Rh(iii)-catalyzed [5+1] oxidative cycloaddition of arylguanidines with alkynes: a novel access to C4-disubstituted 1,4-dihydroquinazolin-2-amines

Article abstract of DOI:10.1039/c5cc06388d

A novel and mild Rh^III-catalyzed [5+1] oxidative cycloaddition between arylguanidines and alkynes efficiently affords C4-disubstituted 1,4-dihydroquinazolin-2-amines. Members of this family of heterocycles, which contain the relevant cyclic guanidine units, have shown interesting pharmacological properties. The mechanism probably involves the formation of an eight-membered rhodacycle in which the imine unit of guanidine is coordinated to the Rh center. This rhodacycle would evolve to give the C-4 disubstituted 1,4-dihydroquinazolin-2-amine skeleton.

Full text of DOI:10.1039/c5cc06388d

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DOI: 10.1039/C5CC06388D
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COMMUNICATION
Rh(III)-Catalyzed [5+1] Oxidative Cycloaddition of Arylguanidines
with Alkynes: A Novel Access to C4-Disubstituted 1,4-
Dihydroquinazolin-2-amines
Received 00th January 20xx,
Accepted 00th January 20xx
Ana Cajaraville, Jaime Suárez, Susana López, Jesús A. Varela and Carlos Saá*
DOI: 10.1039/x0xx00000x
www.rsc.org/
The novel and mild RhIII-catalyzed [5+1] oxidative cycloaddition On the other hand, [4+1] and [5+1] oxidative cycloadditions of
between arylguanidines and alkynes efficiently affords C4- oxygenated substrates with allenes8 and enynes9 have been
disubstituted 1,4-dihydroquinazolin-2-amines. Members of this recently described.
family of heterocycles, which contain the relevant cyclic guanidine
units, have shown interesting pharmacological properties. The
mechanism probably involves the formation of an eight-
membered rhodacycle in which the imine unit of the guanidine is
coordinated to the Rh center. This rhodacycle would evolve to
give the C-4 disubstituted 1,4-dihydroquinazolin-2-amine skeleton.
Benzofused nitrogenated heterocycles are privileged structural
units that are found in many natural products and
pharmaceuticals with important physiological and biological
activities.1 In the last few decades, the most common synthetic
methods for the preparation of these compounds have relied
on transition metal-catalyzed processes.2 In this regard,
Scheme 1 Azaheterocycles by Metal-Catalyzed Oxidative Cycloadditions.
directed C–H activation towards the formation of C–C and C–N
bonds has received the most attention owing to its sustainable
and environmentally benign features.3 For dehydrogenative N–
H/C–H coupling processes, besides oxidative annulations4
(intramolecular processes with the formation of C–N bonds),
typical [n+2] oxidative cycloadditions5 of monofunctionalized
substrates (n atoms = 3, 4, 5) with unsaturated two-carbon
partners, e.g. alkynes, provide an easy entry to a wide variety
of azaheterocycles such as indoles ([3+2]), isoquinolines and
isoquinolones ([4+2]), benzazepines ([5+2]) (Scheme 1, eq 1).
Similar metal-catalyzed C–H activation strategies have also
proven reliable for the formation of the corresponding
benzofused dinitrogenated heterocycles bearing N–N bonds.6
Alkynes can also participate in more unusual [n+1] oxidative
cycloadditions. Thus, isoindolines were obtained by Rh-
catalyzed [4+1] oxidative cycloaddition of primary
benzylamines with internal aliphatic alkynes (Scheme 1, eq 2).7
However, to our knowledge, [5+1] oxidative cycloadditions of
di(tri)nitrogenated substrates with alkynes are unknown.
Herein, we report the novel Rh(III)-catalyzed [5+1] oxidative
cycloaddition of arylguanidines with alkynes to give C-4
disubstituted 1,4-dihydroquinazolin-2-amines containing the
guanidine moiety, interesting structural motif present in many
bioactive compounds (Scheme 1, eq 3).10
We began our investigation by examining the reaction
between N,N'-dimethyl-N,N'-diphenylguanidine 1a11 and 3-
hexyne 2a under our previously reported conditions:12 t-AmOH
at 60 °C under argon, using [Cp*RhCl2]2 (2.5 mol %) and
.
