Dess-Martin periodinane promoted oxidative coupling of Baylis-Hillman adducts with silyl enol ethers: A novel synthesis of cis-fused dihydropyrans

Article abstract of DOI:10.1055/s-2008-1072730

Baylis-Hillman adducts undergo smooth oxidative Mukaiyama-Michael addition and a subsequent cyclization with silyl enol ethers in the presence of Dess-Martin periodinane (DMP) and pyridine under mild reaction conditions to afford a new class of dihydropyran derivatives in good yields with high diastereoselectivity. This is the first report on the preparation of cis-fused dihydropyrans from Baylis-Hillman adducts and silyl enol ethers. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1072730

LETTER
1175
Dess–Martin Periodinane Promoted Oxidative Coupling of Baylis–Hillman
Adducts with Silyl Enol Ethers: A Novel Synthesis of cis-Fused Dihydropyrans
Synthesis
.of cis-Fused
S
D
ihydropyran
.
s
Yadav,* B. V. Subba Reddy, S. S. Mandal, A. K. Basak, C. Madavi, A. C. Kunwar
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax +91(40)27160512; E-mail: yadav@iict.res.in
Received 1 February 2008
In this article, we report a direct and one-pot method for
Abstract: Baylis–Hillman adducts undergo smooth oxidative Mu-
kaiyama–Michael addition and a subsequent cyclization with silyl
enol ethers in the presence of Dess–Martin periodinane (DMP) and
pyridine under mild reaction conditions to afford a new class of di-
the preparation of fused dihydropyrans from Baylis–Hill-
man adducts and electron-rich silyl enol ethers using
DMP and pyridine as a novel reagent system. Initially, we
hydropyran derivatives in good yields with high diastereoselectivi- attempted an oxidative Michael and a tandem cyclization
ty. This is the first report on the preparation of cis-fused
dihydropyrans from Baylis–Hillman adducts and silyl enol ethers.
of methyl 2-[hydroxy(phenyl)methyl] acrylate (1) with 1-
cyclohexenyl(1,1,1-trimethylsilyl) ether (2) in the pres-
ence of 1.2 equivalents Dess–Martin periodinane in
dichloromethane. The reaction went to completion within
two hours at room temperature; however, the cyclized
product 3a was obtained in 60% yield together with Mu-
Key words: Baylis–Hillman adducts, hypervalent iodine, enol
ethers, oxidative Mukaiyama–Michael addition
The dihydropyran ring system is frequently found in var- kaiyama–Michael adduct in 25% yield. Surprisingly,
ious natural products.1 They are normally prepared by upon addition of 1.5 equivalents of pyridine, the cyclized
means of carbonyl-Diels–Alder reaction.2 The ready product 3a was obtained exclusively in 82% yield
availability and versatility of Baylis–Hillman adducts and (Scheme 1).
their acetates makes them valuable synthetic intermedi-
OH
ates for the synthesis of a variety of heterocycles such as
OTMS
CO2Me
quinolines, pyrimidones, isoxazolines, pyrazolones, pyr-
DMP, pyridine
rolidines, indolizines, azetidinone, diazacyclophanes, and
chromanones as well as biologically active natural prod-
ucts including a-alkylidene-b-lactams, a-methylene-g-
butyrolactones and mikanecic acids, frontalin, trimethop-
rim, sarkomycin, ilmofosine nuciferol, and many oth-
ers.3,4 Consequently, various nucleophiles such as metal
hydrides, halides, azides, cyanides, alcohols, amines, are-
nes, and active methylene compounds have been used to
prepare a wide range of synthetic intermediates.5–7 How-
ever, there have been no reports on the preparation of
fused dihydropyrans from Baylis–Hillman adducts and si-
lyl enol ethers via an oxidative reaction.
