Cascade Rh(ii) and Yb(iii) catalyzed synthesis of substituted naphthofurans: Via transannulation of N -sulfonyl-1,2,3-triazoles with β-naphthols

Article abstract of DOI:10.1039/c8cc10306b

An efficient cascade Rh(ii) and Yb(iii) catalyzed transannulation of N-sulfonyl-1,2,3-triazoles with β-naphthols has been accomplished for the synthesis of substituted naphthofurans in good yields. The reaction involves the initial rhodium catalyzed insertion of azavinyl carbene into the O-H bond followed by ytterbium catalyzed annulative C-C bond formation and concomitant aerial oxidation. The developed reaction was successfully extended to phenols to afford substituted benzofurans. Furthermore, the synthetic utility of the method was demonstrated through the synthesis of important polyhetero aromatic compounds.

Full text of DOI:10.1039/c8cc10306b

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DOI: 10.1039/C8CC10306B
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Cascade Rh(II) and Yb(III) Catalyzed Synthesis of Substituted
Naphthofurans via Transannulation of N-Sulfonyl-1,2,3-triazoles
Received 00th January 20xx,
Accepted 00th January 20xx
with β-naphthols
DOI: 10.1039/x0xx00000x
Selvam Kaladevi, Mani Kamalraj, Minakshi Altia, Shanmugam Rajasekar and Pazhamalai
Anbarasan*
www.rsc.org/
An efficient cascade Rh(II) and Yb(III) catalyzed transannulation of
N-sulfonyl-1,2,3-triazoles with -naphthols have been
β
accomplished for the synthesis of substituted naphthofurans in
good yields. The reaction involves the initial rhodium catalyzed
insertion of azavinyl carbene into O-H bond followed by ytterbium
catalyzed annulative C-C bond formation and concomitant aerial
oxidation. The developed reaction was successfully extended to
the phenols to afford substituted benzofurans. Furthermore,
synthetic utility of the method was demonstrated through the
synthesis of important polyhetero aromatic compounds.
Figure 1. Biologically important naphthofurans.
For instance, Chen and co-workers reported the two-step
synthesis of benzofuran via initial C-H insertion followed by
oxidation.6 The similar approach was accomplished by Kang
and co-workes in single step employing the combination of
Rh(II) and Cu(I) catalysts.7 On the other hand, carbonyl
tethered triazole was utilized by Li and co-workers for the
synthesis of substituted furans.8 Substituted 3-aminofurans
were achieved from triazoles and propargyl alcohols by Huang
and co-workers via rhodium catalyzed insertion, thermal
Claisen rearrangement and gold catalyzed cyclization.9
Naphthofurans are vital heterocyclic motifs found in various
pharmacological drugs and natural products and also
employed as promising building blocks in organic synthesis.1
Representative examples of napththofurans are shown in
Figure 1. Due to the importance of naphthofuran frameworks,
various strategies were documented for the synthesis of
substituted naphthofurans.2 Most these strategies utilize
either β -naphthols or naphthoquinones as starting materials
and involve initial C-C bond formation followed by C-O bond
formation. However, these methods require synthesis of
prefunctionalized starting materials and harsh conditions.
Thus, development of new method for the construction of
substituted naphthofurans from readily accessible starting
material is highly desirable.
On the other hand, rhodium azavinyl carbene, a highly reactive
intermediate generated from readily accessible N-sulfonyl
1,2,3-triazole, has gained significant attention in recent years
due to its valuable contribution in the synthesis of diverse
polyheterocyclic compounds.3 Most of these methods were
focused on the synthesis of nitrogen based heterocycles4 and
only selected oxygen based heterocycles5 were demonstrated.
Particularly, constructions of substituted/fused furans are
rather limited.
Scheme 1. Synthesis of naphthofurans.
However,
synthesis
of
naphtho/benzofurans
from
corresponding phenol derivatives and N-sulfonyl-1,2,3-
triazoles was not documented. In continuation of our interest
in the development of efficient strategy for the synthesis of
various heterocycles utilizing rhodium azavinyl carbenes,10 we
herein disclose the Rh(II) and Yb(III) catalyzed synthesis of
naphthofurans from β-naphthols and N-sulfonyl-1,2,3-triazoles
via rhodium catalyzed insertion followed by ytterbium
catalyzed cyclization and oxidation (Scheme 1). In addition,
this method also demonstrates the efficiency of the cascade
catalysis employing more than one catalyst in one-pot.
