Pd-Catalyzed Isocyanide Assisted Reductive Cyclization of 1-(2-Hydroxyphenyl)-propargyl Alcohols for 2-Alkyl/Benzyl Benzofurans and Their Useful Oxidative Derivatization

Article abstract of DOI:10.1021/acs.joc.5b02204

An unusual Pd-catalyzed isocyanide assisted 5-exo-dig reductive cyclization of 1-(2-hydroxyphenyl)-propargyl alcohols is achieved for 2-alkyl/benzyl benzofurans. The reaction features a high substrate scope, insensitivity to air, and excellent product yielding. Further, a direct metal-free C-H functionalization (azidation, alkoxylation, and hydroxylation) and selective oxidative cleavage of thus synthesized 2-benzylfurans are described for azido-, alkoxy-, hydroxyl-, amide-, and tetrazolyl adducts.

Full text of DOI:10.1021/acs.joc.5b02204

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Article
Pd-Catalysed Isocyanide Assisted Reductive Cyclization
of 1-(2-Hydroxyphenyl)-Propargyl Alcohols for 2-Alkyl/
Benzyl Benzofurans and their Useful Oxidative Derivatization
Rajesh Manda, Nuligonda Thirupathi, Thota Jagadeshwar Reddy, Sanjeev Kanojiya, and Maddi Sridhar Reddy
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b02204 • Publication Date (Web): 24 Nov 2015
Downloaded from http://pubs.acs.org on November 24, 2015
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Pd-Catalysed Isocyanide Assisted Reductive Cyclization of 1-(2-Hydroxyphenyl)-
Propargyl Alcohols for 2-Alkyl/Benzyl Benzofurans and their Useful Oxidative
Derivatization
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Manda Rajesh,a Nuligonda Thirupathi,a Thota Jagadeshwar Reddy,b Sanjeev Kanojiya b and
Maddi Sridhar Reddya,c*
aMedicinal & Process Chemistry Division, CSIRꢀCentral Drug Research Institute, BSꢀ10/1,
Sector 10, Jankipuram extension, Sitapur Road, Lucknow 226031, India. bSAIF Division,
CSIRꢀCDRI, Lucknow 226031, India. cAcademy of Scientific and Innovative Research, New
Delhi 110001, India. Email: msreddy@cdri.res.in
ABSTRACT: An unusual Pdꢀcatalyzed isocyanide assisted 5ꢀexoꢀdig reductive cyclization
of 1ꢀ(2ꢀhydroxyphenyl)ꢀpropargyl alcohols is achieved for 2ꢀalkyl/benzyl benzofurans. The
reaction features a high substrate scope, insensitivity to air and excellent product yielding.
Further, a direct metal free CꢀH functionalization (azidation, alkoxylation and hydroxylation)
and selective oxidative cleavage of thus synthesized 2ꢀbenzylfurans is described for azidoꢀ,
alkoxyꢀ, hydroxylꢀ, amideꢀ and tetrazolyl adducts.
INTRODUCTION
Electrophilic cyclization of alkynes with nucleophile tether is an increasingly versatile
strategy for the synthesis of large variety of heteroꢀ and carbocycles.1 Among structurally
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diverse substrates used in the strategy, the propargyl alcohols or their derivatives with
nucleophile tether are very frequently used precursors which offer interesting postꢀcyclization
transformations viz. elimination, migration, oxidation, etc.1 On the other hand, the concept of
isocyanide insertion between carbonꢀpalladium bond has paved a useful pathway for the
construction of variety of otherwise difficult CꢀC bonds.2 As part of our onꢀgoing program of
uncovering the new activities of activated alkynes,3 we recently reported a tandem oxyꢀ
palladation/isocyanide insertion strategy for the conversion of hydroxyphenyl terminal
propargyl alcohols to benzofuranyl acetamides (Scheme 1).3c Subsequently, we discovered a
rare isocyanide assisted reductive cyclization of hydroxyphenyl internal propargyl alcohols to
2ꢀalkyl/benzyl benzofurans,4 the privileged scaffolds found in numerous biologically and
medicinally active molecules.5 Unlike in most cases reported,3 we found the insertion of
isocyanide between oxygenꢀpalladium bond in preference to carbonꢀpalladium perhaps due to
Scheme 1. Benzofurans via cyclization of hydroxyphenyl propargyl alcohols.
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steric constraints. The 2ꢀalkyl/benzylꢀ3ꢀunsubstituted benzofurans we synthesized here are
identified as excellent precursors for diverse selective functionalizations at both benzylic and
Cꢀ3 positions via selective metal free CꢀH activations and benzofuranyl methylꢀphenyl bond
cleavage.
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RESULTS AND DISCUSSION
We initiated our studies with the optimization of the conversion of 1aa to 2aa as shown in
Table 1. A screen of several Pd(II)ꢀcatalysts along with Na2CO3 as base in acetonitrile
revealed that Pd(OAc)2 as the best choice. However, no reaction occurred in the absence of
Pdꢀcatalyst. Change of base to Cs2CO3 cleanly furnished the product in 85% yield. Organic
bases like TEA, DIPEA and DBU were found to be poor promoters. Solvents other than
acetonitrile were not suitable for the transformation.
Table 1. Optimization studies.a
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Although it was evident that there was no any reducing agent, which was essential for the
reduction part of the reaction, other than isocyanide was used, a control experiment excluding
tꢀBuNC was conducted to get insight in to the mechanism. The experiment yielded the simple
5ꢀexoꢀdig cyclization product 34f demonstrating that the isocyanide was necessary for
reductive elimination of allylic hydroxyl group (Scheme 2). However, when 3 was subjected
to the standard conditions, no reaction occurred but a slow decomposition. This indicates that
the intermediate A with CꢀPd bond intact was necessary to further proceed to the product via
formation of oxapallada cycle B by the isocycanide insertion between palladium and oxygen.
B then probably expelled tꢀBuNCO followed by PdX2 to furnish final product 2aa via C and
D though addition elimination processes.
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Scheme 2. Mechanistic evaluation.
With optimal reaction conditions in hand, we studied the scope of the tandem
cyclization/reductive elimination of a variety of salicylaldehyde derived propargyl alcohols
(Table 2). Substrates bearing alkyl groups (methyl or tꢀbutyl) showed similar reactivity to 1aa
to produce 2ab-ad in excellent yields (79ꢀ87%). Halo groups were found to be well
compatible with the reaction as in case of the synthesis of 2af-aj where mono halo precursors
showed better reactivity than their dihalo counterparts. Irrespective of the position of alkoxy
group (orthoꢀ, metaꢀ or paraꢀ), all the electron rich substrates 1ak-am showed uniformly the
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excellent reactivity (2ak-am in 83ꢀ90% yields). In case of substrate 1an, the product was
obtained with the concomitant transformation of unprotected hydroxyl group to carbamate
(2an). This resulted via the phenoxyl addition to the isocyanate, the oxidized byproduct of
isocyanide. This stands as a proof for the isocyanide assisted reductive elimination of the
propargylic hydroxyl group. Next, electron deficient substrate 1ao showed moderate
reactivity to produce 2ao in 59% yield. Finally, cyclization/reductive elimination cascade of
substrates 1ap-au, possessing arylꢀsubstitution/fusion, occurred uneventfully affording
products 2ap-au in good to excellent yields.
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Table 2. Reductive cyclization of hydroxyphenyl propargyl alcohols 1aa-au.a
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Next, substrate scope with respect to substitution on alkyne terminal was studied (Table 3).
Aryl acetylene based substrates were initially screened. Thus, alkyl substituted aryl adducts
2ba-da were obtained in excellent yields (83ꢀ86%). Electron rich precursors (1ea-ga) were
relatively highly productive compared to halogenated substrates (1ha-ia). 2ꢀthiophenyl
substrate 1ja also furnished the corresponding product 2ja in 82% yield. Interestingly, alkyl
acetylene based propargyl alcohols (1ka-oa) were found to be equally reactive (75ꢀ85%) in
the cyclization/reductive elimination sequence.
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Setting a limitation, the reaction was not applicable for 3oꢀpropargyl alcohols (for the
synthesis of 2,3ꢀdisubstituted benzofurans), perhaps due to steric hinderance from the both
terminals of the reactive centre. Also, all the efforts to expand the reaction scope for the
synthesis of indoleꢀ and benzothiopheneꢀderivatives were failed to yield the desired products.
Table 3. Reductive cyclization of hydroxyphenyl propargyl alcohols 1ba-oa.a
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We next aimed at the derivatization of the 2ꢀalkylbenzofurans as they seemed interesting with
a nucleophilic C3 center and a benzylic system as radical/carbocation base. We first targeted
the oxidative functionalization of benzylic position of 2. We envisioned that DDQ can
oxidize benzofuranyl benzylic position, and the resultant radical species/carbocation can be
trapped by various nucleophiles. Thus, 2aa was treated with 2 equivalents of DDQ in AcOH
with TMSN3 as azide source (nucleophile) to trap the incipient electrophile. As expected,
azide adduct 4a was cleanly obtained in 86% yield (Table 4). After thorough literature search,
we found that there is no such precedent for direct metal free CꢀH azidation in the literature.
