CuI Mediated One-Pot Cycloacetalization/Ketalization of o-Carbonyl Allylbenzenes: Synthesis of Benzobicyclo[3.2.1]octane Core

Article abstract of DOI:10.1021/acs.orglett.7b00630

CuI/DMSO-mediated intramolecular cycloacetalization/ketalization of o-carbonyl allylbenzenes has been achieved for constructing [6,6,5]-tricycles having a ketal motif in good yields. The expeditious one-step route provides a three C-O bond formation. The key products with the structural framework of a benzofused dioxabicyclo[3.2.1]octane core have been confirmed by X-ray crystallographic analysis. Synthesis of dihydroisocoumarin has been studied.

Full text of DOI:10.1021/acs.orglett.7b00630

Letter
pubs.acs.org/OrgLett
CuI Mediated One-Pot Cycloacetalization/Ketalization of o‑Carbonyl
Allylbenzenes: Synthesis of Benzobicyclo[3.2.1]octane Core
Chieh-Kai Chan, Yu-Lin Tsai, and Meng-Yang Chang*
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
807, Taiwan
S
* Supporting Information
ABSTRACT: CuI/DMSO-mediated intramolecular cyclo-
acetalization/ketalization of o-carbonyl allylbenzenes has
been achieved for constructing [6,6,5]-tricycles having a ketal
motif in good yields. The expeditious one-step route provides
a three C−O bond formation. The key products with the
structural framework of a benzofused dioxabicyclo[3.2.1]octane core have been confirmed by X-ray crystallographic analysis.
Synthesis of dihydroisocoumarin has been studied.
Scheme 1. Retrosynthetic Route of
Benzobicyclo[3.2.1]octane
any structures having cyclic acetals or ketals have been
Mfound in various sources such as bioactive natural
products, functionalized materials, and diversified building
blocks.1 Among the reported molecules in the family, a core
structure having benzannulated acetals or ketals is relatively rare,
especially those with a dioxacyclic scaffold. For naturally
occurring products bearing this benzofused dioxabicycle core,
the representative frameworks include integrastatin A,2a
averufin,2b−d uroleuconaphins A2a,2e chloropreussomerin A,2f
and cystophloroketals E.2g Attracted by their challenging
frameworks, benzofused dioxabicycles have been the focus of
considerable attention in synthetic communities.3,4 A great deal
of effort has been devoted to benzofused acetals or ketals via
dihydroxylation and sequential acetalization or ketalization. In
general, dihydroxylative acetalization and ketalization have been
involved as two practical steps,5 including (1) transition-metal or
metal-free oxidant mediated dihydroxylation of functionalized
olefins and (2) acidic catalyst-promoted acetalization or
ketalization of the corresponding vicinal diols with carbonyl
compounds such as aldehydes or ketones.6 As a consequence,
numerous attempts have been devoted to the two-step
protection of carbonyl synthons. Therefore, a new single-vessel
route for simultaneous bond formation and ring construction is
an important challenge because a one-pot process can reduce
human effort, avoid chemical waste, and economize the cost and
reaction time.7 Furthermore, it allows for rapid and efficient
buildup of molecular complexity from relatively simple
substrates.
and isovanillin (1b) by a series of facile functional group
transformations, as summarized in Scheme 2.