a. Department of Chemistry, Indian Institute of Technology Madras, Chennai-
600036, India. Email: anbarasansp@iitm.ac.in. webpage:
https://home.iitm.ac.in/anbarasansp/
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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We commenced our studies employing N-sulfonyl triazoles 1a With the optimized conditions in hand, we nextViienwvAertsictliegOantleinde
with β-naphthol 2 as model substrates. Initial reaction of 1 the scope and generality of this reacDtiOoIn: 10w.1i0t3h9/sCu8bCsCt1i0tu30te6dB
equiv of 1a with 1 equiv of 2a in the presence of 2 mol % of triazoles. Alkyl substituted aryl containing N-sulfonyl-1,2,3-
Rh2(OAc)4 under N2 atmosphere in the absence of additive triazoles gave the corresponding naphthofuran derivatives (3a-
didn’t afford the expected product 3a. Subsequently, we were 3e) in good to excellent yields (Scheme 2). Halides (F and Cl)
pleased to find that the above reaction under O2 atmosphere and methoxy substituents were well tolerated to afford the
in the presence of 10 mol% of CuTC as an additive furnished corresponding naphthofurans 3f-3i and 3n-3o. Formation of
the desired product 3a in 45% along with significant amount of naphthyl substituted naphthofuran 3j was achieved in 61%
BINOL (50%) (Table 1, entry 1). Further investigation with yield from corresponding substituted triazole. Next,
various additives such as Cu(OAc)2 and Cu2O were failed to substitution on the nitrogen was examined. Changing the
improve the yield of 3a (Table 1, entry 2 and 3). Next, sulfonyl group at the N1 position of triazole moiety furnished
reactions were screened with AgOTf, Sc(OTf)3 and Yb(OTf)3 as the corresponding naphthofurans 3k-3m in ~55% yield. The
additive, which afforded 3a in 30, 31 and 40% yield, structure of the naphthofuran 3l was unambiguously
respectively (Table 1, entries 4-6).
confirmed by single crystal X-ray analysis.11 The present
method also works with less efficiency for the electron
withdrawing nitro and sensitive dioxolane substituted triazoles
and let to the formation of products 3o and 3p in low yield.
The low yield issue was address by introducing the Yb(OTf)3
after 3 h, where the formation of 3i, 3n-p was observed in the
improved yield.
Table 1. Transannulation of 1a with 2a: Optimization.[a]
Time
(h)
Yield
(%)[b]
Entry
1
Catalyst (mol %)
Rh2(OAc)4 (2)
Additive (mol %)
CuTC (10)
14
45
2
3
4
Rh2(OAc)4 (2)
Rh2(OAc)4 (2)
Cu(OAc)2 (10)
Cu2O (10)
14
12
20
36
Rh2(OAc)4 (2)
Rh2(OAc)4 (2)
Rh2(OAc)4 (2)
Rh2(OAc)4 (2)
AgOTf (10)
Sc(OTf)3 (10)
Yb(OTf)3 (10)
Yb(OTf)3 (20)
10
12
12
12
30
31
40
61
5
6
7
8
Rh2(OAc)4 (4)
Rh2(OAc)4 (4)
Yb(OTf)3 (20)
Ni(OTf)2 (20)
12
12
65
44
9
10
11
12
13[c]
14[c]
15[c]
16[c]
Rh2(OAc)4 (4)
Rh2(OAc)4 (4)
Rh2(OAc)4 (4)
Rh2(OAc)4 (4)
Rh2(Oct)4 (4)
Rh2(Piv)4 (4)
Rh2(esp)4 (4)
Hf(OTf)3 (20)
In(OTf)3 (20)
Cu(OTf)2 (20)
Yb(OTf)3 (20)
Yb(OTf)3 (20)
Yb(OTf)3 (20)
Yb(OTf)3 (20)
12
12
12
12
12
12
12
60
48
32
75
28
39
43
[a] Reaction conditions: 1a (0.35 mmol, 1 equiv), 2a (0.35 mmol, 1 equiv), Rh(II)-
cat., additive, toluene 110 °C, time. [b] All are isolated yields. [c] 2 equiv of 1a.
Increasing the catalyst loading to 4 mol% and additive loading
to 20 mol% further improved the yield of the naphthofuran 3a
(Table 1, entry 7 and 8). In attempt to further tune the
reaction condition with other metal triflates were unsuccessful
(Table 1, entries 9-12). To suppress the formation of BINOL,
the equivalence of triazole was increased to 2 equiv and the
formation of product was observed in 75% yield (Table 1, entry
13). Furthermore, various rhodium catalysts such as Rh2(Oct)4,
Rh2(Piv)4, and Rh2(esp)4 were also tested and gave the product
3a in 28% , 39% and 43% yield, respectively (Table 1, entries
14-16). Thus, entry 13 was chosen as optimal conditions for
the transannulation of 1a with 2a.
Scheme 2. Scope of triazoles. † Yb(OTf)3 was added after 3 h.
To further expand the scope of the developed method, the
reaction of diverse substituted β-naphthols with mesyl triazole
1a were investigated (Scheme 3). 6-Benzyloxy and 6-bromo β-
naphthols on reaction with 1a under the optimized conditions
afforded the products 3r and 3s in 37 and 45% yield.
