Tandem reactions initiated by the oxidative decarboxylation of 1-benzoyl-2(S)-tert-butyl-6(S)-carboxyperhydropyrimidin-4-one

Article abstract of DOI:10.1016/S0040-4039(02)01066-3

Treatment of the title perhydropyrimidinone with diacetoxyiodobenzene and iodine followed by addition of allyltrimethylsilane and boron trifluoride etherate afforded 1-benzoyl-2(S)-tert-butyl-2,3-dihydro-4(H)-pyrimidin-4-one in 65-71% yield, via an efficient three-step radical decarboxylation-oxidation-β-elimination tandem reaction. In contrast, when addition of allyltrimethylsilane/BF₃·OEt₂ was suppressed, a remarkable five-step tandem process led to the formation of vinylic iodide, 1-benzoyl-2(S)-tert-butyl-5-iodo-2,3-dihydro-4(H)-pyrimidin-4-one as the main product.

Full text of DOI:10.1016/S0040-4039(02)01066-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5297–5300
Tandem reactions initiated by the oxidative decarboxylation of
1-benzoyl-2(S)-tert-butyl-6(S)-carboxyperhydropyrimidin-4-one
Mart´ın A. Iglesias-Arteaga, C. Gabriela Avila-Ortiz and Eusebio Juaristi*
Departamento de Qu´ımica, Centro de Investigacio´n y de Estudios Avanzados del Instituto Polite´cnico Nacional,
Apartado Postal 14-740, 07000 Me´xico, D.F. Mexico
Received 20 May 2002; accepted 30 May 2002
Abstract—Treatment of the title perhydropyrimidinone with diacetoxyiodobenzene and iodine followed by addition of allyltrimethyl-
silane and boron trifluoride etherate afforded 1-benzoyl-2(S)-tert-butyl-2,3-dihydro-4(H)-pyrimidin-4-one in 65–71% yield, via an
efficient three-step radical decarboxylation-oxidation-b-elimination tandem reaction. In contrast, when addition of allyltrimethyl-
silane/BF3·OEt2 was suppressed, a remarkable five-step tandem process led to the formation of vinylic iodide, 1-benzoyl-2(S)-tert-
butyl-5-iodo-2,3-dihydro-4(H)-pyrimidin-4-one as the main product. © 2002 Elsevier Science Ltd. All rights reserved.
Synthetic applications of diacetoxyiodobenzene have
received considerable attention.1 In a series of relevant
papers, Sua´rez and co-workers2 have presented diace-
toxyiodobenzene/iodine (DIB/I2) as an effective mixture
of reagents for the oxidative decarboxylation of car-
boxylic acids (Eq. (1)).
6(S)-carboxy-2,3-dihydro-4(H)-pyrimidin-4-one, 1, a
useful intermediate for the enantioselective synthesis of
a-substituted b-amino acids,4,5 was treated with the
DIB/I2/allyltrimethylsilane/BF3·OEt2 reagent mixture
(Eq. (3)). Although the anticipated allylated derivative
2 was not observed, interesting three- and five-step
tandem processes led to the formation of other valuable
decarboxylated products.
DIB/I
-CO
2
2
RꢀCO2HꢀꢀꢀꢀꢀꢁRꢀCO2IꢀꢀꢀꢀꢁRI
(1)
We were particularly interested by a recent application
of the Sua´rez oxidation, where the radical decarboxyla-
tion–oxidation of a-amino acids is followed by nucle-
ophilic trapping of the generated iminium ion (Eq.
(2)).3
With the aim to achieve overall substitution of the
carboxylic group in pyrimidinone 1 by an allyl moiety
(cf. Eq. (3)), the former substrate was treated with DIB
(2 equiv.) and iodine (1 equiv.) in CH2Cl2, followed by
allyltrimethylsilane (allylTMS, 5 equiv.) and BF3·OEt2
(1 equiv.), under the same conditions employed by
Sua´rez et al.3 in the corresponding transformation of
In this report, we describe the contrasting reaction
course encountered when 1-benzoyl-2(S)-tert-butyl-
(2)
(3)
Keywords: pyrimidinones; decarboxylation; elimination reactions; radicals and radical reactions; allenes.
* Corresponding author. E-mail: juaristi@relaq.mx
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01066-3

