Study on the reactions of acetylenic aldehydes with dimethyl phosphite in basic media: Phosphonate-phosphate rearrangement versus 5-exo-dig cyclization reactions

Article abstract of DOI:10.1002/adsc.201200276

Tandem reactions of various acetylenic aldehydes with dimethyl phosphite in basic media were investigated. It was shown that in the case of a non-activated triple bond of the starting materials, the well-known Pudovik reaction followed by a subsequent phosphonate-phosphate rearrangement took place. On the other hand when the triple bond of the starting materials is activated by electron-withdrawing heterocycles, a smooth and regioselective tandem 5-exo-dig cyclization reactions becomes possible.

Full text of DOI:10.1002/adsc.201200276

FULL PAPERS
DOI: 10.1002/adsc.201200276
Study on the Reactions of Acetylenic Aldehydes with
Dimethyl Phosphite in Basic Media: Phosphonate-Phosphate
Rearrangement versus 5-exo-dig Cyclization Reactions
Inga Cikotienea,* and Rita Buksnaitienea
a
Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, LT-03225 Vilnius, Lithuania
Fax : (+370)-5-233-0987; phone: (+370)-5-219-3195 or (+370)-5-219-3187; e-mail: inga.cikotiene@chf.vu.lt
Received: April 3, 2012; Revised: June 25, 2012; Published online: September 28, 2012
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200276.
Abstract: Tandem reactions of various acetylenic al- starting materials is activated by electron-withdraw-
dehydes with dimethyl phosphite in basic media ing heterocycles, a smooth and regioselective tandem
were investigated. It was shown that in the case of 5-exo-dig cyclization reactions becomes possible.
a non-activated triple bond of the starting materials,
the well-known Pudovik reaction followed by a sub- Keywords: acetylenic aldehydes; phosphonate-phos-
sequent phosphonate-phosphate rearrangement took phate rearrangement; regioselective 5-exo-dig cycli-
place. On the other hand when the triple bond of the zation; tandem nucleophilic addition
Introduction
matic compounds (anilines, phenols, thiophenes and
pyrroles).
Over the past few years, a huge variety of intramolec-
In the 2008 a paper entitled “Efficient Syntheses of
ular cyclizations of acetylenic aldehydes with nucleo- (Thio)phosphonylated Isobenzofurans by Tandem Nu-
philic components has been studied. These reactions cleophilic Addition and Regioselective 5-exo-dig Ad-
are a powerful and atom-economic strategy for the dition to Carbon-Carbon Triple Bond: Cooperative
construction of dihydrofuran and dihydropyran deriv- Effect to 1,8-DiazabicycloACTHNUTRGNEU[GN 5.4.0]undec-7-ene (DBU)”
atives via 5-exo-dig or 6-endo-dig cyclization modes by Z. Miao, R. Chen and co-workers was published.[4]
(Scheme 1). During these transformations transition According to the procedure in this paper, various iso-
metal catalysts,[1] electrophiles[2] and bases[3] can be benzofuran (thio)phosphonate derivatives (3) or (3’)
employed as activating agents; and the choice of acti- were prepared by means of via cooperative DBU in-
vation has a crucial influence on the regioselectivity tramolecular cyclization of o-alkynylbenzaldehydes or
of the reactions. The roles of nucleophiles are usually o-alkynylacetophenones (2) and dialkyl phosphite or
played by various alcohols, amides and activated aro- dialkyl phosphonothioate (1) (Scheme 2).
During the continuation of our ongoing program
aimed at alkynyl-substituted heterocycles[5] in the syn-
thesis of various condensed compounds, we became
particularly interested in the results of Miao and
Chen, especially in the phenomenon of 1,5-sigmatrop-
ic hydrogen or methyl shifts[4] and in the novel use of
phosphorus nucleophiles for tandem intramolecular
cyclizations of acetylenic aldehydes. Having in mind
the fact that carbocyclic and heterocyclic substrates
can react by different pathways, we decided to study
the reactions of various starting alkynylaldehydes
containing quinoline and pyrimidine rings with di-
methyl phosphite in basic media. However, to our sur-
prise, our obtained results were not consistent with
the previously published results of Miao and Chen.
