Synthesis of benzoxazoles via an amine-catalyzed [4 + 1] annulation

Article abstract of DOI:10.1021/ol400988e

An unprecedented simple pyrrolidine catalyzed [4 + 1] annulation reaction of ynals with N-protected-2-aminophenols is reported. The utilization of the unique property and reactivity of the C=C triple bond in ynals leads to two consecutive conjugate additi

Full text of DOI:10.1021/ol400988e

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Synthesis of Benzoxazoles via an
Amine-Catalyzed [4 þ 1] Annulation
Aiguo Song,† Xiaobei Chen,† Xixi Song,† Xinshuai Zhang,† Shilei Zhang,† and
Wei Wang*,†,‡
Department of Chemistry and Chemical Biology, University of New Mexico,
Albuqueruqe, New Mexico 87131-0001, United States, and School of Pharmacy,
East China University of Science & Technology, Shanghai 200237, China
wwang@unm.edu
Received April 9, 2013
ABSTRACT
An unprecedented simple pyrrolidine catalyzed [4 þ 1] annulation reaction of ynals with N-protected-2-aminophenols is reported. The utilization of
the unique property and reactivity of the CtC triple bond in ynals leads to two consecutive conjugate addition reactions at the same β-position
with pyrrolidine via iminium activation. The powerful cascade process affords a new alternative approach to biologically and synthetically
important benzoxazoles in high yields (83ꢀ95%).
Organocatalysis has emerged as a powerful approach to
the construction of structurally diverse molecular archi-
tectures in the past decade.1 Aminocatalysis pioneered by
Barbas, List, and MacMillan has become the landmark of
the field.2,3 A number of unprecedented organic transfor-
mations havebeen realizedwiththestrategy. Furthermore,
capitalizing on reversible iminium-enamine catalysis,
many synthetically efficient catalytic cascade processes
have been developed for the facile construction of complex
molecular architectures.4 Notably, various cyclic ring
structures ranging from 3 to 7 membered sizes have been
constructed.5 Despite these impressive achievements, to
the best of our knowledge, there currently exists no
amine catalyzed [4 þ 1] annulation reaction to produce
five-membered rings.6ꢀ8 Thus, the identification of an
amine catalyzed [4 þ 1] annulation that is general and
operationally simple remains a prominent and challenging
goal. Toward this end, herein we wish to report a catalytic
platform for [4 þ 1] annulation. Notably, the process involv-
ing an unprecedented conjugate additionꢀprotonationꢀ
conjugate addition cascade sequence is catalyzed by simple
pyrrolidine using readily available N-tosyl-2-aminophenols
and ynals as reactants under mild reaction conditions to
† University of New Mexico.
‡ East China University of Science & Technology.
(1) (a) Berkessel, A.; Groeger, H. Asymmetric Organocatalysis: from
Biomimetic Concepts to Applications in Asymmetric Synthesis; Wiley-
VCH: 2005. (b) MacMillan, D. W. C. Nature 2008, 455, 304.
(2) (a) List, B.; Lerner, R. A.; Barbas, C. F., III. J. Am. Chem. Soc.
2000, 122, 2395. (b) Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C.
J. Am. Chem. Soc. 2000, 122, 4243.
(6) Kwon et al. developed elegant phosphine-catalyzed [4 þ 1]
annulations with allenoate esters: (a) Sriramurthy, V.; Barcan, G. A.;
Kwon, O. J. Am. Chem. Soc. 2007, 129, 12928. (b) Sriramurthy, V.;
Kwon, O. Org. Lett. 2010, 12, 1084. (c) Szeto, J.; Sriramurthy, V.; Kwon,
O. Org. Lett. 2011, 13, 5420.
(7) Xiao et al. reported powerful sulfur yilde involved [4 þ 1]
annulations and cascade processes: (a) Lu, L.-Q.; Chen, J.-R.; Xiao,
W.-J. Acc. Chem. Res. 2012, 45, 1278. (b) Lu, L.-Q.; Cao, Y.-J.; Liu,
X.-P.; An, J.; Yao, C.-J.; M., Z.-H.; Xiao, W.-J. J. Am. Chem. Soc. 2008,
130, 6946. (c) Lu, L.-Q.; Li, F.; An, J.; Zhang, J.-J.; An, X.-L.; Hua,
Q.-L.; Xiao, W.-J. Angew. Chem., Int. Ed. 2009, 48, 9542. (d) Lu, L.-Q.;
Li, F.; An, J.; Zhang, J.-J.; An, X.-L.; Hua, Q.-L.; Xiao, W.-J. Angew.