Interestingly, even in case of metal catalysed direct CꢀH azidation, there are only two reports
which appeared most recently, one of which was specific for tertiary C(sp3)ꢀH azidation via
iodosobenzene assisted Fe(II)ꢀcatalysis6a and the other was nonꢀspecific with tertiary C(sp3)ꢀ
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Table 4. Metal free selective C(sp3)-H azidation of 2.a
H and benzylic CꢀH azidation via Mn(II)ꢀcatalysis.6b Having observed the dearth of literature
on this useful transformation, we wanted to verify the generality of our new finding of DDQ
assisted direct CꢀH azidation of 2ꢀbenzyl benzofurans. Pleasingly, various benzyl
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benzofurans, irrespective of electronic nature of both benzylꢀ and benzofuran groups, could
be directly azidated in good to excellent yields (75ꢀ86%).
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We next turned to extend the method for direct C(sp3)ꢀH alkoxylation by substituting
trapping agent TMSN3 by an alcohol. When treated the 2aa with 2 equivalents of DDQ in
CH2Cl2/MeOH (1:1), the desired methoxy adduct 5a was cleanly obtained in 70% yield
(Table 5). Such a DDQ mediated alkoxylation was earlier reported by Bao et al7 but it was
specifically on aryl allyl benzenes. Surprisingly, there is no direct alkoxylation of
diarylmethanes is pursued in the literature although a very few donating group assisted metal
catalyzed methods are reported.8 Hence, we decided to verify the generality of this direct
alkoxylation of benzylbenzofurans. Similar to MeOH, other nꢀalknols like EtOH, nꢀPrOH and
nꢀBuOH reacted smoothly (5b-d in 71ꢀ74%) whereas hindered alcohols iꢀPrOH and tꢀBuOH
showed no reactivity. Notably, less nucleophilic phenol also smoothly reacted to give 5e in
59% yield. Finally, propargyl alcohol was successfully used in this oxidative coupling to
obtain 5f in 61%.
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Table 5. Oxidative dehydrogenative coupling of alcohols with 2aa.a
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Further, we treated 2aa with Ac2O/AcOH (1:1) to get acetoxy derivative in line with above
oxidative couplings. But, it revealed the hydrolysed (deacylated) adduct 6 in 71% yield
(Scheme 3). When treated with DDQ in AcOH in the absence of any trapping nucleophile,
2aa underwent an oxidative dehydrogenative dimerization to afford 7 in 82% yield. It appears
that electron rich Cꢀ3 of 2aa acted as trapping nucleophile in the forcible conditions. When
subjected to 3 equiv of MnO2 in refluxing DCE, 2aa produced the benzoyl benzofuran in
74% yield. Moving on to selective functionalization of Cꢀ3 of 2, we treated 2aa with NBS in
refluxing CCl4. 3ꢀBromo adduct 9 was isolated as a sole product in 68% yield.
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Scheme 3. Selective oxidative functionalizations of 2.
Finally, we attempted to uncover any difference in migratory aptitudes between phenyl and
αꢀbenzofuranyl groups of 2 in tandem oxidative cleavage/migration for the synthesis of
tetrazole and amide adducts under known conditions.9 The reports were only on symmetrical
diaryl methanes, perhaps the unsymmetrical substrates were thought to yield mixture of
adducts because of similar migratory aptitudes of both aryl groups. Pleasingly, when
subjected to Cu(I)ꢀcatalyzed azidationꢀmigrationꢀtriazolation cascade,9a 2aa and 2ea gave the
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single regioisomers in 83% and 55% yields respectively, indicating that αꢀbenzofuranyl
group has relatively highly less migratory aptitude (Scheme 4). Similarly, Fe(II)ꢀcatalyzed
DDQꢀmediated amidative cleavage9b of 2ea and 2ga led to Nꢀaryl benzofuranamides 11b-c
with complete selectivity whereas 2aa underwent a mere oxidation probably via competitive
hydrolysis of the imine intermediate.
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Scheme 4. Derivatization of 2 via selective oxidative cleavages.
CONCLUSION
In summary, we demonstrated an efficient conversion of 1ꢀ(2ꢀhydroxyphenyl) propargyl
alcohols to 2ꢀalkyl/benzyl benzofurans via Pdꢀcatalyzed 5ꢀexoꢀdig cyclization followed by a
rare isocyanide assisted reductive elimination of allyl alcohol. The reaction, while providing a
high substrate scope, neither required an inert atmosphere nor needed an elevated
temperature. Further, a variety of useful transformations of the products is achieved via
unassisted/direct CꢀH azidation/hydroxylation/alkoxylation and selective oxidatative cleavage
of benzofuranylmethylꢀphenyl bond.
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EXPERIMENTAL SECTION
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General Information: All reagents and solvents were purchased from commercial sources
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and used without purification. NMR spectra were recorded with a 400 or 500 MHz
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spectrometer for 1H NMR, 50, 100 or 125 MHz for C NMR spectroscopy. Chemical shifts
are reported relative to the residual signals of tetramethylsilane in CDCl3 or deuterated
solvent CDCl3 for H and 13C NMR spectroscopy. Multiplicities are reported as follows:
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singlet (s), doublet (d), doublet of doublets (dd), doublet of triplets (dt), triplet (t), quartet (q),
multiplet (m). HRMS were recorded by using DART and Orbitrap mass spectrometers.
Column chromatography was performed with silica gel (100–200 mesh) as the stationary
phase. All reactions were monitored by using TLC. The purity and characterization of
compounds were further established by using HRMS.
Starting materials 1 were prepared in one step following the literature procedures.10
General Procedure A for the Synthesis of 2-benzyl benzofurans (2aa-2oa) from 2-(1-
hydroxy-3-phenylprop-2-yn-1-yl) phenols (1aa-1oa) taking Synthesis of 2aa as an
example: To a stirred solution of 2ꢀ(1ꢀhydroxyꢀ3ꢀphenylpropꢀ2ꢀynꢀ1ꢀyl) phenol 1aa (224
mg, 1 mmol, 1 eq) in 4 mL of CH3CN was added Pd(OAc)2 (11.20 mg, 0.05 mmol, 0.05 eq),
Cs2CO3 (390 mg, 1.2 mmol, 1.2 eq), tertꢀbutyl isocyanide (99.6 mg, 1.2 mmol, 1.2 eq) at
room temperature. The reaction mixture was stirred at room temperature until complete
conversion of starting material monitored by TLC (4h for 2aa-2ae, 2ak-2am, 12h for 2af,
2ag, 2ao, 2ha-2ia, 6h for 2ba-2ga, 2ja, 10h for 2ap-2au, 2an, 15h for 2ka-2oa, 18h for 2ah-
2aj). The reaction mixture was diluted with water (20ml) and extracted with EtOAc
(2x20ml). The combined extracts were washed with brine (15 mL) and dried over Na2SO4.
After removal of the solvent under reduced pressure the crude material was purified on silica
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using hexane (2%ꢀ5% EtoAc/hexanes for 2ak-2am, 2ap-2au, 2an, 2ba-2ga) to get 2aa (179
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mg, 86 %) as yellow oil.
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2-benzylbenzofuran11a (2aa): yellow oil; Rf = 0.80 (SiO2, Hexane); H NMR (400 MHz,
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CDCl3) δ 7.41ꢀ7.34 (m, 2H), 7.34ꢀ7.24 (m, 4H), 7.24ꢀ7.14 (m, 3H), 6.37 (d, J = 0.8 Hz, 1H),
4.11 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 157.9, 155.1, 137.3, 129.0, 128.9, 128.7, 126.8,
123.5, 122.6, 120.5, 111.0, 103.4, 35.0.
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2-benzyl-6-methylbenzofuran (2ab): 2ab (0.190 g) was obtained from 1ab (0.238 g, 1
mmol) following general procedure A. Yield 85 %; colorless oil; Rf = 0.76 (SiO2, Hexane);
1H NMR (400 MHz, CDCl3) δ 7.35ꢀ7.28 (m, 5H), 7.27ꢀ7.24 (m, 1H), 7.21 (d, J = 0.5 Hz,
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1H), 7.03ꢀ6.97 (m, 1H), 6.32 (d, J = 0.9 Hz, 1H), 4.09 (s, 2H), 2.44 (s, 3H); C NMR (100
MHz, CDCl3) δ 157.2, 155.5, 137.5, 133.6, 129.0, 128.7, 126.8, 126.3, 123.9, 120.0, 111.3,
103.3, 35.1, 21.7; IR (neat) ν 2924, 1405, 1384, 1155, 668 cmꢀ1; HRMS (DARTꢀTOF) calcd
for C16H15O[M + H]+ 223.1123, found 223.1129.
2-benzyl-7-methylbenzofuran (2ac): 2ac (0.194 g) was obtained from 1ac (0.238 g, 1
mmol) following general procedure A. Yield 87 %; colorless oil; Rf = 0.76 (SiO2, Hexane);
1H NMR (400 MHz, CDCl3) δ 7.40ꢀ7.28 (m, 6H), 7.12 (t, J = 7.5 Hz, 1H), 7.06 (d, J = 7.2
Hz, 1H), 6.37 (s, 1H), 4.16 (s, 2H), 2.54 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.6, 154.1,
137.5, 129.0, 128.6, 124.5, 122.6, 121.2, 117.9, 103.7, 35.1, 15.1; IR (neat) ν 3019, 1495,
1384, 1158, 954, 700 cmꢀ1; HRMS (DARTꢀTOF) calcd for C16H15O[M + H]+ 223.1123,
found 223.1131.