Scheme 2. Synthesis of 2, 4, and 5
Continuing our research on synthetic applications of o-
carbonyl allylbenzenes,8 herein, we present a one-pot copper-
catalyzed synthesis of a benzofused bicyclo[3.2.1]octane core
from o-carbonyl allylbenzenes, as shown in Scheme 1. This
intramolecular one-pot cycloacetalization or -ketalization re-
action proceeds under mild conditions and affords the products
in high yields with high reaction efficiency. According to
preliminary results,8 three kinds of o-carbonyl allylbenzenes 2, 4,
and 5 were easily prepared from 3-hydroxybenzaldehyde (1a)
Received: March 1, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b00630
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Skeleton 2 shows synthesis via a three-step route which
includes (1) O-allylation (Z = H, Me, Ph), (2) Claisen
rearrangement (o-allyl and p-allyl), and (3) O-alkylation (R =
Me, iPr, nBu, cC5H9, Bn). To increase the substrate variants, the
o′-position of 1b was introduced with an aryl substituent to
provide biphenyls 3a−3o via NBS-mediated bromination and a
Suzuki−Miyaura cross-coupling. By use of similar three-step
routes, skeleton 4 (Ar = Ph, 2-MeC6H4, 3-MeC6H4, 4-MeC6H4,
2-MeOC6H4, 3-MeOC6H4, 4-MeOC6H4, 2-FC6H4, 3-FC6H4, 4-
FC6H4, 3-PhC6H4, 4-PhC6H4, 3,4-(MeO)2C6H3, 3,4,5-
(MeO)3C6H2) was generated. Furthermore, Grignard addition
of 2b and PCC-mediated oxidation of the resulting secondary
alcohols afforded skeleton 5. With skeletons 2, 4, and 5 in hand,
we commenced the study by treating 2a (1.0 mmol) with
Cu(OTf)2 (10 mol %) in DMSO (2 mL) as the medium at room
temperature for 10 h (Table 1, entry 1).9 Unfortunately, the
temperatures (80 → 120 → 150 °C) and elongating the reaction
times (10 → 15 h), the isolated yields of 6a were not improved
(74%, 66%, and 84%; entries 12−14). By the involvement of
TfOH (entry 15), no isolation of 6a was observed. Under a dry
nitrogen atmosphere (entry 16), the yield of 6a was maintained
(89%). From these observations, we concluded that 20 mol % of
CuI and 2 mL of DMSO provided optimal reaction conditions
(80 °C and 10 h) for one-pot cyclization.
On the basis of the experimental results, a plausible
mechanism for the formation of 6a is illustrated in Scheme 3.
Scheme 3. Plausible Mechanism
a
Table 1. Reaction Conditions
b
entry catalysts (mol %)
solvent
temp (°C) time (h) 6a (%)
c
1
Cu(OTf)2 (10)
Cu(OTf)2 (10)
Cu(OTf)2 (10)
Cu(OTf)2 (10)
Cu(OAc)2 (10)
CuSO4 (10)
CuF2 (10)
DMSO
DMSO
DMF
25
80
80
80
80
80
80
80
80
80
80
120
150
80
80
80
10
10
10
10
10
10
10
10
10
10
10
10
10
15
10
10
−
Initially, complexation of CuI with a terminal olefin of 2a yields
A. By intramolecular 6-exo-trig cyclization, B should be afforded
via the first C−O bond formation. Following the addition of B by
DMSO, C1 and C2 were generated via the second C−O bond
formation. However, the copper arm and DMSO side of C1
should be orientated as a trans-configuration such that the
occurrence of equilibrium between C1 and B is formed. Through
a cis-configured conformation of C2, an in situ generated iodide
group attacks the copper arm to lead to 6a by the intramolecular
bridged ring annulation (the third C−O bond formation).
Subsequently, CuI was regenerated and DMS was released.
Finally, construction of the benzobicyclo[3.2.1]octane core was
furnished via the cascade pathway of three C−O bond
formations.
2
36
c
3
−
−
c
4
MeNO2
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
5
28
17
10
80
54
88
90
74
66
84
6
7
8
CuI (10)
9
CuOTf (10)
CuI (15)
10
11
12
13
14
15
16
CuI (20)
CuI (20)
CuI (20)
CuI (20)
c
TfOH (20)
CuI (20)
−
With optimal conditions established (Table 1, entry 11) and
the plausible mechanism proposed (Scheme 3), CuI mediated
transformation from various o-carbonyl allylbenzenes 2, 4, and 5
to benzobicyclo[3.2.1]octanes 6−8 was examined next. As
shown in Scheme 4, we found that this methodology allowed
direct intramolecular cycloacetalization/ketalization of a broad
range of substrates under mild and neutral conditions using a
catalytic amount of CuI and a co-oxidant role of DMSO in good
to excellent yields. The efficient formation of 6a−6h illustrated
that the substituents (R and Z) on skeleton 2 did not affect the
yield changes (82%−90%). However, when 2i (Z = Ph) was
treated with CuI/DMSO, no detection of 6i was observed. Next,
we explored the scope of biphenyls as the reaction substrates. A
different aryl group of 4a−4o (for Ar, ortho-, meta-, para-
position; mono-, di-, trisubstituent) provided the desired 7a−o
in good to excellent yields (70%−86%) under the above
conditions. In particular, m-terphenyl 4k and p-terphenyl 4l
could be suitable substrates, affording 7k and 7l in 80% and 84%
yields, respectively. For the electronic nature of substituents, not
only electron-neutral but also electron-withdrawing and
electron-donating groups were appropriate. For the formation
of 7a−o, the scope of aryl groups was very broad. Moreover, this
reaction was found to not be limited to benzaldehydes as
substrates, and benzoketones 5a−h (Y = alkyl and aromatic
groups) also delivered 8a−8h in high yields (76%−86%). The
d
89
a
The reactions were run on a 1.0 mmol scale with 2a, solvent (2 mL),
b
c
d
dry air atmosphere. Isolated yields. No reaction. Dry nitrogen
atmosphere.