Chem., Int. Ed. 2009, 48, 9542. (e) Wang, X.-F.; Hua, Q.-L.; Cheng, Y.;
An, X.-L.; Yang, Q.-Q.; Chen, J.-R.; Xiao, W.-J. Angew. Chem., Int. Ed.
2010, 49, 8379. (f) An, J.; Lu, L.-Q.; Yang, Q.-Q.; Wang, T.; Xiao, W.-J.
Org. Lett. 2013, 15, 542.
(3) For recent reviews of aminocatalysis, see: (a) Lelais, G.; MacMillan,
D. W. C. Aldrichimica Acta 2006, 39, 79. (b) Mukherjee, S.; Yang, J. W.;
€
Hoffmann, S.; List, B. Chem. Rev. 2007, 107, 5471. (c) Erkkila, A.;
Majander, I.; Pihko, P. M. Chem. Rev. 2007, 107, 5416. (d) Bertelsen, S.;
Jørgensen, K. A. Chem. Soc. Rev. 2009, 38, 2178.
(4) For selected reviews of organocatalytic cascade reactions, see:
(a) Enders, D.; Grondal, C.; Huttl, M. R. M. Angew. Chem., Int. Ed.
2007, 46, 1570. (b) Yu, X.-H.; Wang, W. Org. Biomol. Chem. 2008, 6,
2036. (c) Ayaz, M.; van Berkel, S. S. Angew. Chem., Int. Ed. 2010, 49,
846. (d) Pellissier, H. Adv. Synth. Catal. 2012, 354, 237.
(5) For recent reviews on organocatalytic cyclization and cycloaddi-
tion, see: (a) Mayano, A.; Rios, R. Chem. Rev. 2011, 111, 4703. (b) Hong,
B.-C. In Enantioselective Organocatalyzed Reactions II; Mahrwald, R.,
Ed.; Springer: Dordrecht, 2011; Chapter 3, pp 187ꢀ244.
(8) Other examples of organocatalytic [4 þ 1] annulations: (a) Shi, Z.;
Tan, B.; Leong, W. W. Y.; Zeng, X.; Lu, M.; Zhong, G.-F. Org. Lett.
2010, 12, 5402. (b) Guo, Z.-W.; Xie, J.-W.; Chen, C.; Zhu, W.-D. Org.
Biomol. Chem. 2012, 10, 8471.
r
10.1021/ol400988e
XXXX American Chemical Society

give synthetically and biologically valuable benzoxazoles in
high yield.9
interest. However, recent studies reveal a number of inter-
esting chemistries beyond the original expectation.13,14 We
have developed unprecedented chiral allenamine cascade
reactions for the facile assembly of important molecular
architectures, which are difficulttoachieve withenal-based
reactions. In our continuing effort along this avenue, we
proposed a new amine catalyzed [4 þ 1] cyclization reac-
tion (Scheme 1). Given the importance of benzoxazoles in
synthesis and pharmaceuticals,9 we devised the binucleo-
philic N-tosyl-2-aminophenol substrates (2) for the pro-
posed [4 þ 1] annulation reaction with ynals 1. It is
hypothesized that activation of ynal 1 via iminium ion 4
renders the nucleophilic phenolꢀOH 2 conjugate to attack
the β-position. Protonation of the resulting allenamine 5
gives a new iminium ion 6. Then an intramolecular con-
jugate addition proceeds to form a benzoxazole ring 3.
Amine catalyzed 1,3-dipolar cycloaddition reactions for
the formation of five-membered rings have been subjected
to intensive studies.10 In these approaches, R,β-unsaturated
aldehydes are genreally used as essential substrates through
iminium activation with an amine promoter to react with
1,3-dipolar components such as nitrones11 and azomethine
ylides12 in a concerted or iminium-enamine stepwise
process. In contrast, the otherwise inaccessible modality,
[4 þ 1] annulation, offers an alternative versatile route to
five-membered scaffolds because of their readily availabil-
ity of starting materials. Nevertheless, a survey of literature
reveals that only a handful of organocatalyzed [4 þ 1]
annulation reactions are reported.6ꢀ8 Elegant examples
include Kwon’s phosphine promoted6 and Xiao’s sulfur
ylide7 [4 þ 1] annulations.