2-benzyl-7-(tert-butyl)benzofuran (2ad): 2ad (0.209 g) was obtained from 1ad (0.280 g, 1
mmol) following general procedure A. Yield 79 %; Light yellow oil; Rf = 0.64 (SiO2,
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Hexane); H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 1.7 Hz, 1H), 7.41ꢀ7.36 (m, 2H), 7.36ꢀ
7.27 (m, 5H), 6.41 (d, J = 0.9 Hz, 1H), 4.14 (s, 2H), 1.42 (s, 9H);13C NMR (100 MHz,
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CDCl3) δ 157.9, 153.3, 145.6, 137.5, 128.9, 128.6,128.6, 126.8, 121.3, 116.8, 110.3, 103.6,
35.1, 34.7, 32.0; IR (neat) ν 3019, 1495, 1384, 1158, 954, 699 cmꢀ1; HRMS (DARTꢀTOF)
calcd for C19H21O[M + H]+ 265.1592, found 265.1603.
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2-benzyl-5,7-di-tert-butylbenzofuran (2ae): 2ae (0.253 g) was obtained from 1ae (0.336 g,
1 mmol) following general procedure A. Yield 79 %; colorless oil; Rf = 0.61 (SiO2, Hexane);
1H NMR (400 MHz, CDCl3) δ 7.35ꢀ7.27 (m, 5H), 7.27ꢀ7.20 (m, 1H), 7.18 (d, J = 1.9 Hz,
13
1H), 6.30 (s, 1H), 4.11 (s, 2H), 1.47 (s, 9H), 1.35 (s, 9H); C NMR (100 MHz, CDCl3) δ
156.9, 151.4, 145.3, 137.8, 133.6, 129.0, 128.6, 126.6, 118.1, 114.6, 103.2, 35.2, 34.9, 34.5,
32.0, 30.0; IR (neat) ν 2957, 1638, 1385, 1155, 1068, 668 cmꢀ1; HRMS (DARTꢀTOF) calcd
for C23H29O[M + H]+ 321.2218, found 321.2230.
2-benzyl-5-chlorobenzofuran11a (2af): 2af (0.175 g) was obtained from 1af (0.258 g, 1
mmol) following general procedure A. Yield 72 %; yellow oil; Rf = 0.82 (SiO2, Hexane); 1H
NMR (400 MHz, CDCl3) δ 7.42 (d, J = 2.0 Hz, 1H), 7.37ꢀ7.27 (m, 6H), 7.16 (dd, J = 8.7, 2.1
Hz, 1H), 6.32 (d, J = 0.5 Hz, 1H), 4.09 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 159.6, 153.5,
136.9, 130.3, 129.0, 128.8, 128.2, 127.0, 123.7, 120.1, 111.9, 103.1, 35.1.
2-benzyl-5-bromobenzofuran11a (2ag): 2ag (0.225 g) was obtained from 1ag (0.302 g, 1
mmol) following general procedure A. Yield 79 %; yellow gum; Rf = 0.82 (SiO2, Hexane);
1H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 1.7 Hz, 1H), 7.37ꢀ7.27 (m, 7H), 6.32 (d, J = 0.8
Hz, 1H), 4.09 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 159.4, 153.8, 136.9, 130.9, 129.0,
128.8, 127.0, 126.4, 123.2, 115.7, 112.4, 103.0, 35.0.
2-benzyl-5,7-dichlorobenzofuran (2ah): 2ah (0.174 g) was obtained from 1ah (0.292 g, 1
1
mmol) following general procedure A. Yield 63 %; yellow oil; Rf = 0.83 (SiO2, Hexane); H
NMR (500 MHz, CDCl3) δ 7.29ꢀ7.27 (m, 1H), 7.25ꢀ7.17 (m, 5H), 7.14 (d, J = 1.9 Hz, 1H),
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6.22 (s, 1H), 4.05 (s, 2H); C NMR (100 MHz, CDCl3) δ 160.8, 149.5, 136.4, 131.3, 129.1,
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128.9, 128.4, 127.2, 123.7, 118.8, 116.9, 103.8, 35.0; IR (neat) ν 2926, 2400, 1445, 1384,
1156, 848,668 cmꢀ1; HRMS (APCIꢀFTMS) calcd for C15H10Cl2O.+[M].+ 276.0109, found
276.0100.
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2-benzyl-5,7-dibromobenzofuran (2ai): 2ai (0.225 g) was obtained from 1ai (0.380 g, 1
mmol) following general procedure A. Yield 62 %; light yellow oil; Rf = 0.83 (SiO2,
1
Hexane); H NMR (400 MHz, CDCl3) δ 7.50 (dd, J = 2.6, 1.8 Hz, 2H), 7.38ꢀ7.27 (m, 5H),
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6.31 (s, 1H), 4.13 (s, 2H); C NMR (100 MHz, CDCl3) δ 160.6, 151.2, 136.4, 131.5, 129.1,
128.9, 127.2, 122.4, 115.8, 104.4, 103.8, 35.0; IR (neat) ν 3018, 2854, 1496, 1383, 1150, 847,
701, 499 cmꢀ1; HRMS (APCIꢀFTMS) calcd for C15H10Br2O.+[M].+ 363.9093, found
363.9087.
2-benzyl-7-bromo-5-chlorobenzofuran (2aj): 2aj (0.192 g) was obtained from 1aj (0.336 g,
1 mmol) following general procedure A. Yield 60 %; light yellow oil; Rf = 0.83 (SiO2,
Hexane); 1H NMR (500 MHz, CDCl3) δ 7.29ꢀ7.26 (m, 3H), 7.25ꢀ7.17 (m, 4H), 6.23 (s, 1H),
4.05 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 160.8, 150.9, 136.4, 130.9, 129.1, 129.0, 128.9,
128.7, 127.2, 126.3, 119.4, 103.9, 35.0; IR (neat) ν 1622, 1405, 1219, 1155, 771 cmꢀ1;
HRMS (APCIꢀFTMS) calcd for C15H10BrClO.+[M].+ 319.9604, found 319.9598.
2-benzyl-5-methoxybenzofuran11a (2ak): 2ak (0.215 g) was obtained from 1ak (0.254 g, 1
mmol) following general procedure A. Yield 90 %; brown gum; Rf = 0.62 (SiO2, 2%
1
EtOAc/Hexanes); H NMR (400 MHz, CDCl3) δ 7.37ꢀ7.21 (m, 6H), 6.94 (d, J = 2.5 Hz,
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1H), 6.81 (dd, J = 8.8, 2.6 Hz, 1H), 6.31 (d, J = 0.8 Hz, 1H) 4.08 (s, 2H), 3.82 (s, 3H); C
NMR (100 MHz, CDCl3) δ 158.8, 155.9, 150,1, 137.4, 129.5, 129.0, 128.7, 126.8, 111.9,
111.4, 103.6, 103.4, 56.0, 35.2;
2-benzyl-6-methoxybenzofuran11a (2al): 2al (0.198 g) was obtained from 1al (0.254 g, 1
mmol) following general procedure A. Yield 83 %; light brown gum; Rf = 0.62 (SiO2, 2%
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EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.39ꢀ7.25 (m, 6H), 7.00 (d, J = 2.0 Hz, 1H),
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6.85 (dd, J = 8.5, 2.2 Hz, 1H), 6.33 (d, J = 0.9 Hz, 1H), 4.10 (s, 2H), 3.84 (s, 3H); C NMR
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(100 MHz, CDCl3) δ 157.5, 156.8, 156.0, 137.5, 128.9, 128.6, 126.8, 122.1, 120.5, 111.3,
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103.1, 96.0, 55.8, 35.0;
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2-benzyl-7-ethoxybenzofuran (2am): 2am (0.210 g) was obtained from 1am (0.268 g, 1
mmol) following general procedure A. Yield 83 %; light yellow gum; Rf = 0.59 (SiO2, 2%
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EtOAc/Hexane); H NMR (400 MHz, CDCl3) δ 7.39ꢀ7.25 (m, 5H), 7.15ꢀ7.04 (m, 2H), 6.77
(d, J = 7.2 Hz, 1H), 6.32 (s, 1H), 4.28 (q, J = 6.9 Hz, 2H), 4.16 (s, 2H), 1.53 (t, J = 7.0 Hz,
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3H); C NMR (100 MHz, CDCl3) δ 158.2, 144.4, 137.3, 130.7, 129.1, 128.6, 126.8, 123.2,
112.8, 107.1, 103.8, 64.5, 35.0, 15.0; IR (neat) ν 2400, 1385, 1155, 929, 669 cmꢀ1; HRMS
(DARTꢀTOF) calcd for C17H17O2[M + H]+ 253.1229, found 253.1234.