reaction was unsuccessful, and therefore, it was repeated under
heating at 80 °C (entry 2). Gratifyingly, the reaction at elevated
temperatures was completed in 10 h furnishing a mixture of
products from which the major product that was isolated in a
36% yield was identified as the expected 6a. The results
prompted us to optimize the reaction for improving the yield of
6a. The reactions were performed under DMF and MeNO2
conditions (entries 3−4); however, no yields of 6a were
provided. From the phenomenon, we understood that DMSO
performed the dual solvent and co-oxidant roles under a dry air
atmosphere.10
Next, some copper(II) complexes were studied, such as
Cu(OAc)2, CuSO4, and CuF2. However, none of them provided
higher yields of 6a than Cu(OTf)2 (entries 5−7). Changing the
Cu(II) to Cu(I) salts, CuI and CuOTf provided 80% and 54%
yields, respectively (entries 8−9). Furthermore, other catalytic
amounts (15 and 20 mol %) of CuI were examined; however, the
isolated yields only increased slightly to 88% and 90%,
respectively (entries 10−11). After elevating the reaction
B
DOI: 10.1021/acs.orglett.7b00630
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
ab
,
Scheme 4. Synthesis of 6−8
Scheme 6. Synthesis of 12
However, no further conversion was observed within 100 or 150
h due to the stereic hindrance of the ortho-aryl group. On the
other hand, benzoketal 8a could not be converted to the
dihydroisocoumarin since there was no occurrence of H-
abstraction.
a
All reactions were performed at 1.0 mmol scale with 2, 4, and 5.
Isolated yields.
b
In summary, we have developed a CuI/DMSO promoted one-
pot cycloacetalizaition or -ketalization of o-carbonyl allylben-
zenes 2, 4, and 5 at 80 °C for 10 h in good yields. The one-pot
process provides benzobicyclo[3.2.1]octanes 6−8 via a cascade
pathway of three C−O bond formations. The synthesis of
dihydroisocoumarins 12 has been studied. The related plausible
mechanisms have been proposed. The structures of the key
products were confirmed by X-ray crystallography. Further
investigations regarding the synthetic application of o-carbonyl
allylbenzenes will be conducted and published in due course.
structures of 7a, 8e, and 8g were determined by single-crystal X-
ray crystallography.11 Aside from the present one-pot cyclo-
acetalization or cycloketalization reaction, CuI/DMSO has also
been reported as a combination for cross-couplings,12a−k
iodinations,12l aminations,12m−p and tandem cyclizations.12q−t
By a one-pot two-step route (Suzuki−Miyaura coupling and our
method), simple benzobicyclo[3.2.1]octane 11 could be
obtained from o-formylphenyl boronic acids 9 in a 42% yield
via the formation of intermediate 10 (Scheme 5). Although the
isolated yield of 11 was low, it still provided a novel and efficient
transformation from o-formyl arylboronic acid to cyclic acetal.
ASSOCIATED CONTENT
* Supporting Information
■
S
Scheme 5. One-Step Synthesis of 11
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.7b00630.