Although iminium catalysis with enals has enjoyed
great success,3 reactions with ynals have emerged slowly.
Limited examples of ynals in iminium catalysis have been
reported.13,14 This may be attributedtothe similar reaction
behaviors to enals, while a nonstereogenic center genera-
ted in conjugate addition adducts diminishes synthetic
Scheme 1. Proposed Amine Catalyzed [4 þ 1] Annulations
(9) Heterocyclic benzoxazoles are featured in numerous biologically
interesting molecules. A SicFinder substructure search with benzoxazole
results in more than 160 000 hits. Furthermore, bioactive indicators
reveal that they have broad and important biological properties
targeting the nervous system, as antitumor, -inflammatory, -infective,
-diabetic, and -obesity agents and cardiovascular, immune, and respira-
tory mediators.
(10) Recent reviews of [3 þ 2] cycloadditions: (a) Stanley, L. M.; Sibi,
M. P. Chem. Rev. 2008, 108, 2887. (b) Amblard, F.; Cho, J. H.; Schinazi,
R. F. Chem. Rev. 2009, 109, 4207. (c) Adrio, J.; Carretero, J. C. Chem.
Commun. 2011, 47, 6784.
(11) Nitrones: (a) Jen, W. S.; Wiener, J. J. M.; MacMillan, D. W. C.
J. Am. Chem. Soc. 2000, 122, 9874. (b) Karlsson, S.; Hoegberg, H.-E.
Eur. J. Org. Chem. 2003, 2782. (c) Gonzalez-Cruz, D.; Tejedor, D.; de
Armas, P.; Morales, E. Q.; Garcia-Tellado, F. Chem. Commun. 2006,
2798. (d) Du, W.; Liu, Y.-K.; Yue, L.; Chen, Y.-C. Synlett 2008, 2997.
(e) Weselinski, L.; Stepniak, P.; Jurczak, J. Synlett 2009, 2261. (f) Shen,
Z.-L.; Goh, K. K. K.; Wong, C. H. A.; Loo, W.-Y.; Yang, Y.-S.; Lu, J.;
Loh, T.-P. Chem. Commun. 2012, 48, 5856.
(12) Azomethine ylides: (a) Dambruoso, P.; Massi, A.; Dondoni, A.
Org. Lett. 2005, 7, 4657. (b) Chen, W.; Du, W.; Duan, Y.-Z.; Wu, Y.;
Yang, S.-Y.; Chen, Y.-C. Angew. Chem., Int. Ed. 2007, 46, 7667. (c)
Vicario, J. L.; Reboredo, S.; Bada, D.; Carrillo, L. Angew. Chem., Int.
Ed. 2007, 46, 5168. (d) Ibrahem, I.; Rios, R.; Vesely, J.; Cordova, A.
Tetrahedron Lett. 2007, 48, 6252. (e) Chen, X.-H.; Zhang, W.-Q.; Gong,
L.-Z. J. Am. Chem. Soc. 2008, 130, 5652. (f) Liu, Y.-K.; Liu, H.; Du, W.;
Yue, L.; Chen, Y.-C. Chem.;Eur. J. 2008, 14, 9873. (g) Chen, X.-H.;
Wei, Q.; Luo, S.-W.; Xiao, H.; Gong, L.-Z. J. Am. Chem. Soc. 2009, 131,
13819. (h) Suga, H.; Arikawa, T.; Itoh, K.; Okumura, Y.; Kakehi, A.;
Shiro, M. Heterocycles 2010, 81, 1669. (i) Shi, F.; Luo, S.-W.; Tao, Z.-L.;
He, L.; Yu, J.; Tu, S.-J.; Gong, L.-Z. Org. Lett. 2011, 13, 4680. (j) Sarotti,
A. M.; Spanevello, R. A.; Suarez, A. G.; Echeverria, G. A.; Piro, O. E.
Org. Lett. 2012, 14, 2556. (k) Shi, F.; Tao, Z.-L.; Luo, S.-W.; Tu, S.-J.;
Gong, L.-Z. Chem.;Eur. J. 2012, 18, 6885.