2-benzylbenzofuran-5-yl tert-butylcarbamate (2an): 2an (0.223 g) was obtained from 1an
(0.240 g, 1 mmol) following general procedure A. Yield 69 %; light yellow gum; Rf = 0.46
1
(SiO2, 5% EtOAc/Hexanes); H NMR (400 MHz, CDCl3) δ 7.35ꢀ7.24 (m, 6H), 7.20 (d, J =
2.2 Hz, 1H), 6.94 (dd, J = 8.7, 2.3 Hz, 1H), 6.34 (s, 1H), 4.96 (bs, 1H), 4.09 (s, 2H), 1.39 (s,
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9H); C NMR (100 MHz, CDCl3) δ 159.1, 152.4, 146.5, 137.2, 129.4, 128.9, 128.7, 126.9,
117.6, 113.4, 111.1, 103.8, 50.9, 35.1, 29.8; IR (KBr) ν 2926, 2400, 1740, 1384, 1162, 928
cmꢀ1; HRMS (DARTꢀTOF) calcd for C20H22NO3[M + H]+ 324.1600, found 324.1609.
2-benzyl-5-nitrobenzofuran11a (2ao): 2ao (0.150 g) was obtained from 1ao (0.269 g, 1
mmol) following general procedure A. Yield 59 %; light yellow gum; Rf = 0.52 (SiO2, 5%
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EtOAc/Hexanes); H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 2.2 Hz, 1H), 8.15 (dd, J = 8.9,
2.3 Hz, 1H), 7.46 (d, J = 9.0 Hz, 1H), 7.39ꢀ7.24 (m, 5H), 6.50 (s, 1H), 4.14 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 161.6, 157.9, 144.2, 136.2, 129.3, 129.0, 128.9, 127.3, 119.6, 117.0,
111.3, 104.2, 35.1;
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2-benzyl-5-phenylbenzofuran (2ap): 2ap (0.205 g) was obtained from 1ap (0.300 g, 1
o
mmol) following general procedure A. Yield 72 %; white solid, mp 96ꢀ98 C; Rf = 0.63
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(SiO2, Hexanes); H NMR (400 MHz, CDCl3) δ 7.70(s, 1H), 7.65ꢀ7.60 (m, 2H), 7.50ꢀ7.43
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(m, 4H), 7.40ꢀ7.33 (m, 5H), 7.33ꢀ7.27 (m, 2H), 6.45 (s, 1H), 4.16 (s, 2H); 13C NMR (100
MHz, CDCl3+DMSO) δ 158.6, 154.7, 141.9, 137.2, 136.3, 129.4, 129.0, 128.8, 128.7, 127.5,
126.9, 126.8, 123.2, 119.1, 111.1, 103.7, 35.1; IR (KBr) ν 3019, 1406, 1385, 1155, 1068, 669
cmꢀ1; HRMS (DARTꢀTOF) calcd for C21H17O[M + H]+ 285.1279, found 285.1289.
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2-benzyl-5-(4-chlorophenyl)benzofuran (2aq): 2aq (0.224 g) was obtained from 1aq (0.334
o
g, 1 mmol) following general procedure A. Yield 70 %; light yellow solid, mp 99ꢀ101 C; Rf
= 0.65 (SiO2, Hexanes); 1H NMR (500 MHz, CDCl3) δ 7.62 (s, 1H), 7.55ꢀ7.49 (m, 2H), 7.46
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(d, J = 8.4 Hz, 1H), 7.43ꢀ7.37 (m, 3H), 7.37ꢀ7.25 (m, 5H), 6.42 (s, 1H), 4.14 (s, 2H); C
NMR (100 MHz, CDCl3) δ 158.9, 154.8, 140.4, 137.2, 135.1, 133.0, 129.5, 129.0, 128.9,
128.7, 128.7, 126.9, 123.0, 119.0, 111.2, 103.6, 35.1; IR (KBr) ν 3019, 1622, 1385, 1155,
669 cmꢀ1; HRMS (APCIꢀFTMS) calcd for C21H16ClO[M + H]+ 319.0890, found 319.0883.
2-benzyl-5-(4-ethylphenyl)benzofuran (2ar): 2ar (0.235 g) was obtained from 1ar (0.328
o
g, 1 mmol) following general procedure A. Yield 75 %; white solid, mp 100ꢀ102 C; Rf =
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0.61 (SiO2, Hexane); H NMR (500 MHz, CDCl3) δ 7.76(s, 1H), 7.55ꢀ7.50 (m, 2H), 7.47ꢀ
7.42 (m, 2H), 7.38ꢀ7.31 (m, 4H), 7.30ꢀ7.25 (m, 3H), 6.42 (d, J = 0.5 Hz, 1H), 4.13 (s, 2H),
2.71 (q, J = 7.6 Hz, 2H), 1.29 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 158.5,
154.6, 142.9, 139.3, 137.3, 136.3, 129.4, 129.0, 128.7, 128.3, 127.4, 126.9, 123.1, 118.9,
111.0, 103.7, 35.2, 28.6, 15.7; IR (KBr) ν 3019, 1621, 1406, 1155, 699 cmꢀ1; HRMS (DARTꢀ
TOF) calcd for C23H21O[M + H]+ 313.1592, found 313.1607.
2-benzylnaphtho[1,2-b]furan (2as): 2as (0.150 g) was obtained from 1as (0.274 g, 1 mmol)
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following general procedure A. Yield 58 %; Brown gum; Rf = 0.56 (SiO2, Hexanes); H
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NMR (400 MHz, CDCl3) δ 8.06ꢀ8.03 (m, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 9.0 Hz,
1H), 7.59 (dd, J = 8.9, 0.7 Hz, 1H), 7.56ꢀ7.51 (m, 1H), 7.47ꢀ7.42 (m, 1H), 7.37ꢀ7.33 (m, 4H),
7.31ꢀ7.26 (m, 1H), 6.87 (d, J = 0.8 Hz, 1H), 4.22 (s, 2H); 13C NMR (100 MHz, CDCl3) δ
157.2, 152.4, 137.5, 130.3, 129.0, 128.8, 127.6, 126.9, 126.1, 124.3, 124.3, 124.0, 123.5,
112.3, 102.6, 35.2; IR (neat) ν 2399, 1407, 1384, 1155, 928, 669 cmꢀ1; HRMS (DARTꢀTOF)
calcd for C19H15O[M + H]+ 259.1123, found 259.1127.
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5-(2-benzylbenzofuran-5-yl)benzo[d][1,3]dioxole (2at): 2at (0.240 g) was obtained from
1as (0.344 g, 1 mmol) following general procedure A. Yield 73 %; Brown gum; Rf = 0.55
(SiO2, 2% EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 1.5 Hz, 1H), 7.42 (d,
J = 8.5 Hz, 1H), 7.36 (d, J = 1.8 Hz, 1H), 7.35ꢀ7.34 (m, 1H), 7.33ꢀ7.30 (m, 3H), 7.29ꢀ7.26
(m, 1H), 7.07ꢀ7.03 (m, 2H), 6.88 (d, J = 8.0 Hz, 1H), 6.40 (d, J = 0.8 Hz, 1H), 5.99 (s, 2H)
4.12 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 158.6, 154.5, 148.1, 146.8, 137.2, 136.3, 136.1,
129.4, 129.0, 128.7, 126.9, 123.0, 120.9, 118.8, 111.0, 108.6, 108.1, 103.6, 101.2, 35.1; IR
(neat) ν 3019, 1621, 1505, 1405, 1384, 1155, 668 cmꢀ1; HRMS (DARTꢀTOF) calcd for
C22H17O3[M + H]+ 329.1178, found 329.1192.
2-benzyl-5-(6-methoxynaphthalen-2-yl)benzofuran (2au): 2au (0.242 g) was obtained
from 1au (0.380 g, 1 mmol) following general procedure A. Yield 66 %; white solid mp 109ꢀ
111 oC; Rf = 0.51 (SiO2, 2% EtOAc/Hexanes); 1H NMR (500 MHz, CDCl3) δ 7.95 (d, J = 1.2
Hz, 1H), 7.82ꢀ7.70 (m, 4H), 7.58ꢀ7.46 (m, 2H), 7.37ꢀ7.31 (m, 4H), 7.29ꢀ7.26 (m, 1H), 7.19ꢀ
7.14 (m, 2H), 6.44 (d, J = 0.7 Hz, 1H), 4.14 (s, 2H), 3.94 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 158.6, 157.7, 154.7, 137.3, 137.1, 136.4, 133.6, 129.7, 129.5, 129.3, 129.0, 128.7,
127.3, 126.9, 126.6, 125.8, 123.3, 119.2, 119.1, 111.2, 105.7, 55.4, 35.2; IR (KBr) ν 3019,
2926, 1405, 1155, 1068, 669 cmꢀ1; HRMS (DARTꢀTOF) calcd for C26H21O2 [M + H]+
365.1542, found 365.1557.