Scheme 1. Literature results.
Moreover, we noted interesting evidence that the re-
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Scheme 2. Results published by Miao, Chen and co-workers.[4]
action outcome mainly depends on the electron densi- of isolated products 6a–d there were doublets for
ꢀ
ty on the C C triple bond. In order to shed some equivalent methoxy groups at 3.75–3.79 ppm and dou-
light on the reactions of acetylenic aldehydes with di- blets of doublets for methylene groups at 5.32–
alkyl phosphites in basic media herein we present the 5.48 ppm with the coupling constants of 7.2–7.8 Hz
results of our investigations.
and 0.9 Hz, respectively. The smaller couplings were
due to splitting of methylene groups to the proton at
the quinoline ring position 4, what was well-seen from
À
Results and Discussion
the H,H-correlation spectra and multiplicity of C-4 H
(d, J=0.9 Hz). In the 13C NMR spectra of 6a–d there
First of all we prepared the corresponding 2-alkynyl- were two signals at 73.1–86.0 and 94.9–104.9 ppm re-
ꢀ
quinoline-3-carbaldehydes 4a–e and 6-alkynylpyrimi- gions, peculiar to the carbons of C C bonds. And fi-
dine-5-carbaldehydes 5a–k (Figure 1). For the prepa- nally, the presence of an alkynyl moiety in the prod-
ration of the starting materials we utilized the classi- ucts was proved by IR spectra, where we found the
cal Sonogashira coupling[6] between commercially sharp absorption peaks at 2212–2233 cmÀ1. The inter-
available 2-chloroquinoline-3-carbaldehyde or 4- mediates 7a, b were isolated and fully characterized
chloro
lenes.
ACHTUNGTRENNUNG
Then we tried to apply Miao, Chen and co-workers tandem 5-exo-dig reactions of 2-alkynylquinoline-3-
procedure for the synthesis of dimethyl furo[3,4- carbaldehydes (4) with phosphorus nucleophiles are
b]quinolin-1-ylphosphonates or dimethyl 1,3- impossible, because of more favourable phosphonate-
dihydrofuro[3,4-b]quinolin-1-ylphosphonates. When phosphate rearrangement process of the products of
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
the mixtures of compounds 4a–d, dimethyl phosphite the Pudovik reaction. However, to our pleasant sur-
and DBU were stirred at 508C temperature, we ob- prise, when 2-(2-pyridinylethynyl)quinoline-3-carbal-
served the quick and selective conversions of the dehyde 4e was treated with dimethyl phosphite in the
starting materials by TLC. The same outcome of the presence of potassium tert-butoxide in dichloroethane
reactions was observed when we change DBU to po- at room temperature the formation of cyclized prod-
tassium tert-butoxide in dichloroethane. The spectral uct 8 took place (Scheme 3).
1
elucidation of purified products 6a–d led us to con-
In the H NMR spectrum of 8 there were two dou-
clude that under the reaction conditions the Pudovik blets for diastereotopic methoxy groups at 3.65 and
reaction[7] and phosphonate-phosphate rearrange- 3.93 ppm, respectively. The signal of proton at C-1 of
1
ment[8] sequences took place. In the H NMR spectra the dihydrofuran ring appeared as doublet at
6.13 ppm with a coupling constant 8.4 Hz. The proton
of ethene moiety appeared as a singlet at 7.03 ppm.
Neither 13C NMR, nor IR spectra showed the pres-
ꢀ
ence of a C C bond. These data together with
HSQC, HMBC, TOCSY spectra and molecular for-
mula obtained by HR-MS confirmed the structure of
8.
Therefore, we assumed that activation of the triple
bond by electron-withdrawing quinoline and pyridine
Figure 1. Starting materials. [4: R=Ph (a); c-Pr (b); t-Bu (c);
n-Bu (d); 2-pyridyl (e). 5: R=H; R’=N
R=H; R’=N(CH2)4O; R’’=Ph (b); R=SCH3; R’=
(C2H5)2; R’’=Ph (c); R=SCH3; R’=N(C2H5)2; R’’=4-
CH3C6H4 (d); R=SCH3; R’=N(C2H5)2; R’’=4-C2H5C6H4
(e); R=SCH3; R’=N(CH2)4O; R’’=Ph (f); R=SCH3; R’=
NHPh; R’’=Ph (g); R=SCH3; R’=NHC2H5; R’’=Ph (h);
R=SCH3; R’=N(CH2)4O; R’’=Bu (k)].