Although the proposed reaction appears simple, there
are significant barriers toovercome. Thefirst concernisthe
second conjugate reaction in the cascade. The significant
steric hindrance induced by β, β0-disubstituted enals ren-
ders the conjugate addition difficult. It is even more
difficult with a bulky protected “N” nucleophile. It should
be noted that the examples of β, β0-disubstituted enals in
aminocatalyzed conjugate additions are scarce.15 More-
over, the “O” added adduct 5 significantly reduces the
reactivity for the second conjugate addition reaction due
to the formation of a deactivated electron-rich enol ether.
Third, a condensation reaction between the highly active
aldehyde 1 and 2 could compete with the proposed [4 þ 1]
process.
(13) We have developed organocatalytic cascade reactions with
ynals: (a) Zhang, X.-S.; Zhang, S.-L.; Wang, W. Angew. Chem., Int.
Ed. 2010, 49, 1481. (b) Liu, C.; Zhang, X.-S.; Wang, R.; Wang, W. Org.
Lett. 2010, 12, 4948. (c) Zhang, X.-S.; Song, X-X.; Li, H.; Zhang, S.-L.;
Chen, X.-B.; Yu, X.-H.; Wang, W. Angew. Chem., Int. Ed. 2012, 51,
7282.
(14) Organocatalytic reactions with ynals from other research
groups: (a) Jones, S. B.; Simmons, B.; MacMillan, D. W. C. J. Am.
ꢀ
ꢀ~
Chem. Soc. 2009, 131, 13606. (b) Aleman, J.; Nunez, A.; Marzo, L.;
Marcos, V.; Alvarado, C.; Ruano, J. L. G. Chem.;Eur. J. 2010, 16,
9453. (c) Aleman, J.; Fraile, A.; Marzo, L.; Ruano, J. L. G.; Izquierdo,
C.; Diaz-Tendero, S. Adv. Synth. Catal. 2012, 354, 1665. (d) Cai, X.;
Wang, C.; Sun, J. Adv. Synth. Catal. 2012, 354, 359. (e) Dong, L.-J.; Fan,
T.-T.; Wang, C.; Sun, J. Org. Lett. 2013, 15, 204.
(15) To the best of our knowledge, amine catalyzed conjugate addi-
tions of β,β0-disubstituted enals are restricted to hydrogenations: (a)
Ouellet, S. G.; Tuttle, J. B.; MacMillan, D. W. C. J. Am. Chem. Soc.
2005, 127, 32. (b) Yang, J. W.; H. Fonseca, M. H.; Vignola, N.; List, B.
Angew. Chem., Int. Ed. 2005, 44, 108. (c) Tuttle, J. B.; Ouellet, S. G.;
MacMillan, D. W. C. J. Am. Chem. Soc. 2006, 128, 12662.
B
Org. Lett., Vol. XX, No. XX, XXXX

To test the validity of our proposed organocatalytic
[4 þ 1] annulation process, we probed a model reaction
of ynal 1a with N-tosyl-2-aminophenol (2a) in the presence
of simple pyrrolidine (20 mol %) as a promoter, which can
readily engage in iminium formation with aldehyde func-
tionality in ynal 1a (Table 1). To our delight, pyrrolidine
readily effects the [4 þ 1] annulation reaction. The reaction
proceeded smoothly to afford the desired benzoxazole 3a
in 5 min in good yield (75%, entry 1). Furthermore, under
the reaction conditions, we did not observe the con-
densation product between aldehyde 1a and N-tosyl-2-
aminophenol (2a). It is believed that under the mild non-
acidic conditions it is difficult to form the product, whose
formation requires an acid promoter. In addition, it appears
that the second conjugate addition reaction went smoothly.
This may be due to the intramolecular process. With
pyrrolidine as the catalyst, we examined the solvent effect
on the process (entries 2ꢀ5). Dichloroethane (DCE) was
identified as the optimal reaction medium for the reaction
(entry 5). In this instance, the reaction was accomplished in
5 min to produce product 3a in 84% yield. Furthermore,
notably, lowering the catalyst loading to 5 mol % gave an
even higher yield (93%) despite prolonging the reaction time
(15 h) (entry 6). The increase of the yield could be explained
by minimization of the undesired aldol reaction between
product 3a and reactant 1a, which was observed with a
20 mol % catalyst loading. Importantly, no product was
observed when a background reaction was carried out with-
out any catalyst (entry 7). Besides, TEA failed to promote the
reaction indicating that the [4 þ 1] annulation reaction did
not proceed via a base-catalyzed process (entry 8).
cases, uniformly high yields (85ꢀ93%) are achieved.