+
CH2Cl2, r.t., 2 h
1a
2
TMSO
O
H
CO2Me
3a
Scheme 1 Preparation of product 3a
In recent years, hypervalent iodine reagents have occu-
pied an important place in the reactions of natural and syn-
thetic organic chemistry because of their potential
applications in the construction of carbon–carbon and car-
bon–heteroatom bonds.8 One of the most significant ad-
vances in the field, discovery of the Dess–Martin
periodinane (DMP) reagent, opened the door to a mild ox-
idation procedure allowing alcohols to be converted into
the corresponding carbonyl compounds.9 Its widespread
use over the past decade attests to its benign nature and its
ability to succeed under mild oxidation circumstances.
The Dess–Martin periodinane is an oxidizing agent that
overcomes many of the disadvantages associated with ox-
idative methods developed so far.10
The product 3b was thoroughly studied using various
NMR techniques including H-decoupling experiments,
1
double-quantum-filtered correlation spectroscopy (DQF-
COSY), nuclear Overhauser effect spectroscopy (NOE-
SY) and heteronuclear single-quantum correlation
spectroscopy (HSQC). Though four protons in between
1.83–2.69 ppm were easily noticed, which contained the
resonances from the allylic protons at C6 as well, other
seven proton resonances crowded a region of about 0.37
ppm (between 1.28 to 1.65 ppm), resulting in extensive
overlap. Resonances of the five methylene proton pairs in
the molecule could be easily observed with the help of
HSQC experiments. Once these protons were located, the
assignments were carried out with the help of the splitting
patterns, coupling constants as well as the DQFCOSY and
NOESY experiments. For the cyclohexane ring fused to
oxygen containing six-membered ring, all the characteris-
SYNLETT 2008, No. 8, pp 1175–1178
x
x.
x
x.
2
0
0
8
Advanced online publication: 16.04.2008
DOI: 10.1055/s-2008-1072730; Art ID: D03608ST
© Georg Thieme Verlag Stuttgart · New York

1176
J. S. Yadav et al.
LETTER
1
tic signatures of a C4 chair form are observed from the This result encouraged us to examine other substituted
NMR spectra. Emphatic support comes from couplings, Baylis–Hillman adducts (Table 1). Interestingly, this
3
3
3JH1a–H2a = ca. 12.8 Hz, JH1a–H2e = 3.8 Hz, JH1e–H2a = ca. method worked well with substrates derived from both al-
3.6 Hz, 3JH1e–H2e = ca. 3.6 Hz, 3JH2a–H3a = ca. 12.6 Hz, 3JH2a– iphatic and aromatic aldehydes. As with cyclohexenyl(tri-
H3e = ca. 3.5 Hz, 3JH3a–H4a = ca. 12.3 Hz, 3JH3e–H4a = 3.2 Hz, methylsilyl) ether, other silyl enol ethers derived from
3
3JH4a–H5 = 10.5 Hz, JH4e–H5 = 4.2 Hz, and 1, 3-diaxial acetophenone and cyclopentanone also reacted readily
NOE enhacement, H1a/H3a, H1a/H5a and H3a/H5a. Fur- with Baylis–Hillman adducts under the influence of DMP
thermore, the SiCH3/H1a and SiCH3/H1e NOE cross and pyridine. The cis-fused dihydropyran was formed ex-
peaks, provide evidence for O–C(Si) bond in an equatorial clusively in each reaction, the structure of which has been
orientation in the cyclohexane ring, thus confirming the confirmed by NOE studies. However, silyl enol ethers un-
cis fusion of the two six-membered rings. In addition, the derwent exclusively Mukaiyama–Michael addition with
presence of a Ph group adjacent to oxygen is confirmed by Baylis–Hillman adducts when using 1.2 equivalents of
NOE correlations for Ph/SiCH3. Further support comes IBX in DMF (Scheme 2).
from energy-minimized structure (Figure 1).
OTMS
OH
CO2Me
IBX, DMF
+
r.t., 2 h, 81%
Cl
O
CO2Me
Cl
O
Figure 1 The characteristic NOEs and energy-minimized structure
of 3b
4
Scheme 2 Preparation of product 4
Table 1 Preparation of cis-Fused Dihydropyrans from Baylis–Hillman Adducts and Silyl Enol Ethers Promoted by DMP and Pyridine
Entry Baylis–Hillman adduct 1
Enol ether 2
Product 3a
Time (h) Yield (%)b
TMSO
O
OTMS
OH
CO2Me
a
2.0
2.0
3.0
82
80
78
MeO2C
TMSO
O
OTMS
OTMS
OH
CO2Et
b
EtO2C
Me
TMSO
OH
O
CO2Et
c
Me
EtO2C
TMSO
O
OH
OTMS
OTMS
CN
d
3.0
2.0
79
84
MeO
MeO
NC
TMSO
O
OH
CO2Me
e
F
F
MeO2C
Synlett 2008, No. 8, 1175–1178 © Thieme Stuttgart · New York

LETTER
Synthesis of cis-Fused Dihydropyrans
1177
Table 1 Preparation of cis-Fused Dihydropyrans from Baylis–Hillman Adducts and Silyl Enol Ethers Promoted by DMP and Pyridine
(continued)
Entry Baylis–Hillman adduct 1
Enol ether 2
Product 3a
Time (h) Yield (%)b
OH
TMSO
O
OTMS
CO2Me
f
3.0
82
OPh
MeO2C
PhO
Cl
TMSO
OH
OTMS
O
CO2Me
g
2.0
6.0
3.0
81
78
78
Cl
MeO2C
TMSO
O
OTMS
OTMS
OH
h
i
CO2Me
MeO2C
TMSO
OH
O
CO2Et
Me
Me
EtO2C
TMSO
O
OH
OTMS
OTMS
CO2Me
j
2.0
3.0
2.0
80
79
86
MeO2C
TMSO
O
OH
OH
CN
k
l
Cl
Cl
Cl
Cl
NC
TMSO
O
OTMS
CO2Me
MeO2C
a All products were characterized by 1H NMR, IR, and mass spectroscopy.
b Yield refers to pure products after chromatography.
In all cases, the reactions were clean and afforded the Table 1.11 The reaction most likely proceeds via an initial
Michael adducts in good yields. The reaction conditions DMP oxidation of Baylis–Hillman adducts and then Mu-
were compatible with various functionalities such as ha- kaiyama–Michael addition with silyl enol ethers and a
lides, nitriles, aryl methyl ethers, esters, and alkenes subsequent cyclization to afford the product (Scheme 3).
1
(Table 1). All the products were characterized by H
A similar type of cyclization was reported previously to
NMR, IR, and mass spectrometry. Of the various hyper-
valent iodine reagents examined, including iodosoben-
prepare cis-fused pyranopyrrole derivatives via an in-
verse-electron-demand hetero-Diels–Alder reaction.12
zene (PhIO), iodobenzene diacetate [PhI(OAc)2], and 2-
In conclusion, we have described a one-pot oxidative
iodoxybenzoic acid (IBX), Dess–Martin periodinane
Michael addition and a tandem cyclization of Baylis–Hill-
(DMP) was found to be the best in terms of conversion.
man adducts with silyl enol ethers using DMP and pyri-
dine as a novel reagent system. The method offers several
advantages such as high regioselectivity, operational sim-
plicity, mild reaction conditions, cleaner reaction profiles,
simple workup procedure, and the use of readily available
reagents which makes it a useful and attractive strategy
Other oxidants such as Oxone®, CAN, MnO2, and KBrO3
failed to produce the desired product. As solvent, dichlo-
romethane gave the best results. The scope of the DMP-
and pyridine-promoted oxidative tandem reaction was in-
vestigated with respect to various Baylis–Hillman adducts
and silyl enol ethers, and the results are presented in
Synlett 2008, No. 8, 1175–1178 © Thieme Stuttgart · New York

1178
J. S. Yadav et al.
LETTER
(9) (a) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
(b) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113,
7277.
(10) (a) Nicolaou, K. C.; Baran, P. S.; Zong, Y.-L.; Sugita, K.
J. Am. Chem. Soc. 2002, 124, 2212. (b) Nicolaou, K. C.;
Mathison, C. J. N. Angew. Chem. Int. Ed. 2005, 44, 5992.