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2-(4-methylbenzyl)benzofuran11a (2ba): 2ba (0.189 g) was obtained from 1ba (0.238 g, 1
mmol) following general procedure A. Yield 85 %; colorless gum; Rf = 0.76 (SiO2, Hexane);
1H NMR (400 MHz, CDCl3) δ 7.50ꢀ7.45 (m, 1H), 7.43ꢀ7.40 (m, 1H), 7.20ꢀ7.17 (m, 4H),
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CDCl3) δ 158.2, 155.0, 136.4, 134.2, 129.4, 128.9, 123.4, 122.6, 120.5, 111.0, 103.3, 34.7,
21.2;
2-(4-butylbenzyl)benzofuran (2ca): 2ca (0.220 g) was obtained from 1ca (0.280 g, 1 mmol)
following general procedure A. Yield 83 %; colorless oil; Rf = 0.72 (SiO2, Hexane); 1H NMR
(400 MHz, CDCl3) δ 7.53ꢀ7.48 (m, 1H), 7.48ꢀ7.42 (m, 1H), 7.29ꢀ7.14 (m, 6H), 6.40 (d, J =
0.8 Hz, 1H), 4.11 (s, 2H), 2.64 (q, J = 7.7 Hz, 2H), 1.69ꢀ1.59 (m, 2H), 1.45ꢀ1.35 (m, 2H),
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0.97 (t, J = 7.3 Hz, 3H); C NMR (100 MHz, CDCl3) δ 158.2, 155.1, 141.5, 134.5, 129.0,
128.8, 128.7, 123.4, 122.6, 120.5, 111.0, 103.3, 35.4, 34.7, 33.7, 22.5, 14.0; IR (neat) ν 2958,
2858, 1513, 1384, 1159, 1070, 954, 668 cmꢀ1; HRMS (DARTꢀTOF) calcd for C19H21O[M +
H]+ 265.1592, found 265.1604.
2-(4-(tert-butyl)benzyl)benzofuran (2da): 2da (0.227 g) was obtained from 1da (0.280 g, 1
1
mmol) following general procedure A. Yield 86 %; yellow oil; Rf = 0.64 (SiO2, Hexane); H
NMR (400 MHz, CDCl3) δ 7.53ꢀ7.47 (m, 1H), 7.43 (d, J = 7.9 Hz, 1H), 7.41ꢀ7.35 (m, 2H),
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7.31ꢀ7.16 (m, 4H), 6.41 (d, J = 0.8 Hz, 1H), 4.11 (s, 2H) 1.34 (s, 9H); C NMR (100 MHz,
CDCl3) δ 158.1, 155.1, 149.7, 134.3, 129.0, 128.6, 125.6, 123.4, 122.6, 120.5, 111.0, 103.0,
34.6, 31.5, 29.8; IR (neat) ν 2965, 1454, 1328, 1253, 1068, 668 cmꢀ1; HRMS (DARTꢀTOF)
calcd for C19H21O[M + H]+ 265.1592, found 265.1603.
2-(4-methoxybenzyl)benzofuran11a (2ea): 2ea (0.215 g) was obtained from 1ea (0.254 g, 1
mmol) following general procedure A. Yield 90 %; brown gum; Rf = 0.54 (SiO2, 2%
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EtOAc/Hexanes); H NMR (400 MHz, CDCl3) δ 7.56ꢀ7.37 (m, 2H), 7.32ꢀ7.11 (m, 4H), 6.89
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(dd, J = 7.2, 0.7 Hz, 2H), 6.37 (d, J = 0.8 Hz, 1H), 4.07 (s, 2H), 3.81 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 158.6, 158.4, 155.1, 130.0, 129.4, 128.9, 123.4, 122.6, 120.5, 114.1, 111.0,
103.2, 55.3, 34.2
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2-(3-methoxybenzyl)benzofuran (2fa): 2fa (0.200 g) was obtained from 1fa (0.200 g, 1
mmol) following general procedure A. Yield 84 %; colorless gum; Rf = 0.53 (SiO2, 2%
EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.49ꢀ7.45 (m, 1H), 7.43ꢀ7.39 (m, 1H), 7.27ꢀ
7.14 (m, 3H), 6.92ꢀ6.88 (m, 1H), 6.88ꢀ6.84 (m, 1H), 6.81 (dd, J = 8.2, 2.1 Hz, 1H), 6.39 (d, J
= 0.8 Hz, 1H), 4.09 (s, 2H), 3.79 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.9, 157.7, 155.1,
138.9, 129.7, 128.9, 123.5, 122.6, 121.4, 120.5, 114.8, 112.2, 111.0, 103.5, 55.3, 35.1; IR
(neat) ν 2927, 1489, 1455, 1155, 955, 669 cmꢀ1; HRMS (DARTꢀTOF) calcd for C16H15O2[M
+ H]+ 239.1072, found 239.1078.
2-(3,4-dimethoxybenzyl)benzofuran (2ga): 2ga (0.247 g) was obtained from 1ga (0.284 g,
1 mmol) following general procedure A. Yield 92 %; light yellow oil; Rf = 0.53 (SiO2, 5%
EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.51ꢀ7.45 (m, 1H), 7.49ꢀ7.39 (m, 1H), 7.24ꢀ
7.15 (m, 2H), 6.88ꢀ6.80 (m, 3H), 6.37 (d, J = 0.9 Hz, 1H), 4.06 (s, 2H), 3.87 (s, 3H), 3.86 (s,
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3H); C NMR (100 MHz, CDCl3) δ 158.2, 155.0, 149.1, 148.0, 129.8, 128.9, 123.5, 122.6,
121.1, 120.5, 112.3, 111.4, 111.0, 103.0, 56.0, 55.9, 34.7; IR (neat) ν 2927, 1638, 1514, 1216,
1154, 1026, 669 cmꢀ1; HRMS (DARTꢀTOF) calcd for C17H17O3[M + H]+ 269.1178, found
269.1189.
2-(4-fluorobenzyl)benzofuran11a (2ha); 2ha (0.168 g) was obtained from 1ha (0.242 g, 1
mmol) following general procedure A. Yield 74 %; colorless oil; Rf = 0.77 (SiO2, Hexane);
1H NMR (400 MHz, CDCl3) δ 7.51ꢀ7.46 (m, 1H), 7.44ꢀ7.39 (m, 1H), 7.29ꢀ7.24 (m, 2H),
7.23ꢀ7.16 (m, 2H), 7.05ꢀ6.98 (m, 2H), 6.37 (d, J = 0.8 Hz, 1H), 4.08 (s, 2H); 13C NMR (100
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MHz, CDCl3) δ 161.9 (d, J = 244 Hz), 157.6, 155.1, 133.0, 130.5 (d, J = 8 Hz), 128.8, 123.6,
122.7, 120.6, 115.5 (d, J = 21 Hz), 111.0, 103.5, 34.3;
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2-(3-chlorobenzyl)benzofuran (2ia):11a 2ia (0.167 g) was obtained from 1ia (0.258 g, 1
mmol) following general procedure A. Yield 69 %; colorless oil; Rf = 0.81 (SiO2, Hexane);
1H NMR (400 MHz, CDCl3) δ 7.52ꢀ7.48 (m, 1H), 7.44ꢀ7.40 (m, 1H), 7.30 (s, 1H), 7.27ꢀ7.18
(m, 5H), 6.42 (d, J = 0.8 Hz, 1H), 4.09 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 156.8, 155.2,
139.4, 134.6, 129.9, 129.1, 128.8, 127.1, 123.8, 122.8, 120.6, 111.1, 103.8, 34.7.
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2-(thiophen-2-ylmethyl)benzofuran (2ja): 2ja (0.175 g) was obtained from 1ja (0.230 g, 1
mmol) following general procedure A. Yield 82 %; Brown oil; Rf = 0.63 (SiO2, Hexanes); 1H
NMR (400 MHz, CDCl3) δ 7.53ꢀ7.47 (m, 1H), 7.46ꢀ7.40 (m, 1H), 7.25ꢀ7.16 (m, 3H), 7.01ꢀ
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6.93 (m, 2H), 6.48 (d, J = 0.9 Hz, 1H), 4.30 (s, 2H); C NMR (100 MHz, CDCl3) δ 156.8,
155.0, 139.3, 128.8, 127.0, 126.1, 124.5, 123.7, 122.7, 120.7, 111.1, 103.4, 29.3; IR (neat) ν
2924, 1780, 1301, 1073, 952,850, 699 cmꢀ1; HRMS (APCIꢀFTMS) calcd for C13H11OS[M +
H]+ 215.0531, found 215.0525.
2-butylbenzofuran11b (2ka); 2ka (0.133 g) was obtained from 1ka (0.190 g, 1 mmol)
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following general procedure A. Yield 76 %; light brown oil; Rf = 0.85 (SiO2, Hexane); H
NMR (400 MHz, CDCl3) δ 7.50ꢀ7.45 (m, 1H), 7.42ꢀ7.38 (m, 1H), 7.22ꢀ7.14 (m, 2H), 6.37 (d,
J = 0.9 Hz, 1H), 2.77 (t, J = 7.5 Hz, 2H), 1.78ꢀ1.68 (m, 2H), 1.47ꢀ1.38 (m, 2H), 0.95 (t, J =
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7.3 Hz, 3H); C NMR (100 MHz, CDCl3) δ 159.9, 154.7, 129.1, 123.1, 122.4, 120.2, 110.8,
101.8, 29.9, 28.2, 22.4, 13.9;
2-heptylbenzofuran11b (2la): 2la (0.169 g) was obtained from 1la (0.232 g, 1 mmol)
following general procedure A. Yield 78 %; colorless oil, Rf = 0.84 (SiO2, Hexane); 1H NMR
(400 MHz, CDCl3) δ 7.49ꢀ7.45 (m, 1H), 7.43ꢀ7.39 (m, 1H), 7.22ꢀ7.14 (m, 2H), 6.37 (d, J =
0.8 Hz, 1H), 2.80ꢀ2.73 (m, 2H), 1.80ꢀ1.69 (m, 2H), 1.45ꢀ1.27 (m, 8H), 0.89 (t, J = 6.8 Hz,
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3H); C NMR (100 MHz, CDCl3) δ 159.9, 154.7, 129.1, 123.1, 122.4, 120.2, 110.8, 101.8,
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2-undecylbenzofuran (2ma): 2ma (0.204 g) was obtained from 1ma (0.288 g, 1 mmol)
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following general procedure A. Yield 75 %; Yellow oil; Rf = 0.81 (SiO2, Hexane); H NMR
(400 MHz, CDCl3) δ 7.05ꢀ7.45 (m, 1H), 7.43ꢀ7.38 (m, 1H), 7.22ꢀ7.14 (m, 2H), 6.37 (d, J =
0.8 Hz, 1H), 2.76 (t, J = 7.5 Hz, 2H), 1.81ꢀ1.67 (m, 2H), 1.41ꢀ1.20 (m, 16H), 0.88 (t, J = 6.8
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 159.9, 154.7, 129.1, 123.1, 122.4, 120.2, 110.8,
101.8, 32.0, 29.7, 29.7, 29.6, 29.5, 29.4, 29.3, 28.6, 27.8, 22.8, 14.2; IR (neat) ν 2854, 2400,
1454, 1156, 1069, 669 cmꢀ1; HRMS (APCIꢀFTMS) calcd for C19H29O[M + H]+ 273.2218,
found 273.2209.
2-(cyclopentylmethyl)benzofuran11c (2na): 2na (0.166 g) was obtained from 1na (0.216 g,
1 mmol) following general procedure A. Yield 83 %; light yellow gum Rf = 0.72 (SiO2,
Hexane); 1H NMR (400 MHz, CDCl3) δ 7.50ꢀ7.45 (m, 1H), 7.43ꢀ7.38 (m, 1H), 7.23ꢀ7.14 (m,
2H), 6.37 (d, J = 0.8 Hz, 1H), 2.75 (d, J = 7.4 Hz, 2H), 2.39ꢀ2.23 (m, 1H), 1.87ꢀ1.78 (m, 2H),
1.69ꢀ1.61 (m, 2H), 1.60ꢀ1.53 (m, 2H), 1.31ꢀ1.25 (m, 2H); 13C NMR (100 MHz, CDCl3) δ
159.5, 154.7, 129.1, 123.1, 122.4, 120.2, 110.8, 102.3, 38.7, 34.6, 32.6, 25.2;
2-(cyclohexylmethyl)benzofuran (2oa): 2oa (0.182 g) was obtained from 2oa (0.230 g, 1
mmol) following general procedure A. Yield 85 %; Yellow gum; Rf = 0.82 (SiO2, Hexane);
1H NMR (400 MHz, CDCl3) δ 7.51ꢀ7.45 (m, 1H), 7.44ꢀ7.38 (m, 1H), 7.23ꢀ7.14 (m, 2H), 6.37
(d, J = 0.6 Hz, 1H), 2.64 (d, J = 6.6 Hz, 2H), 1.82ꢀ1.63 (m, 4H), 1.31ꢀ1.10 (m, 4H), 1.08ꢀ0.94
(m, 2H); 13C NMR (100 MHz, CDCl3) δ 158.6, 154.8, 129.1, 123.1, 122.4, 120.2, 110.8,
102.9, 37.1, 36.4, 33.3, 26.5, 26.3; IR (neat) ν 2853, 1454, 1254, 1157, 948, 929, 669 cmꢀ1;
HRMS (APCIꢀFTMS) calcd for C15H19O[M + H]+ 215.1436, found 215.1429.
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(Z)-2-benzylidene-2,3-dihydrobenzofuran-3-ol4f (3): Yield 76 %; white solid, mp 109ꢀ110
oC; Rf = 0.47 (SiO2, 5% EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 7.3 Hz,
2H), 7.50 (d, J = 7.5 Hz, 1H), 7.41ꢀ7.32 (m, 3H), 7.28ꢀ7.21 (m, 1H), 7.13ꢀ7.05 (m, 2H), 6.01
(d, J = 1.1 Hz, 1H), 5.76 (d, J = 6.0 Hz, 1H), 2.19 ( d, J = 7.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 157.8, 157.1, 134.6, 130.7, 128.8, 128.5, 127.0, 126.9, 125.7, 123.0, 110.7, 106.1,
72.6.
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General Procedure B for the Synthesis of 2-(azido(phenyl)methyl)benzofurans (4a-f)
from 2-benzyl benzofurans (2aa, 2da, 2ga, 2ap, 2af, 2ak) taking Synthesis of 4a as an
example: To a stirred solution of 2ꢀbenzyl benzofuran (208 mg, 1 mmol, 1 eq) in 4 mL of
AcOH was added DDQ (454 mg, 2 mmol, 2 eq), TMSN3(172.5 mg, 1.5 mmol, 1.5 eq) at
room temperature. The reaction mixture was stirred at room temperature until complete
conversion of starting material (2h for 4a, 4(d-f), 1h for 4(bꢀc)). The reaction mixture was
neutralized with Na2CO3 (2 g), and evaporated under reduced pressure. The residue was
diluted with water (20ml) and extracted with CH2Cl2 (2x15ml). The combined extracts were
dried over Na2SO4. After removal of the solvent under reduced pressure the crude material
was purified on silica using 5% EtoAc/hexane to get 4a (214 mg, 86 %) as yellow oil
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2-(azido(phenyl)methyl)benzofuran (4a): Rf = 0.60 (SiO2, 2% EtOAc/Hexanes); H NMR
(400 MHz, CDCl3) δ 7.58ꢀ7.49 (m, 1H), 7.49ꢀ7.32 (m, 6H), 7.32ꢀ7.16 (m, 2H), 6.59 (s, 1H),
5.77 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 155.4, 154.9, 136.3, 129.0, 127.8, 127.7, 124.8,
123.1, 121.3, 111.5, 105.6, 62.7; IR (neat) ν 3019, 2102, 1385, 1069, 668 cmꢀ1; HRMS (ESIꢀ
TOF) calcd for C15H12NO[M + H – N2]+ 222.0919, found 222.0911.
2-(azido(4-(tert-butyl)phenyl)methyl)benzofuran (4b): (4b) (0.232 g) was obtained from
2da (0.264 g, 1 mmol) following general procedure B. Yield 76 %; yellow gum; Rf = 0.5
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(SiO2, 2% EtOAc/Hexanes); H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 7.5 Hz, 1H), 7.52ꢀ
7.43 (m, 3H), 7.43ꢀ7.35 (m, 2H), 7.35ꢀ7.20 (m, 2H), 6.64 (s, 1H), 5.78 (s, 1H), 1.36 (s, 9H);
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13C NMR (100 MHz, CDCl3) δ 155.4, 155.1, 152.0, 133.3, 129.8, 127.9, 125.9, 124.7, 123.1,
121.3, 111.5, 105.5, 62.5, 34.8, 31.4; IR (neat) ν 1644,1217, 1069, 668 cmꢀ1; HRMS (ESIꢀ
TOF) calcd for C19H20NO[M + H – N2]+ 278.1545, found 278.1535.
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2-(azido(3,4-dimethoxyphenyl)methyl)benzofuran (4c): (4c) (0.231 g) was obtained from
2ga (0.268 g, 1 mmol) following general procedure B. Yield 75 %; yellow oil; Rf = 0.45
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(SiO2, 5% EtOAc/Hexanes); H NMR (400 MHz, CDCl3) δ 7.62ꢀ7.52 (m, 1H), 7.48 (d, J =
8.2 Hz, 1H), 7.36ꢀ7.19 (m, 2H), 7.05ꢀ6.95 (m, 2H), 6.91 (d, J = 8.1 Hz, 1H), 6.63 (s, 1H),
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5.76 (s, 1H), 3.92 (s, 3H), 3.91 (s, 3H); C NMR (100 MHz, CDCl3) δ 155.3, 155.1, 149.6,
149.4, 128.7, 127.8, 124.7, 123.1, 121.3, 120.3, 111.5, 111.2, 110.7, 105.3, 62.6, 56.0, 56.0;
IR (neat) ν 3019, 2102, 1730, 1645, 1156, 669 cmꢀ1; HRMS (ESIꢀTOF) calcd for
C17H16NO3[M + H – N2]+ 282.1130, found 282.1134.
2-(azido(phenyl)methyl)-5-phenylbenzofuran (4d): (4d) (0.276 g) was obtained from 2ap
(0.284 g, 1 mmol) following general procedure B. Yield 85 %; white solid mp 97ꢀ99 oC; Rf =
0.5 (SiO2, 2% EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.76ꢀ7.72 (m, 1H), 7.64ꢀ7.58
(m, 2H), 7.55ꢀ7.50 (m, 2H), 7.50ꢀ7.32 (m, 8H), 6.67 (s, 1H), 5.81 (s, 1H); 13C NMR (100
MHz, CDCl3) δ 155.6, 155.0, 141.5, 136.9, 136.3, 129.0, 128.8, 128.3, 127.7, 127.5, 127.0,
124.5, 119.8, 111.6, 105.8, 62.7; IR (neat) ν 1644, 1385, 1218, 1070, 668 cmꢀ1; HRMS (ESIꢀ
TOF) calcd for C21H16NO[M + H – N2]+ 298.1232, found 298.1231.