Furthermore, the pyrrolidine promoted process can be ex-
tended to aliphatic (entry 10) and heterocyclic (entry 11)
ynals with high efficiency. Structural variation of N-tosyl-2-
aminophenols is then probed (entries 12ꢀ18). The catalytic
system is generally applicable to a variety of N-tosyl-2-
aminophenols under the optimized conditions. Again, high
yields (83ꢀ92%) are achieved in these examples. However,
interestingly it appears that the substituents on the aro-
matic system have an impact on the reaction. The rate of
conversion with these substrates is noticeably slower than
without substituents regardless of the electron-donating
(entries 12ꢀ14 and 17) and -withdrawing groups that are
attached (entries 15ꢀ17 and 18). Therefore, the corre-
sponding reactions are carried out with 20 mol % catalyst
and at 40 °C for 24 h to facilitate these transformations.
Table 2. Scope of Pyrrolidine Catalyzed [4 þ 1] Annulation
Reactionsa
entry
R, X
3
% yieldb
1
Ph, H
3a
3b
3c
3d
3e
3f
93
88
95
92
89
85
93
86
91
88
91
91
89
83
87
84
92
90
2
4-FC6H4, H
4-ClC6H4, H
4-BrC6H4, H
4-NO2C6H4, H
4-CNC6H4, H
4-MeC6H4, H
4-MeOC6H4, H
3-MeC6H4, H
BnOCH2, H
2-thienyl, H
Ph, 4-Me
3
4
5
6
7
3g
3h
3i
8
9
Table 1. Optimization of Reaction Conditionsa
10
11
12c
13c
14c
15c
16c
17c
18c
3j
3k
3l
Ph, 5-Me
3m
3n
3o
3p
3q
3r
Ph, 4-t-Bu
Ph, 4-Cl
% yieldb
Ph, 4-NO2
entry
cat. (mol %)
solvent
t
4-ClC6H4, 4-Me
4-NO2C6H4, 4-Cl
1
2
3
4
5
6
7
8
pyrrolidine (20)
pyrrolidine (20)
pyrrolidine (20)
pyrrolidine (20)
pyrrolidine (20)
pyrrolidine (5)
none
CH2Cl2
5 min
5 min
5 min
5 min
5 min
15 h
75
73
69
61
84
93
0
CHCl3
a Reaction conditions: unless specified, see footnote a in Table 1.
b Isolated yields. c With pyrrolidine (0.020 mmol) at 40 °C for 24 h.
CH3CN
toluene
Cl(CH2)2Cl
Cl(CH2)2Cl
CH2Cl2
In addition, the pyrrolidine catalyzed [4 þ 1] annulation
reaction can be applied withBoc-protected 2-aminophenol
9 (Scheme 2, eq 1). Under similar reaction conditions
with 20 mol % catalyst, the process proceeded smoothly
to afford the desired product 10 in 91% yield. The [4 þ 1]
annulation product 10 can be deprotected to give 11 by
reduction with LiAlH4 in 82% yield (eq 2). Furthermore,
reduction of 10 to alcohol by NaBH4 followed by treat-
ment with TBAF afforded the cyclization product 12 in
79% yield in a two-step transformation (eq 3).
1 h
TEA
CH2Cl2
1 h
0
a Reactions were carried out with 1a (0.1 mmol) and 2a (0.11 mmol)
at rt in 0.2 mL of solvent. b Isolated yields.
The simple pyrrolidine catalyzed [4 þ 1] annulation
reaction serves as a general approach to structurally diverse
benzoxazoles under mild reaction conditions (Table 2). The
examination of the substrate scope of reactants ynals 1 has
revealed a significant tolerance (entries 1ꢀ16). In addition
to the unsubstituted ynal (entry 1), the aromatic ring
bearing electron-withdrawing (entries 2ꢀ6) and -donating
(entries 7ꢀ9) groups can be applied for the protocol. In all
Having demonstrated a simple pyrrolidine catalyzed
[4 þ 1] annulation reaction of ynals with N-tosyl/Boc-2-
aminophenols, we attempted to probe a catalytic enantio-
selective version with a chiral organocatalyst (Table S1 in SI).