Importantly, ethoxycarbonyl group substituted β-naphthols
underwent smooth reaction to give the products 3t and 3y in
75% and 62% yield, respectively. Similarly, substituted aryl
containing β-naphthols also furnished the corresponding
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naphthofurans 3u-3x in moderate to good yield. Formation of
furan annulated phenanthrene was achieved in 28% yield from
9-phenanthrol and 1b. Consequently, the efficiency of this
method was successfully extended to the synthesis of
benzofuran derivatives employing simple substituted phenols.
Thus, the reaction of 4-tert-butylphenol and 1a in the presence
of Rh2(OAc)4 in toluene at 110 °C followed by addition of
Yb(OTf)3 after 12 h furnished the benzofuran derivative 3aa in
38% yield. Similarly, formation of 4,7-dimethyl substituted
benzofuran 3ab was achieved in appreciable yield from 2,5-
dimethylphenol.
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DOI: 10.1039/C8CC10306B
Scheme 4. Synthetic applications.
To understand the plausible mechanism, few control
experiments were performed. 4-Phenyl-1-tosyl-1H-1,2,3-
triazole 1b and β-naphthol 2 was treated with Rh2(OAc)4 in
toluene at 110 °C in the absence of additive and oxygen.
Interestingly, formation of O-H insertion product 7 was
observed in 43% yield (Scheme 5).14 To further prove 7 as
potential intermediate, various conditions were screened
employing 7 as starting point. Treatment of 7 under the
optimized conditions afforded the 3k in 65% yield. Thermal
heating of 7 under nitrogen atmosphere in the absence of
both Rh- and Yb-catalysts did not afford the expected
transformation and 7 was recovered. Similar observations
were made when thermal heating of 7 at 110 °C under
nitrogen atmosphere in the presence of Rh- or Yb-catalysts as
well as thermal heating of 7 under oxygen atmosphere in the
absence of Rh- and Yb-catalysts. Next, reaction of 7 with
rhodium catalyst under oxygen atmosphere led to the
formation of 3k in 9% yield. On the other hand, 59% of 3k was
isolated when 7 was treated with Yb-catalyst under the oxygen
atmosphere. These experiments clearly suggested the
promising formation of insertion product 12 as potential
intermediate and importance of Yb(OTf)3 under O2 atmosphere
for the successive oxidative cyclization.
Scheme 3. Scope of β-naphthols and phenols. † Yb(OTf)3 was added after 3 h.
Next, to demonstrate the synthetic utility of the developed
method, we envisaged the conversion of naphthofurans to
biologically important polycyclic heteroaromatic compound.
For instance, construction of naphthofuroindole
4 was
achieved in 89% yield via copper-catalyzed C-N bond cross
coupling12 of ortho brominated naphthofuran 3o in the
presence of 5 mol % of CuI, 10 mol % of DMEDA, and K3PO4 at
70 °C in toluene (Scheme 4a). In addition, we successfully
established an unusual oxidative functionalization of 3a to
naphtho[2,1-b]furan-1(2H)-ones 513 in the presence of 10 mol
% of Pd(OAc)2, 1 equiv of Cu(OAc)2 in DMF at 100 °C for 12 h in
58% of yield (Scheme 4b). Reaction of naphthofuran 3s under
the similar conditions also furnished
6 in 47% yield,
demonstrating the general applicability of the oxidative
functionalization. Next, the one-pot conversion of alkyne to
naphthofuran was envisioned, since the CuTC was also
effective for the oxidative cyclization. Thus, the reaction of
phenylacetylene and mesylazide in presence of 10 mol% of
CuTC in toluene at room temperature for 3 h followed by
addition of β-naphthol 2a and Rh2(OAc)4 and heating reaction
mixture at 110 °C under oxygen atmosphere gave the product
3a in appreciable yield (Scheme 4c).
Scheme 5. Control experiments.
Based on the control experiments, we postulated the plausible
mechanism for the cascade Rh and Yb-catalyzed
transannulation of 1 with 2, which occurs in a sequential
manner. Reaction of active Rh(II) catalyst with 1 would form
reactive rhodium carbenoid I through the generation of
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3
Scheme 6. Plausible mechanism.
4
5
In conclusion, we have successfully developed a cascade Rh(II)
and Yb(III) catalysis for the transannulation of N-sulfonyl-1,2,3-
triazoles with substituted β-naphthol. The reaction involves
the initial rhodium catalyzed insertion of azavinyl carbene into
O-H bond followed by ytterbium catalyzed annulative C-C bond
formation and concomitant aerial oxidation. The developed
methodology tolerates various functional groups and offers
access to diverse substituted naphthofurans in moderate to
good yield. In addition, this methodology was successfully
extended to the synthesis of benzofurans employing phenols.
O-H inserted product, potential intermediate of the
transformation was isolated to postulate the possible
mechanism. Furthermore, the synthetic utility of this method
was demonstrated through the synthesis of polyhetero
aromatic system.
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We thank DST-SERB, New Delhi, India (Project No.
EMR/2016/003677/OC) for funding this work. SK and MK
thanks DST-SERB for the NPDF fellowship.
Conflicts of interest
“There are no conflicts to declare”.
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