Cu(OAc)2 H2O (2.1 equiv) as the oxidant (Table 1). Only traces
of the six-membered 1,4-dihydroquinazolin-2-amine 3a were
observed by GCMS (entry 1). Pleasingly, replacement of the
oxidant Cu(OAc)2.H2O by AgOAc gave 3a in 73% yield on using
an air atmosphere (entry 2). This new oxidative cycloaddition
strongly depends on the choice of solvent.13 To our delight, the
use of protic solvents such as i-PrOH was beneficial to the
reaction and gave 3a in an excellent 91% yield (entry 3).
Control experiments showed that both [Cp*RhCl2]2 and AgOAc
were necessary as the reaction failed in their absence (entries
4 and 5). The third row catalyst [Cp*IrCl2]2 or other oxidants
This journal is © The Royal Society of Chemistry 20xx
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like O2, AgOPiv and AgOCOCF3 gave low-to-moderate yields of butyne 2d (R3 = R4 = Me), was less effective and VgiaewveArttichleeO1nl,i4ne-
3a (entries 6-9).13 Interestingly, both the reaction with a lower dihydroquinazolin-2-amine 3ad in moderate yield.
DOI: 10.1039/C5CC06388D
concentration of 1a and a scaled-up process gave fairly good
yields of 1,4-dihydroquinazolin-2-amine 3a (entries 10–11).
Table
2
RhIII-Catalyzed [5+1] Oxidative Cycloaddition of p- and m-Substituted
Arylguanidines 1b–h and 3-Hexyne 2a to 1,4-Dihydroquinazolin-2-amines 3b–h. a,b
Table 1 Reaction Optimization.a
Yield of 3a
Entry
Oxidant
Additive
Solvent
(%)b
trace
73
1c
2
Cu(OAc)2.H2O
AgOAc
AgOAc
AgOAc
-
AgOAc
O2
Ag(OPiv)
Ag(O2CCF3)
AgOAc
AgOAc
AgSbF6
tAmOH
tAmOH
iPrOH
iPrOH
iPrOH
iPrOH
tAmOH
iPrOH
tAmOH
iPrOH
iPrOH
-
-
-
3
91
-
-
trace
39
51
trace
86
70
4d
5e
6f
Na2CO3
-
a
7g
8
Na2CO3
Optimized conditions: 1, 0.4 mmol; 2a, 0.4 mmol; [1] = 0.2 M in i-PrOH (2 mL);
60 °C, air, 8 h. b Isolated yields. c Conditions: 40 °C, 8 h. d Indole 4e (19%) was also
-
-
-
-
isolated.13
9
Functionalized aliphatic alkynes were analyzed next.15 Symmetrical
α,ω-enyne 2e gave the C-4 disubstituted 1,4-dihydroquinazolin-2-
amine 3ae, which contains three double bonds susceptible to
further manipulation. Notably, 1,3-enynes 2f and 2g reacted
smoothly to give the C-4 difunctionalized 1,4-dihydroquinazolin-2-
amines 3af and 3ag as single regioisomers in 76% and 62% yield.16
Gratifyingly, alkynyl 1,4-diols were also well tolerated by the
10h
11i
a Conditions: 1a, 0.4 mmol; 2a, 0.4 mmol; [1a] = 0.2 M. b Isolated yields. c Under
d
e
f
an argon atmosphere. No catalyst was used. No AgOAc was used. Catalyst:
h
[Cp*IrCl2]2 (2.5 mol%). g AgOAc (25 mol%). [1a] = 0.037 M. i Conditions: 1a, 1.3
mmol; 2a, 1.3 mmol; [1a] = 0.2 M.