Org. Lett., Vol. XX, No. XX, XXXX
C

Table 3. Addition Sequence Tests of [4 þ 1] Annulation Reactionsa
Scheme 2. Synthetic Elaboration of [4 þ 1] Annulation Products
entry
PhOH
PhNHTs
% yieldb
% yieldb
1
2
3
1.1 equiv
0.0 equiv
1.1 equiv
0.0 equiv
1.1 equiv
1.1 equiv
92
0
0
0
0
90
a Reaction condition: a mixture of PhOH (0.11 mmol) and/or
PhNHTs (0.11 mmol), 1a (0.1 mmol), and pyrrolidine (0.005 mmol) in
0.5 mL of DCE was stirred at rt for 15 h. b Isolated yields.
Although the addition sequence of “O” and “N” nucleo-
philes does not affect the structures of the reaction products,
the studies may help to understand their nucleophilic nature.
Furthermore, such insight may also assist in developing an
asymmetric version of the process. Under the same reaction
conditions we employed above (Table 3), we performed the
conjugate addition reactions of alkynal 1a with PhOH or
PhNHTs, respectively. Oxo-conjugate addition adduct 16
was formed in 92% yield (entry 1), while no detectable aza-
conjugate addition product 17 was observed (entry 2). The
competition reaction between PhOH and PhNHTs further-
more confirmed that the O nucleophile in 1 should be added
to alkynals first (entry 3). The “O” addition occurred first
which may be due to less hindrance. The results could help
us to develop an asymmetric synthesis of enantioenriched
benzoxazoles where the second conjugate addition is re-
sponsible for the formation of a stereogenic center.
Scheme 3. Rationalization of Low Enantioselectivity of Chiral
Amine Catalyzed [4 þ 1] Annulation
In conclusion, we have designed and implemented an
unprecedented amine-catalyzed [4 þ 1] annulation reac-
tion. The notable features of the process include a new
conjugate additionꢀprotonationꢀconjugate addition
cascade sequence by employing readily available ynals
and N-protected-2-aminophenols as reactants. Moreover,
an iminium-allenamine-iminium activation mode promoted
by simple pyrrolidine is reported for the first time. The mild
reaction protocol allows for a broad spectrum of ynals and
2-aminophenols to engage in the cascade sequence with high
efficiency. Furthermore, synthetically and biologically im-
portant benzoxazoles are created in a one-pot operation. The
development of enantioselective [4 þ 1] annulation reactions
for the formation of enantioenriched benzoxazoles and
expansion of the activation mode using underexplored ynals
in aminocatalysis are being pursued in our laboratory.
Disappointingly, very poor ee’s were observed in these
cases. The observed results could be rationalized in the
proposed model (Scheme 3). The “O”-centered nucleo-
philic species in 2 is involved in the first conjugate addition
(see below preliminary mechanistic study). The nucleophilic
addition could proceed in two possible ways, pathways a
and b, due to the linear geometry of the CtC triple bond
and lead to respective adducts 14 and 15. Compound 14 is
believed to be formed more favorably since the “O” attacks
the less steric side of a chiral amine derived iminium ion 13.
Furthermore, the bulky NHTs moiety in 14 and 15 is
oriented in position to minimize the interaction with the
big side chain of the catalyst. The new stereogenic center is
created in the second conjugate addition. However, the
chiral center of the catalyst (e.g., 14 and 15) is far away
from the conjugate addition reaction center in both cases.
Accordingly, it is expected that poor enantiocontrol
is observed in both chiral iminiums 14 and 15. This is
also evidenced in the chiral amine catalyzed nuelcophilic
conjugate addition of β,β0-disubstituted R,β-unsaturated
aldehydes. A very limited number of examples exhibiting
good enantioselectivity have been reported.15
Acknowledgment. Financial support from the NSF
(CHE-1057569) and East China University of Science
and Technology is gratefully acknowledged.
Supporting Information Available. Experimental pro-
cedures; 1H, 13C NMR and HRMS data for 2, 3, 10ꢀ12,
and 17. This material is available free of charge via the
Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX