 951, 777; δH (400 MHz, CDCl3) 2.33 and 2.37 (3H each, s,
CH3-Ar), 7.23 (1H, d, J 8.0 Hz, Ar-H), 7.54-7.60 (5H, m, Ar-H),
7.74 (1H, s, Ar-H), 7.95 (1H, d, J 8.0 Hz, Ar-H), 8.02 (1H, d, J
7.6 Hz, Ar-H), 8.08 (1H, d, J 8.1 Hz, Ar-H); δC (101 MHz,
CDCl3) 19.7, 20.1, 124.4, 125.8, 126.4, 127.1, 127.3, 128.4,
128.5, 129.7, 130.9, 131.0, 131.3, 133.7, 136.1, 136.9, 136.9,
143.0, 198.0; LC/MS: m/z 261 [MH+].
Dimethyl
yl)methyl)phosphonate (3o).
((4,6-dihydropyren-1-yl)(naphthalen-1-
This compound 3o (0.577g, 70%) was synthesized in a manner
analogous to 3f-i and was isolated as a pale yellow solid); mp
o
102-104 C; [Found: C, 77.45; H, 5.21. C29H23O3P requires C,
77.32; H, 5.15]; Rf (40% EtOAc/Hexane) 0.56; νmax (KBr) 3432,
2947, 1729, 1592, 1455, 1244, 1029, 777; δH (500 MHz, CDCl3)
3.35 (3H, d, J 10.7 Hz, POCH3), 3.63 (3H, d, J 10.8 Hz, POCH3),
6.46 (1H, d, J 26.5 Hz, CH(P)Ar2), 7.38-7.44 (2H, m, Ar-H),
7.56-7.59 (1H, m, Ar-H), 7.83-7.87 (2H, m, Ar-H), 8.01-8.08
(3H, m, Ar-H), 8.12-8.15 (2H, m, Ar-H), 8.20-8.25 (3H, m, Ar-
H), 8.39-8.40 (1H, m, Ar-H), 8.44-8.47 (1H, m, Ar-H), 8.62 (1H,
d, J 9.4 Hz, Ar-H); δC (126 MHz, CDCl3) 41.6 (d, J 142.1 Hz),
53.3 and 53.5 (two doublets, J 7.1 Hz each), 122.5, 123.1, 124.8,
125.1, 125.5, 125.52, 125.6, 126.0, 126.7, 127.4 (d, J 0.9 Hz),
127.5 (d, J 1.2 Hz), 128.1 (d, J 5.5 Hz), 128.23, 128.24, 128.5,
128.8 (d, J 9.3 Hz), 129.11, 130.2 (d, J 5.7 Hz), 130.6, 130.62,
130.63, 131.4, 131.8 (d, J 11.4 Hz), 133.16, 133.19, 134.2; δP
(202 MHz, CDCl3) 28.2(s); LC/MS m/z 451 [MH+].
Mesityl(naphthalen-1-yl)methanone (4d)2c In this case, 6 equiv
of KOtBu was used for completion of reaction within 3 h. This
compound (0.138g, 40%) was isolated as colourless solid; mp
o
142-144 C (recrystallized from EtOAc/Hexane~ 1:6); Rf (4%
EtOAc/Hexane) 0.48; νmax (KBr) 3444, 1648, 1610, 1506, 1240,
1047; δH (400MHz, CDCl3) 2.16 (6H, s, CH3-Ar), 2.37 (3H, s,
CH3-Ar), 6.94 (2H, s, Ar-H), 7.28-7.43 (1H, m, Ar-H), 7.62-7.75
(3H, m, Ar-H), 7.95 (1H, d, J 8.0 Hz, Ar-H), 8.05 (1H, d, J 8.1
Hz, Ar-H), 9.25 (1H, d, J 8.5 Hz, Ar-H); δC (126 MHz, CDCl3)
19.5, 21.2, 124.6, 126.2, 126.6, 128.5, 128.7, 130.7, 132.3, 134.1,
134.4, 134.7, 138.7, 202.8; LC/MS: m/z 275 [MH+].