Once the conditions had been optimized, we proceeded to
evaluate the scope and limitations of both partners in the
oxidative cycloaddition reaction. Gratifyingly, para- and meta-
substituted aryl guanidines 1b–h were well tolerated and they
afforded 1,4-dihydroquinazolin-2-amines 3b–h in moderate-to-
good yields (Table 2).14 The electronic properties of the para-
substituted aryl guanidines had a significant effect on the
reaction. Thus, the moderate electron-donating methyl group
provided the stable 1,4-dihydroquinazolin-2-amine 3b in 94%
yield while the highly electron-donating methoxy group
afforded the unstable 1,4-dihydroquinazolin-2-amine 3c in a
moderate 45% yield. By contrast, electron-poor substituents
on aryl guanidines, e.g., chloro 1d and methoxycarbonyl 1e,
gave low-to-moderate yields of the corresponding 1,4-
dihydroquinazolin-2-amines 3d,e.13 Interestingly, reaction of
the meta-substituted arylguanidines was completely
regioselective through activation of the less-hindered C–H
bond, affording the 1,4-dihydroquinazolin-2-amines 3f–h in
moderate-to-good yields. Note that the electronic properties
of the substituents at the meta-position of the arylguanidine
did not have an appreciable effect on the reaction yield. Thus,
either electron-releasing or electron-withdrawing groups in
arylguanidines 1f,h provided the corresponding 1,4-
dihydroquinazolin-2-amines 3f,h in similar yields.
reaction conditions, thus providing
a one-pot synthesis of
interesting functionalized spiro-1,4-dihydroquinazolin-2-amines 3ah
and 3ai (as an 8.5:1 diastereoisomeric mixture), thereby making this
one-carbon oxidative annulation protocol attractive to medicinal
chemistry.17
In an effort to gain an insight into the reaction mechanism, several
experiments to form the cyclometalated rhodium complexes were
conducted. The new six-membered cyclometalated Rh(III) complex
5a was isolated in 81% yield by reacting [Cp*RhCl2]2 with 2.2
equivalents of guanidine 1a in MeOH at rt for 2 h (Scheme 2, eq 1).
The structure of 5a was characterized by X-ray crystallography18 and
by NMR spectroscopy.13 Gratifyingly, further reaction of 5a with 2a
(1.2 equiv) at room temperature led to the quantitative formation
of air-stable complex 6a in 5 min (Scheme 2, eq 2). The X-ray
structure of 6a confirmed a characteristic eight-ring boat structure
(torsion angle C(1)-C(2)-C(21)-C(22) = 60.5°) in which the RhCp*
fragment displays
a three-legged piano stool environment
completed by the imino NH group of the guanidine and the C atom
of the vinyl moiety. The Rh(1)-N(10) and Rh(1)-C(22) bond lengths
of 2.092(5) and 2.060(6) Å, respectively, compare well with those
found in other rhodium cyclometalated complexes reported by
Jones,19 and support the dative and single character of the bonds.
Both chloro-complexes 5a and 6a were quantitatively transformed
into the corresponding acetate derivatives 5b and 6b by treatment
with AgOAc (1 equiv) in dichloromethane.
To our delight, a stoichiometric experiment using complex 6b in
iPrOH/AcOH showed the presence of two reaction products, the
major quinazoline 3a and the minor styrene 7a, the latter probably
derived from protonolysis of complex 6b (Scheme 3).20
We proceeded to examine the oxidative cycloaddition of aryl
guanidines 1a and 1f with several alkynes 2 (Table 3). The
symmetrically substituted aliphatic alkynes with long chains, 4-
octyne 2b (R3 = R4 = n-Pr) and 2c (R3 = R4 = n-Bu) gave the
corresponding 1,4-dihydroquinazolin-2-amines 3ab, 3fb and
3ac in fairly good yields, whereas the parent internal alkyne, 2-
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coordination of the guanidine to the catalytically active
Cp*Rh(OAc)2 I followed by ortho C–H bond activation
Table 3 Rh-Catalyzed [5+1] Oxidative Cyclization of Arylguanidine 1a with Substituted
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DOI: 10.1039/C5CC06388D
Aliphatic Alkynes.a
generates a six-membered rhodacycle 5b. Coordination and
insertion of the alkyne 2 into the Rh–C bond of 5b gives a new
eight-membered rhodacycle 6.22 β-hydride elimination with
concomitant loss of AcOH23 followed by protonolysis at central
carbon of the transient allene formed24 would afford π-
allylrhodium intermediate II.25 Finally, nucleophilic attack by
the imine at the more electrophilic position of II delivers the
C4-disubstituted-1,4-dihydroquinazolin-2-amine 326 and
a
Cp*RhI species, which is reoxidized by silver acetate under air
to the next catalytic cycle.
Scheme 3 Proposed Catalytic Cycle.
a Optimized conditions: 1, 0.4 mmol; 2a, 0.4 mmol; [1] = 0.2 M in i-PrOH (2 mL);
60 °C, Air, 8 h. b Conditions: 40 °C in a sealed tube, 24 h. c AgOAc: 4 eq.
After heating styrene 7a under the typical catalytic conditions
for 24h was recovered unchanged, which suggests that is a
side product instead of a reaction intermediate. In addition,
quinazoline 3a-d, which is deuterated at the vinylic position
(66% D incorporation), was obtained when the catalytic
reaction of arylguanidine 1a and alkyne 2a was performed in
deuterated isopropanol (Scheme 2, eq 3).13
Scheme 2 Mechanistic Studies.
Conclusions
In summary, we have successfully developed a new and
efficient rhodium-catalyzed [5+1] oxidative cycloaddition
between guanidines and internal aliphatic alkynes to give C-4
disubstituted 1,4-dihydroquinazolin-2-amines. The reaction
tolerates a wide range of functional groups in both the
guanidine and alkyne partners, and provides an easy access to
relevant functionalized heterocycles containing the guanidine
moiety. Further mechanistic studies and investigations on the
application of this novel oxidative cycloaddition are currently
underway in our laboratory.
Acknowledgements
This work was supported by MICINN (project CTQ2011-28258),
Xunta de Galicia and European Regional Development Fund
(projects GRC2014/032 and EM 2012/051). A. C. and J. S. thank
Spanish MICINN and Xunta de Galicia for a predoctoral FPI
fellowship and postdoctoral contract, respectively.
a Diamond plots of the structures of complexes 5a and 6a in the crystal with
ellipsoids at 30% probability and the Cp* methyl groups omitted for clarity.
On the basis of the above results and previous reports,21
a
tentative reaction mechanism for the Rh(III)-catalyzed [5+1]
oxidative cycloaddition is shown in Scheme 3. Initial
Notes and references
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1
2
3
(a) A. R. Katrizky, C. W. Rees and E. F. V. Scriven, in
Comprehensive Heterocyclic Chemistry II, Eds.; Elsevier,
1996; (b) J. J. Li, in Heterocyclic Chemistry in Drug Discovery;
Wiley, 2013; (c) E. Vitaku, D. T. Smith and J. T. Njardarson, J.
Med. Chem., 2014, 57, 10257.
(a) G. Zeni and R. C. Larock, Chem. Rev., 2006, 106, 4644; (b)
J. P. Wolfe, Synthesis of Heterocycles via Metal-Catalyzed
Reactions that Generate One or More Carbon-Heteroatom
DOI: 10.1021/acs.orglett.5b01986; (c) W. Miura, K. Hirano
and M. Miura, Org. Lett. DOI: 10.1021D/aOcIs: .1o0r.1g0le39Vtit/eC.w55bACr0tCi1c0l9e64O308nl8.inDe
(a) P. Gandeepan, P. Rajamalli and C.-H. Cheng, Chem. Eur. J.,
2015, 21, 9198; (b) N. Casanova, N., A. Seoane, J. L.
Mascareñas and M. Gulías, Angew. Chem., Int. Ed., 2015, 54,
2374.
8
9
D. J. Burns and H. W. Lam, Angew. Chem., Int. Ed., 2014, 53,
9931.
Bonds; Springer: Berlin, 2013; (c) Y. Yamamoto, Chem. Soc. 10 (a) F. Rodriguez, I. Rozas, J. E. Ortega, A. M. Erdozain, J. J.
Rev., 2014, 43, 1575.
Meana and L. F. Callado, J. Med. Chem., 2008, 51, 3304; (b)
A. Coqueiro, L. O. Regasini, P. Stapleton, V. da Silva and S.
Gibbons, J. Nat. Prod., 2014, 77, 1972; (c) R. D. Espirito
Santo, M. G. M. Machado, J. L. dos Santos, E. R. P. Gonzalez
and C. M. Chin, Curr. Org. Chem., 2014, 18, 2572; (d) B. Kelly,
M. McMullan, C. Muguruza, J. E. Ortega, J. J. Meana, L. F.
Callado and I. Rozas, J. Med. Chem., 2015, 58, 963.
For recent reviews on directing-group promoted metal-
catalyzed C–H activation, see: (a) K. M. Engle, T.-S. Mei, M.