Crystallographic data for 7a (CIF)
Crystallographic data for 8e (CIF)
Crystallographic data for 8g (CIF)
Crystallographic data for 12b (CIF)
Crystallographic data for 12d (CIF)
Detailed experimental procedures and spectroscopic data
for new compounds 6a−6h, 7a−7o, 8a−8h, 11, and 12a−
12h and X-ray analysis data of 7a, 8e, 8g, 12b, and 12d
(PDF)
As an extension of one-pot cycloacetalization/ketalization, the
reaction conditions were adjusted next (Scheme 6). To elongate
a 10-fold reaction time, dihydroisocoumarin 12 was isolated.13
Isocoumarins and dihydroisocoumarins possess diverse bio-
logical activities, such as antifungal, antiallergic, antimicrobial,
antiangiogenic, and antioxidant properities.13b,c,f Treatment of
6a−6h with CuI/DMSO provided 12a−12h in moderate yields.
After a longer reaction time (10 → 100 h), benzoacetal 6 was
slowly converted to dihydroisocoumarin 12. The structures of
12b and 12d were determined by single-crystal X-ray
crystallography.11 The proposed mechanism is shown in Scheme
6. Complexation of CuI with an oxygen atom of 6 yielded I. By
intramolecular C−O bond cleavage, II should be afforded.
Following the addition of II by DMSO, III was generated via a
new C−O bond formation. Finally, an in situ generated iodide
group attacked the copper arm to lead to 12 by an oxidative
process. Subsequently, CuI was regenerated and DMS was
released. To investigate the CuI/DMSO-mediated conversion
for biarylacetal skeleton 7, 7a was chosen as the model substrate.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: mychang@kmu.edu.tw.
ORCID
Meng-Yang Chang: 0000-0002-1983-8570
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors would like to thank the Ministry of Science and
Technology of the Republic of China for financial support
(MOST 105-2113-M-037-001).
C
DOI: 10.1021/acs.orglett.7b00630
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
2006, 45, 354−366. (g) Kirsch, S. F. Synthesis 2008, 2008, 3183−3204.
(h) Bur, S. K.; Padwa, A. Adv. Heterocycl. Chem. 2007, 94, 1−105.
(8) For synthetic applications of the o-carbonyl allylbenzenes by the
authors, see: (a) Chang, M.-Y.; Wu, M.-H.; Tai, H.-Y. Org. Lett. 2012, 14,
3936−3939. (b) Chang, M.-Y.; Wu, M.-H.; Chen, Y.-L. Org. Lett. 2013,
15, 2822−2825. (c) Chan, C.-K.; Tsai, Y.-L.; Chan, Y.-L.; Chang, M.-Y. J.
Org. Chem. 2016, 81, 9836−9847. (d) Chan, C.-K.; Chen, Y.-H.; Tsai,
Y.-L.; Chang, M.-Y. J. Org. Chem. 2017, 82, 3317−3326. (e) Chan, C.-K.;
Tsai, Y.-L.; Chang, M.-Y. Org. Lett. 2017, 19, 1358−1361.
(9) Metal triflates mediated synthesis by authors: for Sc(OTf)3, see:
(a) Chang, M.-Y.; Chen, Y.-C.; Chan, C.-K.; Huang, G. G. Tetrahedron
2015, 71, 2095. For Fe(OTf)3, see: (b) Chang, M.-Y.; Chen, Y.-H.;
Cheng, Y.-C. Tetrahedron 2016, 72, 518. For Bi(OTf)3, see: (c) Chang,
M.-Y.; Cheng, Y.-C.; Lu, Y.-J. Org. Lett. 2015, 17, 1264. (d) Chang, M.-
Y.; Cheng, Y.-C.; Lu, Y.-J. Org. Lett. 2015, 17, 3142. (e) Chang, M.-Y.;
Cheng, Y.-C. Org. Lett. 2015, 17, 5702. For In(OTf)3, see: (f) Chang,
M.-Y.; Lu, Y.-J.; Cheng, Y.-C. Tetrahedron 2015, 71, 6840. For
Cu(OTf)2, see: (g) Chan, C.-K.; Wang, H.-S.; Hsu, R.-T.; Chang, M.-Y.