ACHTUGNTRENN(UNG CH2)4; R’’=Ph (a);
moieties in the starting compound 4e is sufficient for
enabling a tandem cyclization reaction. The formation
of rearrangement products 6 and cyclization product
8 takes place via the same intermediates 7. The latter
compounds can undergo phosphonate-phosphate rear-
rangement via a three-membered transition state
ACHTUNGTRENNUNG
N
N
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
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Study on the Reactions of Acetylenic Aldehydes with Dimethyl Phosphite in Basic Media
Scheme 3. Reagents and conditions: i) dimethyl phosphite (2 equiv.), DBU (2 equiv.), THF, 508C, 2–3 h. or dimethyl phos-
phite (2 equiv), KO-t-Bu (2 equiv.), DCE, 508C, 2 h.
(Scheme 3, pathway a). On the other hand, when the doublets with small coupling constants at 6.51–
1
ꢀ
C C bond is activated by electron-withdrawing moi- 6.62 ppm in the H NMR spectra and signals in the
eties, the tandem 5-exo-dig cyclization reaction takes 13C NMR spectra at 100.86–103.52 ppm. Neither
place (Scheme 3, pathway b).
13C NMR nor IR spectra indicated the presence of
ꢀ
It is obvious, that the triple bond of the starting C C bonds. The molecular formulae obtained from
pyrimidine substrates 5 is more activated due to the HR-mass spectra corresponded to the composition of
electron-deficient pyrimidine moiety and its formyl 9a–f.
group, so we envisioned that the pyrimidines 5 could
be able to undergo the smooth tandem cyclization by X-ray crystallographic analysis (Figure 2).[9]
process with dimethyl phosphite in basic media. It is noteworthy, that compounds 5g and 5h bearing
Moreover the structure of 9d was firmly confirmed
Indeed, after the treatment of starting compounds 5a– a secondary ethylamino or anilino group in position 4
f with dimethyl phosphite and potassium tert-butoxide
in dichloroethane at room temperature, the smooth
and regioselective reactions were observed by TLC
(Scheme 4). Transformations of the starting com-
pounds were completed in 30 min. when 1 equivalent
of base was used. Potassium tert-butoxide gave the
best results in terms of yields and duration. While po-
tassium carbonate and DBU provided a slightly lower
yield of the cyclized products than tert-butoxide, Et3N
proved to be far less effective. Moreover, we did not
succeed to isolate the Pudovik addition intermediates
from the reaction mixtures. This fact indicated that
during the treatment of 6-alkynylpyrimidine-5-carbal-
dehydes 5 with dimethyl phosphite in basic media, the
tandem nucleophilic addition–cyclization reactions
took place (Scheme 4).
1
In the H NMR spectra of compounds 9a–f besides
of other signals there were two doublets of diastereo-
Scheme 4. Reagents and conditions: i) Dimethyl phosphite
topic methoxy groups at 3.53–3.60 ppm and 3.81–
(1.2 equiv), KO-t-Bu (1 equiv.), DCE, room temperature,
3.89 ppm, respectively. In the 13C NMR spectra of 9a–
30 min. Compounds 9: R=H; R’=NACTHNUTRGNEUNG(CH2)4; R’’=Ph (a);
f doublets at 80.13–80.88 ppm with the coupling con-
stants of 163–166 Hz due to resonances of O C-5 P
of dihydrofuran rings were observed. The presence of
R=H; R’=N
(C2H5)2; R’’=Ph (c); R=SCH3; R’=N
CH3C6H4 (d); R=SCH3; R’=N(C2H5)2; R’’=4-C2H5C6H4
(CH2)4O; R’’=Ph (f).