Wasa and J.-Q. Yu, Acc. Chem. Res., 2011, 45, 788; (b) P. B.
Arockiam, C. Bruneau and P. H. Dixneuf, Chem. Rev., 2012,
112, 5879; (c) N. Kuhl, M. N. Hopkinson, J. Wencel-Delord
and F. Glorius, Angew. Chem., Int. Ed., 2012, 51, 10236; (d) D.
A. Colby, A. S. Tsai, R. G. Bergman and J. A. Ellman, Acc. 11 Arylguanidines were synthesized from commercially
Chem. Res., 2012, 45, 814; (e) G. Rouquet and N. Chatani,
Angew. Chem., Int. Ed., 2013, 52, 11726; (f) G. Shi and Y.
available N-methylanilines and N-methyl-N-arylcyanamides.
See Supporting Information for details.
Zhang, Adv. Synth. Catal., 2014, 356, 1419; (g) N. Kuhl, N. 12 A. Cajaraville, S. López, J. A. Varela and C. Saá, Org. Lett.,
Schröder and F. Glorius, Adv. Synth. Catal., 2014, 356, 1443;
2013, 15, 4576.
(h) S. De Sakar, W. Liu, S. I. Kozhushkov and L. Ackermann, 13 See Supporting Information for details.
Adv. Synth. Catal., 2014, 356, 1461; (i) M. Zhang, Y. Zhang, X. 14 Ortho-substituted arylguanidines remained unchanged.
Jie, H. Zhao, G. Li and W. Su, Org. Chem. Front., 2014, 1, 843; 15 Diaryl and unsymmetrical alkyl arylalkyne partners did not
(j) G. Qiu, Y. Kuang and J. Wu, Adv. Synth. Catal., 2014, 356,
3483; (k) X-X. Guo, D-W. Gu, Z. Wu and W. Zhang, Chem.
participate in the [5+1] cycloaddition, only traces of indoles
are isolated. See Supporting Information for details.
Rev., 2015, 115, 1622; For a recent review on oxidant-free C– 16 Arylguanidine 1a remains unreactive under the acidic Lam’s
H bond functionalizations, see: (l) J. Mo, L. Wang, Y. Liu and
X. Cui, Synthesis, 2015, 47, 439.
conditions, [{Cp*RhCl2}2] (2.5 mol%), Cu(OAc)2 (2.1 equiv.),
AcOH (0.1 equiv.), dioxane, 60 °C. See ref 9.
4
5
(a) T-S. Mei, X. Wang and J-Q. Yu, J. Am. Chem. Soc., 2009, 17 For bioactive spirodihydroquinazolines, see: (a) A. C. Tinker,
131, 10806; (b) W. C. P. Tsang, N. Zheng and S. L. Buchwald,
J. Am. Chem. Soc., 2005, 127, 14560; (c) K. Takamatsu, K.
Hirano, T. Satoh and M. Miura, Org. Lett., 2014, 16, 2892; (d)
W. Zhou, Y. Liu, Y. Yang and G-J. Deng, Chem. Commun.,
2012, 48, 10678; (e) P-C. Huang, K. Parthasarathy and C-H.
Cheng, Chem. Eur. J., 2013, 19, 460.
H. G. Beaton, N. Boughton-Smith, T. R. Cook, S. L. Cooper, L.
Fraser-Rae, K. Hallam, P. Hamley, T. McInally, D. J. Nicholls,
A. D. Pimm and A. V. Wallace, J. Med. Chem., 2003, 46, 913;
(b) D. Rambabu, S. K. Kumar, B. Y. Sreenivas, S. Sandra, A.
Kandale, P. Misra, M. V.B. Rao and M. Pal, Tetrahedron Lett.,
2013, 54, 495.
For indoles: (a) D. R. Stuart, M. Bertrand-Laperle, K. M. N. 18 CCDC 1053853 (5a) and 1053854 (6a) contain the
Burgess and K. Fagnou, J. Am. Chem. Soc., 2008, 130, 16474-
16475. (b) D. R. Stuart, P. Alsabeh, M. Kuhn and K. Fagnou, J.
Am. Chem. Soc., 2010, 132, 18326; (c) L. Ackermann and A. V.