2-(azido(phenyl)methyl)-5-chlorobenzofuran (4e): (4e) (0.226 g) was obtained from 2af
(0.242 g, 1 mmol) following general procedure B. Yield 80 %; yellow oil; Rf = 0.6 (SiO2, 2%
EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.53ꢀ7.48 (m, 1H), 7.46ꢀ7.40 (m, 5H), 7.39ꢀ
7.33 (m, 1H), 7.24 (dd, J = 8.6, 2.1 Hz, 1H); 6.56 (s, 1H), 5.77 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 156.6, 153.7, 136.0, 129.1, 129.1, 129.0, 128.7, 127.7, 125.0, 112.5, 105.1, 62.6; IR
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(neat) ν 1644, 1385, 1219, 1075, 668 cmꢀ1; HRMS (ESIꢀTOF) calcd for C15H11ClNO[M + H
– N2]+ 256.0529, found 256.0513.
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2-(azido(phenyl)methyl)-5-methoxybenzofuran (4f): (4f) (0.218 g) was obtained from 2ak
(0.238 g, 1 mmol) following general procedure B. Yield 78 %; yellow oil; Rf = 0.6 (SiO2,
10% EtOAc/Hexanes); 1H NMR (500 MHz, CDCl3) δ 7.46ꢀ7.37 (m, 5H), 7.36ꢀ7.31 (m, 1H),
6.99 (d, J = 2.5 Hz, 1H), 6.89 (dd, J = 8.9, 2.6 Hz, 1H), 6.54 (s, 1H), 5.75 (s, 1H), 3.82 (s,
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3H); C NMR (100 MHz, CDCl3) δ 156.2, 155.7, 150.4, 136.4, 129.0, 128.9, 128.3, 127.7,
113.5, 112.0, 105.7, 103.8, 62.7, 56.0; IR (neat) ν 3019, 2013, 1638, 1385, 1070, 668 cmꢀ1;
HRMS (ESIꢀTOF) calcd for C16H14NO2[M + H – N2]+ 252.1025, found 252.1017.
General Procedure C for the Synthesis of 2-alkoxy benzofurans (5a-f) from 2-benzyl
benzofurans (2aa) taking Synthesis of 5a as an example:
To a stirred solution of 2aa (208 mg, 1 mmol, 1 eq) in 4 mL of ROH: CH2Cl2 (1:1) was
added DDQ (454 mg, 2 mmol, 2 eq), at room temperature. The reaction mixture was stirred at
room temperature until complete conversion of starting material monitored by TLC. (8h for
5a-b, 12h for 5c-d, 20h for 5e-5f). The reaction mixture was evaporated under reduced
pressure. The residue was diluted with water (20ml) and extracted with CH2Cl2 (2x15ml).
The combined extracts were dried over Na2SO4. After removal of the solvent under reduced
pressure the crude material was purified on silica using 2%ꢀ5% EtoAc/hexanes for (5a-5f) to
get 5a (167 mg, 70 %) as a yellow oil.
2-(methoxy(phenyl)methyl)benzofuran (5a): Yellow oil; Rf = 0.62 (SiO2, 5%
EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.53ꢀ7.43 (m, 4H), 7.42ꢀ7.32 (m, 3H), 7.27ꢀ
7.16 (m, 2H), 6.50 (s, 1H), 5.40 (s, 1H), 3.47 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.1,
155.3, 138.6, 128.6, 128.4, 128.1, 127.4, 124.3, 122.8, 121.1, 111.5, 105.1, 79.6, 51.4; IR
(neat) ν 3019, 1638, 1385, 1154, 1069, 669 cmꢀ1; HRMS (DARTꢀTOF) calcd for C15H11O[M
– OCH3]+ 207.0810 found 207.0805.
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2-(ethoxy(phenyl)methyl)benzofuran (5b): 5b (0.187 g) was obtained from 2aa (208 g, 1
mmol) following general procedure C. Yield 74 %; colorless oil; Rf = 0.64 (SiO2, 5%
EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.52ꢀ7.47 (m, 3H), 7.46ꢀ7.43 (m, 1H), 7.41ꢀ
7.31 (m, 3H), 7.24ꢀ7.16 (m, 2H), 6.54 (t, J = 0.7 Hz, 1H), 5.52 (s, 1H), 3.71ꢀ3.58 (m, 2H),
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1.30 (t, J = 7.0 Hz, 3H); C NMR (100 MHz, CDCl3) δ 157.6, 155.3, 139.2, 128.6, 128.2,
128.1, 127.3, 124.2, 122.8, 121.1, 111.5, 104.8, 77.7, 65.1, 15.4; IR (neat) ν 2400, 1385,
1155, 928, 669 cmꢀ1; HRMS (DARTꢀTOF) calcd for C15H11O[M – OC2H5]+ 207.0810 found
207.0806.
2-(phenyl(propoxy)methyl)benzofuran (5c): 5c (0.189 g) was obtained from 2aa (0.208 g,
1 mmol) following general procedure C. Yield 71 %; yellow gum; Rf = 0.68 (SiO2, 5%
EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.53ꢀ7.48 (m, 3H), 7.47ꢀ7.44 (m, 1H), 7.41ꢀ
7.32 (m, 3H), 7.27ꢀ7.17 (m, 2H), 6.56 (s, 1H), 5.51 (s, 1H), 3.60ꢀ3.68 (m, 2H), 1.76ꢀ1.66 (m,
2H), 0.97 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 157.7, 155.3, 139.3, 128.5,
128.2, 127.3, 124.2, 122.7, 121.1, 111.5, 104.7, 77.8, 71.4, 23.1, 10.7; IR (neat) ν 1639, 1385,
1154, 1069, 669 cmꢀ1; HRMS (DARTꢀTOF) calcd for C15H11O[M – OC3H7]+ 207.0810 found
207.0809.
2-(butoxy(phenyl)methyl)benzofuran (5d): 5d (0.205 g) was obtained from 2aa (0.208 g, 1
mmol) following general procedure C. Yield 73 %; colorless gum; Rf = 0.69 (SiO2, 5%
EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.53ꢀ7.42 (m, 4H), 7.41ꢀ7.29 (m, 3H), 7.28ꢀ
7.15 (m, 2H), 6.55 (s, 1H), 5.50 (s, 1H), 3.63ꢀ3.51 (m, 2H), 1.71ꢀ1.62 (m, 2H), 1.48ꢀ1.38 (m,
2H), 0.92 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 157.7, 155.3, 139.3, 128.5,
128.2, 127.3, 124.2, 122.7, 121.1, 111.5, 104.7, 77.9, 69.6, 32.0, 19.5, 14.0; IR (neat) ν 3019,
1638, 1385, 1154, 1068, 669 cmꢀ1; HRMS (DARTꢀTOF) calcd for C15H11O[M – OC4H9]+
207.0810 found 207.0804.
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2-(phenoxy(phenyl)methyl)benzofuran (5e): 5e (0.177 g) was obtained from 2aa (0.208 g,
1 mmol) following general procedure C. Yield 59 %; brown gum; Rf = 0.46 (SiO2, 2%
EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.60ꢀ7.53 (m, 2H), 7.52ꢀ7.49 (m, 2H), 7.42ꢀ
7.33 (m, 3H), 7.29ꢀ7.16 (m, 4H), 7.05ꢀ6.99 (m, 2H), 6.95 (t, J = 2.4 Hz, 1H), 6.58 (s, 1H),
6.35 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 157.9, 156.3, 155.3, 138.2, 129.6, 128.8, 128.6,
128.1, 127.2, 124.5, 122.9, 121.7, 121.3, 116.3, 111.6, 105.4, 76.3; IR (neat) ν 2924, 1638,
1216, 1154, 1068, 669 cmꢀ1; HRMS (APCIꢀFTMS) calcd for C15H11O[M – OC6H5]+
207.0810 found 207.0806.
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2-(phenyl(prop-2-yn-1-yloxy)methyl)benzofuran (5f): 5f (0.160 g) was obtained from 2aa
(0.208 g, 1 mmol) following general procedure C. Yield 61 %; colorless oil; Rf = 0.54 (SiO2,
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2% EtOAc/Hexanes); H NMR (400 MHz, CDCl3) δ 7.54ꢀ7.48 (m, 3H), 7.47ꢀ7.43 (m, 1H),
7.42ꢀ7.34 (m, 3H), 7.28ꢀ7.17 (m, 2H), 6.62 (s, 1H), 5.83 (s, 1H), 4.31ꢀ4.19 (m, 2H), 2.49 (t, J
= 2.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 156.2, 155.4, 137.9, 128.7, 128.6, 128.0,
127.7, 124.5, 122.9, 121.2, 111.6, 105.7, 79.3, 75.9, 75.3, 56.2; IR (neat) ν3019, 1639, 1385,
1154, 669 cmꢀ1; HRMS (DARTꢀTOF) calcd for C15H11O[M – OC3H3]+ 207.0810 found
207.0808.