ACHTUNGTRENNUNG
À
À
N
N
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
an ethene moiety was proved by the broad singlets or (e); R=SCH3; R’=NACHTNUGTRENNUNG
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So, it could be concluded that the tandem nucleo-
philic addition–cyclization reactions of acetylenic al-
dehydes with dialkyl phosphites are possible only in
ꢀ
the case of electron-poor C C bonds, activated by
electron-withdrawing pyridine and pyrimidine rings.
When the activation of an alkyne moiety is unsuffi-
cient, the classical Pudovik reaction followed by
a phosphonate–phosphate rearrangement takes place.
In the light of these facts we turned our attention
to the contrary results published earlier.[4] The triple
bonds of o-alkynylbenzaldehydes and o-alkynylaceto-
phenones are electron-rich, so the fact that these ma-
terials undergo smooth tandem 5-exo-dig cyclization
reaction with dialkyl phosphites in basic media dis-
AHCTUNGTRENNUNG
Figure 2. ORTEP view of compound 9d.
of the pyrimidine ring did not undergo cyclization re- the optimized reaction of the substrates with dimethyl
actions with dimethyl phosphite. In both these cases phosphite (Scheme 5). After quick and selective con-
the starting materials were recovered after the work- versions of the starting materials and purification of
up of reaction mixtures. We suppose, that compounds products 3a, 3’a and 3’e, we performed careful struc-
5g and 5h exist in the unfavourable conformation ture elucidations and moreover, we turned our atten-
where carbonyl group is turned towards the NHR tion to the spectral data of isobenzofuran-1-ylphos-
moiety to form an intramolecular hydrogen bond and
directed away from the C C bond, therefore tandem
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ꢀ
reactions become impossible. The same consistent should be noted that, besides minor discrepancies be-
pattern was observed during investigation of tandem tween chemical shifts, we obtained the same NMR
reactions of 4-alkynylpyrimidine-5-carbaldehydes with spectra as Miao et al.[4]
alcohols in basic media.[5i] Moreover, the reaction of
In the H NMR spectra of 3a, 3’a and 3’e, there
1
the starting material 5k, bearing an alkyl moiety on were doublets for methylene groups at 5.20–5.32 ppm.
the alkynyl substituent, with dimethyl phosphite in The coupling constants of 7.1–7.5 Hz pointed to vici-
basic media was complicated, leading to the mixture nal coupling to neighbouring phosphorus nuclei
of various products (observed by TLC).
(Scheme 5). In the 13C NMR spectra of 3a, 3’a and 3’e
Scheme 5. Reaction between 2-alkynylbenzaldehydes (2) and dimethyl phosphite (1) in basic media. Reagents and condi-
tions: i) dimethyl phosphite (2 equiv.), DBU (2 equiv.), THF, 508C, 2–10 h.
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Study on the Reactions of Acetylenic Aldehydes with Dimethyl Phosphite in Basic Media
Figure 3. The HSQC spectrum of 3’a.
besides, other signals, there were doublets at 66.92– 3’a), and at 5.19 and 5.21 ppm (for compound 3’e) are
67.43 with coupling constants of 5.03–5.1 Hz indicat- doublets due to phosphorus coupling, but not chemi-
ing the presence of CH2OP moieties. Moreover, there cally shifted singlets. The same evidence was seen
1
were pairs of triple bond carbon signals at 86.08 and when the H NMR spectra of 3’a and 3’e were run at
94.42, at 77.17 and 95.78, and at 80.12 and 82.46 ppm a different fields (300 and 400 MHz operating fre-
respectively. And finally, in the IR spectra of 3a, 3’a quency).