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Scheme 1.
pyroglutamic acid (Eq. (2)). Unexpectedly, the previ-
ously reported4b,i heterocyclic enone 3 was formed in
good yield (Eq. (3)).
Based on reasonable mechanistic considerations,2,3 the
formation of enone 3 can be accounted for in terms of
a three-step radical decarboxylation–oxidation–b-elimi-
nation tandem reaction as outlined in Scheme 1. It is
evident that b-elimination of an acidic proton in
iminium ion 5 to give enone 3 is faster than nucle-
ophilic addition to afford allylated product 2 (Eq. (3)
and Scheme 1).
Nevertheless, when the allylTMS/BF3·OEt2 reagent
mixture was suppressed from the reaction protocol, the
main product turned out to be vinylic iodide 4,6 accom-
panied by varying amounts of the enone 3 (Eq. (4)).
It is likely that the iodoenone 4 forms from enone 3 via
b-iodination;7 therefore, the former iodinated enone is
apparently generated from a remarkable five-step
tandem reaction: (1) radical decarboxylation of pyrim-
idinone 1, (2) oxidation to an iminium ion intermediate,
(3) b-elimination of a proton to give the enone 3, (4)
b-iodination, and (5) b-elimination of a second proton
at C(5) to produce iodoenone 48 (Scheme 1).
Figure 1. ORTEP drawing of iodoenone 7, with thermal
ellipsoids drawn at 30% probability level.10
Repeated attempts to obtain suitable crystals of
iodoenone 4 for crystallographic studies were unsuc-
cessful. Nevertheless satisfactory crystals of 1-benzoyl-
2(S)-isopropyl-5-iodo-2,3-dihydro-4(H)-pyrimidin-4-
one, 7,9 could be obtained. Fig. 1 shows the crystal
structure of iodoenone 7, an isopropyl analog of 4.
(4)