Synthesis 2017, 49, in press (doi: 10.1055/s-0036-1589479).
(10) For recent reviews on applications of DMSO as a reagent, see:
(a) Wu, X.-F.; Natte, K. Adv. Synth. Catal. 2016, 358, 336−358.
(b) Jones-Mensah, E.; Karki, M.; Magolan, J. Synthesis 2016, 48, 1421−
1436.
(11) CCDC 1525582 (7a), 1525583 (8e), 1525584 (8g), 1525585
(12b), and 1525586 (12d) contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge via www.
ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12 Union
Road, Cambridge CB2 1EZ, U.K.; fax: 44-1223-336033; E-mail:
deposit@ccdc.cam.ac.uk).
(12) Selected examples on CuI/DMSO-mediated reactions: for cross-
coupling, see: (a) Xie, X.; Cai, G.; Ma, D. Org. Lett. 2005, 7, 4693−4695.
(b) Lu, B.; Ma, D. Org. Lett. 2006, 8, 6115−6118. (c) Fan, M.; Zhou, W.;
Jiang, Y.; Ma, D. Org. Lett. 2015, 17, 5934−5937. (d) Zhang, Y.; Yang,
X.; Yao, Q.; Ma, D. Org. Lett. 2012, 14, 3056−3059. (e) Chen, Y.; Wang,
Y.; Sun, Z.; Ma, D. Org. Lett. 2008, 10, 625−628. (f) Li, Z.; Sun, H.;
Jiang, H.; Liu, H. Org. Lett. 2008, 10, 3263−3266. (g) Ma, D.; Cai, Q.;
Zhang, H. Org. Lett. 2003, 5, 2453−2455. (h) Zhu, W.; Ma, D. J. Org.
Chem. 2005, 70, 2696−2700. (i) Zhu, W.; Ma, D. J. Org. Chem. 2005, 70,
2696−2700. (j) De Nonappa, P.; Pandurangan, K.; Maitra, U.; Wailes, S.
Org. Lett. 2007, 9, 2767−2770. (k) Fan, M.; Liu, Y.; Hu, Q.; Jia, L.; Chen,
Y. Eur. J. Org. Chem. 2016, 2016, 5470−5473. For iodination, see:
(l) Zhao, J.; Zhang, Q.; Liu, L.; He, Y.; Li, J.; Li, J.; Zhu, Q. Org. Lett.
2012, 14, 5362−5365. For amination, see: (m) Zhang, H.; Cai, Q.; Ma,
D. J. Org. Chem. 2005, 70, 5164−5173. (n) Jiang, L.; Lu, X.; Zhang, H.;
Jiang, Y.; Ma, D. J. Org. Chem. 2009, 74, 4542−4546. (o) Diao, X.; Wang,
Y.; Jiang, Y.; Ma, D. J. Org. Chem. 2009, 74, 7974−7977. (p) Fan, M.;
Zhou, W.; Jiang, Y.; Ma, D. Org. Lett. 2015, 17, 5934−5937. For tandem
cyclization, see: (q) Ouyang, H.-C.; Tang, R.-Y.; Zhong, P.; Zhang, X.-
G.; Li, J.-H. J. Org. Chem. 2011, 76, 223−228. (r) Vallerotto, S.; Le
Douaron, G.; Bernadat, G.; Ferrie, L.; Figadere, B. Synthesis 2016, 48,
3232−3240. (s) Li, L.; Wang, M.; Zhang, X.; Jiang, Y.; Ma, D. Org. Lett.
2009, 11, 1309−1312. (t) do Nascimento, J. E. R.; Goncalves, L. C. C.;
Hooyberghs, G.; van der Eycken, E. V.; Alves, D.; Lenardao, E. J.; Perin,
G.; Jacob, R. G. Tetrahedron Lett. 2016, 57, 4885−4889.
REFERENCES
■
(1) Magdziak, D.; Meek, S. J.; Pettus, T. R. R. Chem. Rev. 2004, 104,
1383−1430.
(2) For integrastatin A, see: (a) Singh, S. B.; Zink, D. L.; Quamina, D.
S.; Pelaez, F.; Teran, A.; Felock, P.; Hazuda, D. J. Tetrahedron Lett. 2002,
43, 2351−2354. For averufin, see: (b) Holker, J. S. E.; Kagal, S. A.;
Mulheirn, L. J.; White, P. M. Chem. Commun. 1966, 911b−913b.
(c) Roffey, P.; Sargent, M. V. Chem. Commun. 1966, 913−914.
(d) Grandjean, J. J. Chem. Soc. D 1971, 1060a. For uroleuconaphins A2a,
see: (e) Horikawa, M.; Tanaka, M.; Kaku, H.; Nishii, T.; Tsunoda, T.
Tetrahedron 2008, 64, 5515−5518. For chloropreussomerin A, see:
(f) Chen, S.; Chen, D.; Cai, R.; Cui, H.; Long, Y.; Lu, Y.; Li, C.; She, Z. J.
Nat. Prod. 2016, 79, 2397−2402. For cystophloroketals E, see: (g) El
Hattab, M.; Genta-Jouve, G.; Bouzidi, N.; Ortalo-Magne, A.; Hellio, C.;
Marechal, J.-P.; Piovetti, L.; Thomas, O. P.; Culioli, G. J. Nat. Prod. 2015,
78, 1663−1670.
(3) Examples of one-pot construction of benzofused dioxabicycle: for
Pd2+, see: (a) Li, Q.; Jiang, X.; Fu, C.; Ma, S. Org. Lett. 2011, 13, 466−
469. For photolysis, see: (b) Streit, U.; Birbaum, F.; Quattropani, A.;
Bochet, C. G. J. Org. Chem. 2013, 78, 6890−6910. (c) Nishio, T.;
Sakurai, N.; Iba, K.; Hamano, Y.-I.; Sakamoto, M. Helv. Chim. Acta 2005,
88, 2603−2609. (d) Lehmann, T. E.; Mueller, G.; Berkessel, A. J. Org.
Chem. 2000, 65, 2508−2516. For oxidant, see: (e) Thompson, H. W.;
Rashid, S. Y. J. Org. Chem. 2002, 67, 2813−2825. For electrochemical
oxidation, see: (f) Christensen, L.; Miller, L. L. J. Org. Chem. 1981, 46,
4876−4880.
(4) For the synthesis of benzofused dioxabicycles, see: (a) Foot, J. S.;
Giblin, C. M. P.; Taylor, R. J. K. Org. Lett. 2003, 5, 4441−4444. (b) Foot,
J. S.; Giblin, G. M. P.; Whitwood, A. C.; Taylor, R. J. K. Org. Biomol.
Chem. 2005, 3, 756−763. (c) Cayley, A. N.; Gallagher, K. A.; Menard-
Moyon, C.; Schmidt, J. P.; Diorazio, L. J.; Taylor, R. J. K. Synthesis 2008,
2008, 3846−3856. (d) Mal, J.; Nath, A.; Venkateswaran, R. V. J. Org.
Chem. 1996, 61, 9164−9167. (e) Ramana, C. V.; Reddy, C. N.;
Gonnade, R. G. Chem. Commun. 2008, 3151−3153. (f) More, A. A.;
Ramana, C. V. Org. Lett. 2016, 18, 612−615. (g) Tadross, P. M.; Bugga,
P.; Stoltz, B. M. Org. Biomol. Chem. 2011, 9, 5354−5357. (h) Green, J.
C.; Brown, E. R.; Pettus, T. R. R. Org. Lett. 2012, 14, 2929−2931.
(i) Kim, I.; Kim, S. G.; Choi, J.; Lee, G. H. Tetrahedron 2008, 64, 664−
671. (j) Ullah, E.; Rotzoll, S.; Schmidt, A.; Michalik, D.; Langer, P.
Tetrahedron Lett. 2005, 46, 8997−8999. (k) Srinivas, V.; Koketsu, M. J.
Org. Chem. 2013, 78, 11612−11617. (l) Yin, G.; Ren, T.; Rao, Y.; Zhou,
Y.; Li, Z.; Shu, W.; Wu, A. J. Org. Chem. 2013, 78, 3132−3141.