and 3’e, there were weak absorption bands at 2102–
ATP (attached proton test) and DEPT (distortion-
2226 cmÀ1 indicating the presence of C C bonds. All less enhancement by polarization transfer) spectra
these data led us to conclusion that under the reaction showed that the 13C signals at 66.92–67.43 ppm are of
conditions the classical Pudovik reaction[7] followed CH2 groups, and the signals at 86.08 and 94.42 ppm
by phosphonate–phosphate rearrangement[8] had (for compound 3a), at 77.17 and 95.78 ppm (for com-
taken place. During these transformations the triple pound 3’a), and at 80.12 ppm (for compound 3’e) are
bonds of the starting materials remained unchanged. unprotonated carbons. The cross-peak in the HetCor
Therefore, the structures of 3a, 3’a and 3’e could be and HSQC spectra of 3’a between two protons signals
ꢀ
the corresponding dimethyl (2-alkynylphenyl)methyl- at 5.23 ppm and 13C signal at 67.28 ppm indicated that
phosphates (Scheme 5).[10]
signal at 5.23 ppm in the H NMR spectrum belongs
1
However, in the original publication the NMR to the methylene group (Figure 3). The analogous cor-
spectra of 3a, 3’a and 3’e were differently interpreted relation was seen from the HSQC spectra of com-
and other structures for final compounds were pro- pound 3’e (see the Supporting Information).
posed (see ref.[4] and the Supporting Information).
The cross-peak in the HetCor and HSQC spectra
In order to definitely confirm the structures of com- of 3’e between the proton signal at 3.35 ppm and the
pounds 3a, 3’a and 3’e several additional NMR ex- carbon signal at 82.97 ppm showed the presence of
periments were run. First of all, the phosphorus-de- a terminal alkyne moiety. Moreover, HMBC spectra
1
coupled H NMR spectra of 3’a and 3’e showed that of all three compounds 3a, 3’a and 3’e showed correla-
pairs of peaks at 5.26 and 5.28 ppm. (for compound tions between two ethynyl carbons and protons of the
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FULL PAPERS
Figure 4. The HMBC spectrum of 3’a.
attached groups and characteristic three cross-peaks between CH3 and CH groups in the COSY spectrum
between protons of CH2 groups and three aromatic of 3’c confirmed this coupling. 13C NMR and IR spec-
ꢀ
carbons. The HMBC spectrum of compound 3’a is tra showed the presence of the C C bond, the multi-
presented in Figure 4.
plicities of all carbons were verified by ATP experi-
Following one reviewerꢁs useful comment, we pre- ments. All these results showed that the report about
pared 1-[2-(1-hexynyl)phenyl]ethanone 2d, which was tandem nucleophilic addition–cyclization reaction of
also be used in original publication and performed its o-alkynylbenzaldehydes or o-alkynylacetophenones
reaction with dimethyl phosphite in the presence of with dialkyl phosphites or dialkyl phosphonothioates
DBU. After the isolation and spectral analysis of in the presence of 1,8-diazabicyclo
compound 3’c we were thoroughly persuaded that an ene[4] was erroneous.
analogous phosphonate–phosphate rearrangement
ACHTUNGTREN[NGNU 5.4.0]undec-7-
had taken place (Scheme 6). In the 1H NMR spectrum
of 3’c there was a characteristic doublet for the Conclusions
methyl group at 1.64 ppm with coupling to the neigh-
bouring CH proton (J=6.3 Hz). The correlation peak It was found that various acetylenic aldehydes under-
go smooth reactions with dimethyl phosphite in basic
media. The outcome of the reactions is dictated by
the electron density on the alkyne moiety. Electron-
rich substrates undergo the classic Pudovik reaction
followed by phoshonate–phosphate rearrangement.
On the other hand, when the triple bond of the start-
ing materials is activated by electron-withdrawing het-
erocycles, the novel tandem 5-exo-dig cyclization re-
actions take place. Our observed results disagree with
those previously published in Miao and co-workers
Scheme 6. Reagents and conditions: i) dimethyl phosphite
(2 equiv.), DBU (2 equiv.), THF, 508C, 24 h.
work[4] and moreover, bring some novelty to the un-
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Study on the Reactions of Acetylenic Aldehydes with Dimethyl Phosphite in Basic Media
running of HSQC, HMBC and TOCSY spectra of compound
8.
derstanding of cyclizations of functionally substituted
alkynes.
Experimental Section
References
The spectroscopic data of all synthesized compounds are
given in the Supporting Information.