Procedure for the Synthesis of benzofuran-2-yl(phenyl)methanol (6):12 To a stirred
solution of 2ꢀbenzyl benzofuran (208 mg, 1 mmol, 1 eq) in 3 mL of Ac2OH: AcOH (1:1) was
added DDQ (454 mg, 2 mmol, 2 eq), at room temperature. The reaction mixture was stirred at
room temperature until complete conversion of starting material (18h). The reaction mixture
was neutralized with Na2CO3 (2 g), and evaporated under reduced pressure. The residue was
diluted with water (20ml) and extracted with CH2Cl2 (2x15ml). The combined extracts were
dried over Na2SO4. After removal of the solvent under reduced pressure the crude material
was purified on silica using 5% EtoAc/hexane to get 6 (159 mg, 71 %) as yellow oil. Rf =
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0.46 (SiO2, 5% EtOAc/Hexanes); H NMR (400 MHz, CDCl3) δ 7.53ꢀ7.48 (m, 3H), 7.46ꢀ
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7.34 (m, 4H), 7.28ꢀ7.17 (m, 2H), 6.53 (t, J = 0.8 Hz, 1H), 5.96 (s, 1H), 2.54 (bs, 1H); C
NMR (100 MHz, CDCl3) δ 158.6, 155.2, 140.4, 128.7, 128.5, 128.1, 126.9, 124.4, 122.9,
121.2, 111.4, 104.1, 70.8; IR (neat) ν 3400, 1638, 1385, 1217, 1154, 668 cmꢀ1.
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Procedure for the Synthesis of 3-(benzofuran-2-yl(phenyl)methyl)-2-benzyl benzofuran
(7): To a stirred solution of 2ꢀbenzyl benzofuran (2aa) (104 mg, 0.5 mmol, 0.5 eq) in 2 mL of
AcOH was added DDQ (227 mg, 1 mmol, 2 eq), at room temperature. The reaction mixture
was stirred at room temperature until complete conversion of starting material monitored by
TLC (20h). The reaction mixture was neutralized with Na2CO3 (1 g), and evaporated under
reduced pressure. The residue was diluted with water (10ml) and extracted with CH2Cl2
(2x10ml). The combined extracts were dried over Na2SO4. After removal of the solvent under
reduced pressure the crude material was purified on silica using 5% EtoAc/hexane to get 7
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(84 mg, 82%) as yellow gum. Rf = 0.62 (SiO2, 5% EtOAc/Hexanes); H NMR (400 MHz,
CDCl3) δ 7.48ꢀ7.44 (m, 1H), 7.41ꢀ7.36 (m, 2H), 7.31ꢀ7.24 (m, 5H), 7.23ꢀ7.13 (m, 9H), 7.07ꢀ
7.02 (m, 1H), 6.36 (s, 1H), 5.79 (s, 1H), 4.04 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 158.4,
155.1, 154.4, 153.8, 139.8, 137.4, 128.7, 128.7, 128.6, 128.5, 127.3, 126.7, 123.9, 123.7,
122.8, 122.5, 120.8, 120.5, 115.1, 111.3, 111.1, 105.6, 41.7, 33.0; IR (neat) ν 3019, 1639,
1385, 1155, 1068, 668 cmꢀ1; HRMS (APCIꢀFTMS) calcd for C30H23O2 [M + H]+ 415.1698,
found 415.1689.
General Procedure for the Synthesis benzofuran-2-yl(phenyl)methanone (8):13 2ꢀbenzyl
benzofuran (104 mg, 0.5 mmol, 1 eq) in 2 mL DCE was added MnO2 (130 mg, 1.5 mmol, 3
eq). The reaction mixture was stirred under reflux for 2h. The reaction mass was filtered and
evaporated under reduced pressure. The crude residue was purified by column
chromatography on silica gel (100–200 mesh) with 5 %EtOAc/Hexane as the eluent to give
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the pure product (83 mg, 74 %) as white solid. mp 90ꢀ92 C; Rf = 0.51 (SiO2, 5%
EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ 8.09ꢀ8.01 (m, 2H), 7.73 (d, J = 7.9 Hz, 1H),
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7.68ꢀ7.60 (m, 2H), 7.57ꢀ7.46 (m, 4H), 7.37ꢀ7.30 (m, 1H); 13C NMR (100 MHz, CDCl3) δ
184.5, 156.1, 152.3, 137.3, 133.0, 129.5, 128.6, 128.5, 127.1, 124.1, 123.4, 116.6, 112.7.
Procedure for the Synthesis 2-benzyl-3-bromobenzofuran (9): To a stirred solution of 2ꢀ
benzyl benzofuran (2aa) (208 mg, 1 mmol, 1 eq) in 5 mL of CCl4 was added NꢀBromo
succinimide (266.8 mg, 1.5 mmol, 1.5 eq), at room temperature. The reaction mixture was
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stirred at 80 C until complete conversion of starting material monitored by TLC (12h). The
reaction mixture was diluted with water (20ml) and extracted with CH2Cl2 (2x15ml). The
combined extracts were dried over Na2SO4. After removal of the solvent under reduced
pressure the crude material was purified on silica using 2% EtoAc/hexane to get 9 (194 mg,
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68 %) as Brown oil. Rf = 0.68 (SiO2, Hexane); H NMR (400 MHz, CDCl3) δ 7.53ꢀ7.45 (m,
1H), 7.44ꢀ7.37 (m, 1H), 7.36ꢀ7.22 (m, 7H), 4.19 (s, 2H); 13C NMR (100 MHz, CDCl3) δ
153.8, 153.8, 136.7, 128.8, 128.3, 126.9, 124.9, 123.3, 119.5, 111.4, 95.2, 33.0; IR (neat) ν
2926, 1405, 1216, 1155, 669 cmꢀ1; HRMS (APCIꢀFTMS) calcd for C15H11BrO.+[M].+
285.9988, found 285.9987.
General Procedure D for the Synthesis of 5-(benzofuran-2-yl)-1-phenyl-1H-tetrazoles
(10a-10b) from (2aa,2ea) taking Synthesis of 10a as an example:
To a stirred solution of 2ꢀbenzyl benzofuran (208 mg, 1 mmol, 1 eq) in 4 mL of CH3CN was
added CuI (19mg, 0.1 mmol, 0.1 eq), DDQ (454 mg, 2 mmol, 2 eq), TMSN3 (632 mg, 5.5
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mmol, 5.5 eq), 4 A MS (500 mg) at room temperature under nitrogen atmosphere. The
reaction mixture was stirred at 80 oC until complete conversion of starting material monitored
by TLC (12h). The reaction mixture was diluted with water (20ml) and extracted with EtOAc
(2x15ml). The combined extracts were dried over Na2SO4. After removal of the solvent under
reduced pressure the crude material was purified on silica using 20% EtoAc/hexane to get
10a (218 mg, 83 %) as brown gum.
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5-(benzofuran-2-yl)-1-phenyl-1H-tetrazole (10a): Rf = 0.5 (SiO2, 20% EtOAc/Hexanes); 1H
NMR (400 MHz, CDCl3) δ 7.72ꢀ7.58 (m, 4H), 7.58ꢀ7.50 (m, 2H), 7.48ꢀ7.42 (m, 1H), 7.42ꢀ
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7.34 (m, 1H), 7.33ꢀ7.23 (m, 1H), 7.15 (s, 1H); C NMR (100 MHz, CDCl3) δ 155.6, 147.0,
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140.3, 134.4, 131.1, 129.9, 127.2, 127.1, 125.9, 124.2, 122.4, 112.1, 111.4; IR (neat) ν 3019,
1645, 1069, 909, 669 cmꢀ1. HRMS (ESIꢀTOF) calcd for C15H11N4O[M + H]+ 263.0933, found
263.0934.
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5-(benzofuran-2-yl)-1-(4-methoxyphenyl)-1H-tetrazole (10b): (10b) (0.160 g) was
obtained from 2ea (0.238 g, 1 mmol) following general procedure D. Yield 55 %; yellow
gum; Rf = 0.46 (SiO2, 20% EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 7.5
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Hz, 1H), 7.54ꢀ7.34 (m, 4H), 7.34ꢀ7.21 (m, 1H), 7.18ꢀ6.98 (m, 3H), 3.93 (s, 3H); C NMR
(100 MHz, CDCl3) δ 161.5, 155.6, 147.2, 140.2, 136.8, 127.4, 127.2, 127.1, 124.1, 122.3,
115.0, 112.1, 111.1, 55.8; IR (neat) ν 3019, 1644, 1385, 1069, 909, 668 cmꢀ1; HRMS (ESIꢀ
TOF) calcd for C16H13N4O2[M + H]+ 293.1039, found 293.1031.
General Procedure E for the Synthesis of N-phenylbenzofuran-2-carboxamides (11b-c)
from (2ea, 2ga) taking 11b as an example:
To a stirred solution of 2ꢀ(4ꢀmethoxybenzyl)benzofuran (238 mg, 1 mmol, 1 eq) in 4 mL of
AcOH was added FeCl2 (12.5 mg, 0.1 mmol, 0.1 eq), DDQ (454 mg, 2 mmol, 2 eq),
TMSN3(230 mg, 2 mmol, 2 eq), H2O (36 mg, 2 mmol, 2 eq) at room temperature under
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nitrogen atmosphere. The reaction mixture was stirred at 60 C until complete conversion of
starting material (12). The reaction mixture was cooled to room temperature, neutralized with
Na2CO3 (2 g), and evaporated under reduced pressure. The residue was diluted with water
(20ml) and extracted with CH2Cl2 (2x15ml). The combined extracts were dried over Na2SO4.
After removal of the solvent under reduced pressure the crude material was purified on silica
using 8% EtoAc/hexane to get 11b (160 mg, 60 %) as yellow solid.
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