8
Tetrahedron
ACCEPTED MANUSCRIPT
(4-methoxyphenyl)(naphthalen-1-yl)methanone (4e).3f The
7.57 (3H, m, Ar-H), 7.76 (2H, ddd, J 8.1 Hz, 6.0 Hz, 1.0 Hz, Ar-
compound 4e (0.153 g, 45%) is synthesized in a manner
analogous to compound 3a by starting with 2h (0.5g, 1.300
mmol) and is isolated as colourless liquid; Rf (5%
EtOAc/Hexane) 0.49; νmax (KBr) 3053, 2928, 1652, 1506, 1254,
1026; δH (400 MHz, CDCl3) 3.86 (3H, s, OCH3), 6.94 (2H, d, J
8.8 Hz, Ar-H), 7.47-7.58 (4H, m, Ar-H), 7.88 (2H, d, J 8.8 Hz,
Ar-H), 7.93 (1H, d, J 7.8 Hz, Ar-H), 7.99 (1H, d, J 8.0 Hz, Ar-
H), 8.05 (1H, d, J 8.2 Hz, Ar-H); δC (101 MHz, CDCl3) 55.5,
113.7, 124.4, 125.7, 126.3, 126.8, 127.0, 128.4, 130.6, 130.9,
131.1, 132.7, 133.7, 137.0, 163.8, 196.6; LC/MS: m/z 263
[MH+].
H), 7.92-7.95 (1H, m, Ar-H), 8.03 (1H, d, J 8.3 Hz, Ar-H), 8.19-
8.20 (1H, m, Ar-H); The other peaks are observed for other
isomer. δC (101MHz, CDCl3) 124.3, 125.5, 126.5, 127.1, 127.3,
128.1, 128.4, 130.5, 131.3, 133.7, 135.1, 135.7, 136.2, 145.3,
189.7; LC/MS: m/z 239 [MH+].
[1,1'-biphenyl]-4-yl(naphthalen-1-yl)methanone
(4j)16a
Compound 4j (0.322g, 90%) was isolated as colourless solid; Rf
(3% EtOAc/Hexane) 0.60; νmax (KBr) 2924, 1656, 1599, 1289,
1248, 781; δH (400 MHz, CDCl3) 7.41-7.57 (6H, m, Ar-H), 7.62-
7.70 (5H, m, Ar-H), 7.93-7.96 (3H, m, Ar-H), 8.03 (1H, d, J 8.4
Hz, Ar-H), 8.02 (1H, d, J 7.6 Hz, Ar-H); δC (101 MHz, CDCl3)
124.3, 125.6, 126.4, 127.0, 127.2, 127.2, 127.5, 128.2, 128.3,
128.9, 130.8, 130.9, 131.1, 133.6, 136.4, 136.9, 139.8, 145.9,
198.0; LC/MS: m/z 309 [MH+].
(5-iodo-2-methoxyphenyl)(naphthalen-1-yl)methanone (4f)14a
This compound 4f (0.190 g, 50%) was isolated as a mixture of
regioisomers (68:32, colourless liquid); Rf (4% EtOAc/Hexane)
0.60; νmax (KBr) 3051, 2927, 1654, 1480, 1253, 1019; δH (400
MHz, CDCl3) 3.57 (3H, s, OCH3), 6.75 (1H, d, J 8.8 Hz, Ar-H),
7.60-7.62 (5H, m, Ar-H), 7.81 (1H, s, Ar-H), 7.93-8.01 (2H, m,
Ar-H), 8.69-8.71 (1H, d, J 8.4 Hz, Ar-H); the other peaks are
observed due to the presence of other isomer. δC (101 MHz,
CDCl3) 55.6, 82.4, 109.9, 114.3, 125.5, 125.8, 126.5, 127.2,
127.9, 130.7, 131.1, 132.7, 132.9, 133.8, 135.7, 138.6, 141.7,
196.0; Other peaks due to the isomer were also observed in the
spectra. LC/MS: m/z 389 [MH+].
Di(naphthalen-1-yl)methanone (4k)17 The compound 4k
(0.279g, 80%) was isolated as a mixture of isomer (50:50,
brownish solid); Rf (3% EtOAc/Hexane) 0.55; νmax (KBr) 1650,
1504, 1483, 1243, 916, 781; δH (400MHz, CDCl3) 7.53 (2H, t, J
5.2Hz, Ar-H), 7.58-7.69 (13H, m, Ar-H), 7.87 (1H, d, J 9.6Hz,
Ar-H), 7.93 (1H, d, J 6.8Hz, Ar-H), 7.96-8.15 (9H, m, Ar-H),
8.28 (1H, s, Ar-H), 8.59-8.61 (2H, m, Ar-H); δC (126MHz,
CDCl3) 124.3, 124.4. 125.4. 125.7, 125.9, 126.5, 126.57, 126.8,
127.3, 127.7, 127.8, 127.88, 128.4, 128.47, 128.5, 128.6, 129.6,
130.4, 131.1, 131.2, 131.24, 132.4, 132.5, 132.9, 133.8, 133.9,
135.7, 135.73, 136.6, 137.2, 198.0, 199.7; LC/MS: m/z 283
[MH+]. From the isomeric mixture of 4k, a pure isomer (4k’,
0.09 g) was crystallized out from the eluent (Hexane/EtOAc
98/2).
(5-fluoro-2-methoxyphenyl)(naphthalen-1-yl)methanone
(4g)14c This compound 4g (0.138 g, 92%) was isolated as a
colourless solid; mp 72-74 oC; [Found: C, 77.13; H, 4.68.
C18H13FO2 requires C, 77.23; H, 4.61]; Rf (5% EtOAc/Hexane)
0.77; νmax (KBr) 2930, 1653, 1490, 1267, 1020, 726; δH (400
MHz, CDCl3) 3.55 (3H, s, OCH3), 6.89-6.93 (1H, m, Ar-H),
7.17-7.21 (1H, m, Ar-H), 7.30 (dd, J 8.27 Hz, 3.2 Hz, Ar-H),
7.43-7.47 (1H, m, Ar-H), 7.55-7.64 (3H, m, Ar-H), 7.92 (1H, d, J
7.9 Hz, Ar-H), 8.01 (1H, d, J 8.2 Hz, Ar-H), 8.70 (1H, d, J 8.4
Hz, Ar-H); δC (101 MHz, CDCl3) 56.3, 113.3 (d, J 7.6 Hz), 117.0
(d, J 24.1 Hz), 118.9 (d, J 23.1 Hz), 124.3, 125.8, 126.4, 127.9,
128.5. 130.3, 130.7, 131.07 (d, J 5.9 Hz), 132.8, 133.8, 135.9,
154.4 (d, J 2.1 Hz), 156.7 (d, J 240.9 Hz), 196.5 (d, J 1.3Hz);
LC/MS m/z 281 [MH+].
Naphthalene-1-yl(naphthalene-2-yl)methanone (4kʹ).17c Rf
(3% EtOAc/Hexane) 0.53; νmax (KBr) 1650, 1504, 1243, 781; δH
(400 MHz, CDCl3) 7.51-7.62 (6H, m, Ar-H), 7.86 (1H, d, J 8.0
Hz, Ar-H), 7.92-7.99 (3H, m, Ar-H), 8.06-8.16 (3H, m, Ar-H),
8.28 (1H, s, Ar-H); δC (101 MHz, CDCl3) 124.4, 125.4, 126.5,
126.8, 127.3, 127.7, 127.8, 128.4, 128.7, 129.7, 131.0, 131.2,
132.3, 132.9, 133.7, 135.6, 135.7, 136.6, 198.0; LC/MS: m/z 283
[MH+].
(4-Bromo-2-methoxyphenyl)(naphthalen-1-yl)methanone
(4h)14b
(naphthalen-1-yl(pyren-1-yl))methanone (4l)19
The compound 4h (0.220g, 60%) was isolated as a mixture of
regioisomers (71:29, colorless liquid); Rf (3% EtOAc/Hexane)
0.54; νmax (KBr) 2924, 1659, 1590, 1483, 1246, 916, 781; δH
(500MHz, CDCl3), (regioisomers 69:31) 3.89 (3H, s, OCH3),
3.62 (1.4H, s, OCH3), 6.92(1H, dd, J 8.6, 2.5Hz, Ar-H), 7.14-
7.15 (0.4H, m, Ar-H), 7.21-7.23 (1.4H, m, Ar-H), 7.42-7.48
(2.9H, m, Ar-H), 7.55-7.65 (4.4H, m, Ar-H), 7.91-7.94 (1.4H, m,
Ar-H), 8.01 (0.4H, d, J 8.2Hz, Ar-H), 8.04 (1H, d, J 8.2Hz, Ar-
H), 8.59-8.61 (0.4H, m, Ar-H), 8.64-8.66 (1H, m, Ar-H); δC
(126MHz, CDCl3) 55.7, 113.0, 119.2, 124.8, 125.9, 126., 127.7,
127.9, 128.4, 131.6, 131.1, 132.6, 132.9, 133.8, 133.9, 135.4,
161.8, 196.9; other isomer 55.9, 115.6, 122.3, 123.8, 125.8,
126.4, 126.8, 128.3, 128.9, 129.7, 130.7, 131.9, 132.5, 133.8,
133.81, 136.5, 158.8, 196.7; ); LC/MS: m/z 341 [MH+] and 343
[MH+2]+ (1:1).