Lygin, Org. Lett., 2012, 14, 764; (d) X. Zhang, W. Si, M. Bao,
supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/data_request/cif.
N. Asao, Y. Yamamoto and T. Jin, Org. Lett., 2014, 16, 4830; 19 (a) L. Li, W. W. Brennessel and W. D. Jones, J. Am. Chem.
(e) G. Zhang, H. Yu, G. Qin and H. Huang, Chem. Commun.,
2014, 50, 4331; For isoquinolines: (f) N. Guimond and K.
Soc., 2008, 130, 12414; (b) L. Li, W. W. Brennessel and W. D.
Jones, Organometallics, 2009, 28, 3492.
Fagnou, J. Am. Chem. Soc., 2009, 131, 12050; (g) K. 20 Styrene 7a was not observed when the reaction was
Morimoto, K. Hirano, T. Satoh and M. Miura, Org. Lett.,
performed using complex 6b as catalyst.
2010, 12, 2068; (h) D-S. Kim, J-W. Park and C-H. Jun, Adv. 21 G. Li, Z. Ding and B. Xu, Org. Lett., 2012, 14, 5338.
Synth. Catal., 2013, 355, 2667; (i) J. Li, M. John and L. 22 The regioselectivity with unsymmetrically substituted
Ackermann, Chem. Eur. J., 2014, 20, 5403; For isoquinolones:
(j) T. K. Hyster and T. Rovis, J. Am. Chem. Soc., 2010, 132,
10565; (k) G. Song, D. Chen, C-L. Pan, R. H. Crabtree and X. Li,
J. Org. Chem., 2010, 75, 7487; (l) L. Ackermann, A. V. Lygin
and N. Hofmann, Angew. Chem., Int. Ed., 2011, 50, 6379; (m)
H. Zhong, D. Yang, S. Wang and J. Huang, Chem. Commun.,
2012, 48, 3236; For benzazepines: (n) L. Wang, J. Huang, S.
Peng, H. Liu, X. Jiang and J. Wang, Angew. Chem., Int. Ed.,
2013, 52, 1768.
alkynes seems to be mainly derived from the insertion of the
- +
δ δ
polarized triple bond into the complementary Ar ―Rh bond
(see ref. 5b). Thus, in the case of enynes 2f and 2g, the
alkenyl substituent will be located α to the Rh during the
formation of rhodacycle 6. In the case of alkyl arylalkynes, no
[5+1] adduct is observed due to the favored formation of
rhodacycle 6 in which the phenyl is located α to the Rh and,
therefore, lacks the necessary allylic hydrogens to evolve.
23 R. Zeng, S. Wu, C. Fu and S. Ma J. Am. Chem. Soc., 2013, 135,
18284.
6
7
(a) K. Inamoto, T. Saito, M. Katsuno, T. Sakamoto and K.
Hiroya, Org. Lett., 2007, 9, 2931; (b) X. Li, L. He, H. Chen, W. 24 No Rh-H signals could be detected during the monitorization
Wu and H. Jiang, J. Org. Chem., 2013, 78, 3636; (c) W. Yang,
J. Chen, X. Huang, J. Ding, M. Liu and H. Wu, Org. Lett., 2014, 25 π-Allylrhodium intermediates have also been proposed by
16, 5418; (d) L. Xing, Z. Fan, C. Hou, G. Yong and A. Zhang,
Lam in a related process with enynes (ref 9).
Adv. Synth. Catal., 2014, 356, 972.(e) G. Brasche and S. L. 26 (a) With enynes 2f and 2g, rhodacycles 6 would undergo
Buchwald, Angew. Chem., Int. Ed., 2008, 47, 1932.
(a) K. Morimoto, K. Hirano, T. Satoh and M. Miura, Chem.
Lett., 2011, 40, 600; for other [4+1] oxidative cycloadditions,
see: (b) K. Takamatsu, K. Hirano and M. Miura, Org. Lett.
by 1H NMR experiments.
[1,4]-H migrations to form intermediates II (see ref. 9). (b)
With alkynyl-1,4-diols 2h and 2i as partners, tautomerization
to the aldehyde (of the initial enol formed) followed by
hemiacetalization (3ai) and oxidation to the lactone (3ah) is
observed.
4 | J. Name., 2012, 00, 1-3
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