(m) Gueney, M.; Dastan, A.; Balci, M. Helv. Chim. Acta 2005, 88, 830−
838. (n) Aiguade, J.; Hao, J.; Forsyth, C. J. Org. Lett. 2001, 3, 979−982.
(o) Cho, Y. S.; Kim, H. Y.; Cha, J. H.; Pae, A. N.; Koh, H. Y.; Choi, J. H.;
Chang, M. H. Org. Lett. 2002, 4, 2025−2028. (p) Francisco, C. G.;
Freire, R.; Herrera, A. J.; Martin, I. P.; Suarez, E. Org. Lett. 2002, 4,
1959−1961. (q) Oikawa, M.; Uehara, T.; Iwayama, T.; Sasaki, M. Org.
Lett. 2006, 8, 3943−3946. (r) Harada, H.; Matsushita, Y.; Yodo, M.;
Nakamura, M.; Yonetani, Y. Chem. Pharm. Bull. 1987, 35, 3215−3226.
(5) (a) Wuts, P. G. M.; Greene, T. Protective Groups in Organic
Synthesis; John Wiley & Sons: New York, 2006. (b) Yu, M.; Pagenkopf,
B. L. Tetrahedron 2003, 59, 2765−2771.
(13) Selected examples on isolation, synthesis, and bioligical activities
of dihydroisocoumarins: (a) Salvadori, P.; Superchi, S.; Minutolo, F. J.
Org. Chem. 1996, 61, 4190−4191. (b) Superchi, S.; Pini, D.; Salvadori,
P.; Marinelli, F.; Rainaldi, G.; Zanelli, U.; Nuti-Ronchi, V. Chem. Res.
Toxicol. 1993, 6, 46−49. (c) Guimaraes, K. G.; de Freitas, R. P.; Ruiz, A.
L. T. G.; Fioroto, G. F.; de Garvalho, J. E.; da Cunha, E. F. F.; Ramalho,
T. C.; Alves, R. B. Eur. J. Med. Chem. 2016, 111, 103−113 and references
cited therein. (d) Guimaraes, K. G.; de Souza Filho, J.; dos Mares-Guia,
T. R.; Braga, F. G. Phytochemistry 2008, 69, 439−444. (e) Endringer, D.
C.; Guimaraes, K. G.; Kondratyuk, T. P.; Pezzuto, J. M.; Braga, F. C. J.
Nat. Prod. 2008, 71, 1082−1084. (f) Hampl, V.; Wetzel, I.; Bracher, F.;
Krauss, J. Sci. Pharm. 2011, 79, 21−30.
(6) Examples of the intramolecular diol protection: (a) Uno, H.;
Masumoto, A.; Honda, E.; Nagamachi, Y.; Yamaoka, Y.; Ono, N. J.
Chem. Soc., Perkin Trans. 1 2001, 3189−3197. (b) Chang, M.-Y.; Wu,
M.-H.; Lee, N.-C.; Lee, M.-F. Tetrahedron Lett. 2012, 53, 2125−2128.
(c) Harada, H.; Matsushita, Y.; Yodo, M.; Nakamura, M.; Yonetani, Y.
Chem. Pharm. Bull. 1987, 35, 3215−3226. (d) Thompson, H. W.;
Rashid, S. Y. J. Org. Chem. 2002, 67, 2813−2825. (e) Kolb, H. C.; van
Nieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483−2547.
(7) (a) Tietze, L. F., Brasche, G., Gericke, K., Eds. Domino Reactions in
Organic Synthesis; Wiley-VCH, Verlag GmbH & Co: Weinheim,
Germany, 2006. (b) Nicolaou, K. C.; Chen, J. S. Chem. Soc. Rev. 2009,
38, 2993−3009. (c) Enders, D.; Grondal, C.; Huttl, M. R. M. Angew.
Chem., Int. Ed. 2007, 46, 1570−1581. (d) Hussain, M. M.; Walsh, P. J.
Acc. Chem. Res. 2008, 41, 883−893. (e) Sun, X. L.; Tang, Y. Acc. Chem.
Res. 2008, 41, 937−948. (f) Guo, H.-C.; Ma, J.-A. Angew. Chem., Int. Ed.
D
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