The compound 4l (0.143g, 90%) was isolated as colourless
solid); mp 80-82oC; [Found: C, 90.82; H, 4.58. C27H16O requires
C, 90.99; H, 4.52]; Rf (5% EtOAc/Hexane) 0.85; νmax (KBr)
1645, 1502, 1240, 922, 779; δH (500 MHz, CDCl3) 7.44-7.47 (1H,
m, Ar-H), 7.61-7.66 (3H, m, Ar-H), 7.69-8.00 (1H, m, Ar-H), 8.06-
8.10 (5H, m, Ar-H), 8.19-8.21 (2H, m, Ar-H), 8.27-8.29 (2H, m, Ar-
H), 8.64-8.66 (1H, m, Ar-H), 8.84 (1H, d, J 8.0 Hz, Ar-H); δC (126
MHz, CDCl3) 123.9, 124.4, 124.5, 124.9, 124.93, 126.0, 126.2,
126.4, 126.5, 126.6 merged with other carbon, 127.2, 127.9, 128.6,
128.9, 129.5, 129.6, 130.4, 130.6, 130.7, 131.1, 132.5, 133.8, 133.9,
137.7, 200.3; LC/MS m/z 357 [MH+].
Acknowledgments
Naphthalen-1-yl(thiophen-2-yl)methanone
(4i).15
The
We thank DST-SERB, India (SB/S1/IC-07A/2013) for financial
support. GP thanks BITS-Pilani-Hyderabad campus for the
fellowship. A DST-FIST grant partly supported this work.
compound 4i (0.138g, 42%) was isolated as a mixture of
regioisomeric (85:15) colourless solid; Rf (4% EtOAc/Hexane)
0.44; νmax (KBr) 1638, 1509, 1409, 1051, 782; δH (500 MHz,
CDCl3) 7.12-7.14 (1H, m, Ar-H), 7.49-7.51 (1H, m, Ar-H), 7.55-

9
2005, 105, 1491; (c) Wang, C.; Dong, H.; Hu, W.; Liu, Y.; Zhu,
D. Chem. Rev. 2012, 112, 2208.
5. References
ACCEPTED MANUSCRIPT
12. The 31P NMR of this reaction mixture (for the reaction of 2a with
anthracene using FeCl3/ DCE at rt) showed multiple peaks in the
range of δ = 25.1 to δ = 26.6 ppm and that could be due to the
formation of several isomeric mixture of products.
13. A very recent report: (a) Skillinghaug, B.; Skoeld, C.; Rydfjord, J.;
Svensson, F.; Behrends, M.; Saevmarker, J.; Sjoeberg, P. J. R.;
Larhed, M. J. Org. chem. 2014, 79, 12018; (b) Based on Scifinder
search, compound 4c is only registered with CAS: 1097063-30-3
and currently available with Novel Chemical Solutions Product
List, United States with the price (495 USD for 1g).
14. (a) As per Scifinder search, compound 4f is registered with CAS:
1094748-91-0 and sporadically available with United States based
companies Aldlab Chemicals Building Blocks and Aurora
Building Blocks. (b) Compound 4g is registered with CAS:
1097056-41-1 and is available with Aldlab Chemicals Building
Blocks, Aurora Building Blocks, Novel Chemical Solutions
Product List, United States with the price (495 USD for 1g). (c)
Compound 4h is registered with CAS: 1548087-45-1 and
available with Aurora Building Blocks, USA.
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