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General Procedure for the Synthesis of Dimethyl (2-
Alkynylphenyl)methylphosphates (3a,3’a,3’e), Di-
methyl 1-[2-(1-Hexynyl)phenyl]ethylphosphate (3’c),
Dimethyl (2-Alkynyl-3-quinolinyl)methylphos-
phates (6a–d) and Dimethyl [(3Z)-1,3-Dihydro-3-(2-
pyridinylmethylene)furo
yl]phosphate (8)
ACHTUNGTREN[NUNG 3,4-b]quinolin-1-
o-Alkynylbenzaldehyde (2a, c f), o-alkynylacetophenone
(2d) or 2-alkynylquinoline-3-carbaldehyde (4) (0.5 mmol) in
THF (4 mL) was added dropwise to a stirred mixture of di-
methyl phosphite (0.11 g, 1.0 mmol) and DBU (0.153 g,
1.0 mmol) in THF (4 mL) at room temperature with TLC
(silica gel) monitoring. After 2–24 h stirring at 508C, the
mixture was cooled to room temperature and worked-up
with water (5 mL). The resulting mixture was then extracted
by AcOEt and dried with anhydrous sodium sulfate. After
concentration, the residue was purified by gradient column
chromatography (silica gel, AcOEt/hexane) to afford the
products 3, 6 and 8. The same results can be reached by
using potassium tert-butoxide (1 mmol) in dichloroethane
(5 mL).
Procedure for the Synthesis of Dimethyl [(7Z)-5,7-
Dihydro-2,4-disubstituted-7-(arylmethylene)furoACHTUNTRGNEUNG[3,4-
d]pyrimidin-5-yl]phosphates (9a–f)
2,4-Disubstituted-6-arylalkynylpyrimidine-5-carbaldehyde
(5a–f) (0.5 mmol) in DCE (5 mL) was added dropwise to
a stirred mixture of dimethyl phosphite (0.11 g, 1.0 mmol)
and potassium tert-butoxide (0.056 g, 0.5 mmol) in DCE
(4 mL) at room temperature with TLC (silica gel) monitor-
ing. After 30 min stirring at room temperature, the mixture
was washed with water (2ꢂ15 mL). The organic layer was
dried with anhydrous sodium sulfate. After concentration,
the residue was purified by gradient column chromatogra-
phy (silica gel, AcOEt/hexane) to afford the products 9a–f.
Acknowledgements
The research was funded by the European Social Fund under
ˇ
the Global Grant measure (Grant No. VP1-3.1-SMM-07K-
01–002). The authors thank Dr. Martin Murray (Bristol Uni-
versity, U.K.) for the expertise on NMR data and for the sug-
gestion of some NMR experiments. Mrs. Maryte Kreneviciene
(Vilnius University) is thanked for the recording of all regular
NMR spectra and for helpful discussions. Mr. Marius Morku-
nas (Tuebingen University) is kindly acknowledged for the
recording of 1H-{31P} NMR, DEPT, HSQC and HMBC spec-
tra of compounds 3a, 3a and 3e. Dr. Tadeusz Bieg (Silesian
University of Technology) is kindly acknowledged for the
[6] K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron
Lett. 1975, 16, 4467.
[7] a) A. N. Pudovik, M. A. Pudovik, J. Gen. Chem. USSR
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Adv. Synth. Catal. 2012, 354, 2719 – 2726
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2725

Inga Cikotiene and Rita Buksnaitiene
FULL PAPERS
[9] CCDC 874365 (9d) contains the supplementary crystal-
lographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_re-
quest/cif or on request to Cambridge Crystallographic
Data Center, 12 Union Road, Cambridge CB2 1EZ,
U.K. Crystal structure analysis for 9d: C21H28N3O4PS,
Mr =449.510 gmolÀ1, monoclinic, space group P 21/c,
a=10.5209(2), b=19.0797(4), c=12.1081(3) ꢇ, a=g=
90.00, b=113.7875(10), V=2224.05(8) ꢇ3, 1=
1.342 gcmÀ3, F
ACTHUNRTGNE(GNU 000)=952.
[10] The splitting patterns of 3a, 3’a and 3’e in their NMR
spectra are similar to the splitting in NMR spectra of
the known compound dimethyl benzylphosphate: C.
Lherbet, R. Castonguay, J. W. Keillor, Tetrahedron Lett.
2005, 46, 3565.
2726
asc.wiley-vch.de
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 2719 – 2726