M. A. Iglesias-Arteaga et al. / Tetrahedron Letters 43 (2002) 5297–5300
5299
(c) Francisco, C. G.; Gonza´lez, C. C.; Sua´rez, E. Tetra-
hedron Lett. 1997, 38, 4141–4144; (d) Boto, A.; Herna´n-
dez, R.; Sua´rez, E. Tetrahedron Lett. 1999, 40,
5945–5948. For recent applications of the Sua´rez
iodine(III) oxidation, see: (e) Lee, S.; Fuchs, P. L. Org.
Lett. 2002, 4, 317–318; (f) Boto, A.; Herna´ndez, R.;
Sua´rez, E. Tetrahedron Lett. 2002, 43, 1821–1824.
3. Boto, A.; Herna´ndez, R.; Sua´rez, E. J. Org. Chem. 2000,
65, 4930–4937.
4. (a) Chu, K. S.; Negrete, G. R.; Konopelski, J. P. J. Org.
Chem. 1991, 56, 5196–5202; (b) Juaristi, E.; Quintana, D.
Tetrahedron: Asymmetry 1992, 3, 723–726; (c) Lakner, F.
J.; Chu, K. S.; Negrete, G. R.; Konopelski, J. P. Org.
Synth. 1995, 73, 201–214; (d) Juaristi, E.; Quintana, D.;
Balderas, M.; Garc´ıa-Pe´rez, E. Tetrahedron: Asymmetry
1996, 7, 2233–2246; (e) Juaristi, E.; Lo´pez-Ruiz, H.;
Madrigal, D.; Ram´ırez-Quiro´s, Y.; Escalante, J. J. Org.
Chem. 1998, 63, 4706–4710; (f) Juaristi, E.; Balderas, M.;
Ram´ırez-Quiro´s, Y. Tetrahedron: Asymmetry 1998, 9,
3881–3888; (g) Juaristi, E.; Balderas, M.; Lo´pez-Ruiz, H.;
Jime´nez-Pe´rez, V. M.; Kaiser-Carril, M. L.; Ram´ırez-
Quiro´s, Y. Tetrahedron: Asymmetry 1999, 10, 3493–3505;
(h) Seebach, D.; Boog, A.; Schweizer, W. B. Eur. J. Org.
Chem. 1999, 335–360; (i) Juaristi, E. In 1-Benzoyl-2(S)-
tert-butyl-3-methylperhydropyrimidin-4-one; Paquette, L.
A.; Rigby, J. H.; Roush, W. R.; Wipf, P., Eds. e-EROS;
http://www3.interscience.wiley.com/reference.html, July,
2002.
5. For general reviews on the enantioselective synthesis of
b-amino acids, see: (a) Juaristi, E.; Quintana, D.;
Escalante, J. Aldrichimica Acta 1994, 27, 3–11; (b) Cole,
D. C. Tetrahedron 1994, 50, 9517–9582; (c) Cardillo, G.
Tomasini, C. Chem. Soc. Rev. 1996, 25, 117–128; (d)
Enantioselective Synthesis of i-Amino Acids; Juaristi, E.,
Ed.; Wiley-VCH: New York, 1997; (e) Juaristi, E.;
Lo´pez-Ru´ız, H. Curr. Med. Chem. 1999, 6, 983–1004.
6. Synthetic procedure and spectroscopic data: A mixture of
the pyrimidinone 1 (304 mg, 1 mmol), DIB (644 mg, 2
mmol) and iodine (253 mg, 1 mmol) was stirred in
CH2Cl2 (20 ml) until TLC showed disappearance of the
starting material (3–4 h). After addition of CH2Cl2 (20
ml), the reaction mixture was washed with 5% aqueous
Na2S2O3 (4×10 ml), 3% aqueous NaHCO3 (2×10 ml), and
brine (1×10 ml), dried (Na2SO4) and evaporated to a pale
yellow syrup which solidifies on standing and was
crushed and washed with hexane to afford 219 mg of a
1/1.6 mixture of the enone 3 and the iodoenone 4 (deter-
mined by NMR). Repeated crystallization from EtOAc/
hexane and CH2Cl2/hexane afforded 138 mg (36%) of the
pure iodoenone 4. Mp 258–260°C (descomp.). [h]2D5=
428.4 (c=1.0, CHCl3). 1H NMR (400 MHz, DMSO-d6,
120°C) l (ppm) 0.94 (s, 9H); 5.62 (d, J=3.3 Hz, 1H);
7.56–7.52 (m, 6H); 8.25 (broad, 1H). 13C NMR (100
MHz, DMSO-d6, 120°C) l (ppm) 168.3, 159.4, 143,
133.8, 131.7, 129.3, 128.2, 76.9, 71, 40.5, 26.2. MS (20 eV)
384 (M+), 327 (M+−57), 300, 222, 172, 105, 77. HRMS
(FAB), observed 385.0145 (M++1); estimated for
C15H18N2O2I, 385.0143.
Scheme 2.
Most interestingly, a control experiment confirmed that
allylTMS reacts with iodine to give iodotrimethylsilane
(ITMS). This observation is relevant in view of the
ability of ITMS to hydrodehalogenate a-haloketones.11
In the system at hand, treatment of iodoenone 4 with
1.2 equiv. of ITMS in CH2Cl2 resulted in essentially
quantitative hydrodeiodination to give the enone 3. A
plausible mechanism is presented in Scheme 2.12–15
Most salient is the apparent intermediacy of cyclic
allene 8. Although experimental and theoretical support
of the existence of (bent) 1,2-cyclohexadiene derivatives
has been reported,12 six-membered nitrogen-containing
allene 8 seems to be the first example of its kind.13
In summary, the special structural characteristics of the
perhydropyrimidinone substrate 1 lead to distinctive
reactivity upon treatment with the Sua´rez DIB/I2 decar-
boxylation protocol. Remarkable three- and five-step
tandem reactions afforded then useful enone derivatives
3 and 4.
Acknowledgements
We are indebted to CONACyT, Mexico, for financial
support via grant 33023-E and the Ca´tedra Patrimonial
de Excelencia granted to M.A.I.A.
References
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enone 3 to DIB/I2 in the same conditions described in

5300
M. A. Iglesias-Arteaga et al. / Tetrahedron Letters 43 (2002) 5297–5300
Ref. 6, resulted in a clean (61–65% yield) conversion to
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dihydro-4(H)-pyrimidin-4-one
7 was 37%. Mp 218–
220°C. [h]2D5=389.27 (c=1.0, CHCl3). 1H NMR (400
MHz, DMSO-d6, 120°C) l (ppm) 0.88 (d, J=6.6 Hz,
3H); 0.95 (d, J=6.6 Hz, 3H); 2.16 (m, 1H); 5.44 (d,
J=7.3 Hz, 1H); 7.46–7.60 (m, 6H). 13C NMR (100 MHz,
DMSO-d6, 120°C) l (ppm) 167.7, 159.4, 142.6, 133.6,
131.8, 129.2, 128.3, 120.7, 75.6, 69.7, 33.5, 18.7, 18.0. MS
(20 eV) 370 (M+), 327 (M+−43), 300, 222, 172, 105, 77.
HRMS (FAB), observed 371.0252 (M++1); estimated for
C14H16IN2O2, 371.0257.
10. Crystallographic data for this structure have been
deposited with the Cambridge Crystallographic Data
Centre as supplementary publication no. CCDC 183998.
Copies of the data can be obtained free of charge on
application to CCDC. 12 Union Road, Cambridge
CB21EZ, UK (Fax: (+44) 1223-336-036. Email:
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