(c) Chaudhari, S. S. Synlett 2000, 278. (d) Ladziata, U.;
Zhdankin, V. V. ARKIVOC 2006, (ix), 26. (e) Lawrence, J.
N.; Crump, J. P.; McGown, A. T.; Hadfield, J. A.
Tetrahedron Lett. 2001, 42, 3939.
..
Ph
OH
DMP
TMSO
Ph
O
+
MeO2C
MeO2C
+
+
OTMS
O-TMS
O
Ph
OH
Ph
..
MeO2C
(11) General Experimental Procedure
MeO2C
A mixture of Baylis–Hillman adduct (1 mmol), DMP (1.2
mmol), and pyridine (1.5 mmol) in anhyd CH2Cl2 (10 mL)
was stirred at r.t. until complete oxidation took place. To
this, trimethylsilyl enol ether (1.5 mmol) was added and
stirred until complete addition (as indicated by TLC) took
place. The reaction mixture was diluted with H2O (50 mL)
and extracted with Et2O (3 × 15 mL). The combined ether
layer was washed with sat. aq NaHCO3 soln (1 × 15 mL),
brine (1 × 10 mL), dried over Na2SO4, and evaporated. The
crude product was purified by silica gel column
chromatography using a gradient mixture of hexane–EtOAc
(9:1) as eluent to afford pure substituted dihydropyran
derivatives.
OTMS
Ph
O
MeO2C
Scheme 3 A plausible reaction mechanism
for the preparation of highly functionalized dihydropyr-
ans in a single-step operation.
Spectral Data of Selected Compounds
Compound 3a (Table 1): colorless liquid. IR (KBr): nmax
=
2954, 2838, 1738, 1454, 1234, 1207, 1153, 1017, 781 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.0 (s, 9 H), 1.20–1.58 (m,
8 H), 1.61–1.76 (m, 1 H), 2.06 (dd, 1 H, J = 1.4, 16.4 Hz),
2.56 (dd, 1 H, J = 5.8, 16.8 Hz), 3.32 (s, 3 H), 7.14–7.18 (m,
5 H). ESI-MS: m/z = 361 [M + 1], 383 [M + Na]. HRMS:
m/z calcd for C20H28O4NaSi: 383.1654; found: 383.1641.
Compound 3b (Table 1): 1H NMR (600 MHz, CDCl3): d =
7.33 (m, 5 H, Ph), 3.92 (q, 2 H, J = 7.2 Hz, OCH2), 2.72 (dd,
1 H, J = 16.7, 6.2 Hz, H6), 2.23 (dd, 1 H, J = 16.7, 2.0 Hz,
H6¢), 2.12 (dt, 1 H, J = 13.0, ca. 3.6 Hz, H1e), 1.85 (dddd, 1
H, J = 10.5, 6.2, 4.2, 2.0 Hz, H5a), 1.65 (m, 1 H, H3e), 1.62
(m, 1 H, H2e), 1.57 (m, 1 H, H4e), 1.55 (dt, 1 H, J = 3.8, ca.
12.8 Hz, H1a), 1.44 (tq, 1 H, J = ca. 3.5, ca. 12.6 Hz, H2a),
1.34 (dq, 1 H, J = 3.2, ca. 12.3 Hz, H4a), 1.28 (m, 1 H, H3a).
0.91 (t, J = 7.2 Hz, 1 H, CH3), 0.15 (s, 9 H, 3 × CH3).
References and Notes
(1) (a) Faulkner, D. J. Nat. Prod. Rep. 2000, 17, 7. (b) Roush,
W. R.; Dilley, G. J. Synlett 2001, 955. (c) Norcross, R. D.;
Paterson, I. Chem. Rev. 1995, 95, 2041. (d) Paterson, I.; De
Savi, C.; Tudge, M. Org. Lett. 2001, 3, 3149.
(2) (a) Jørgensen, K. A. Angew. Chem. Int. Ed. 2000, 112, 3702.
(b) Johnson, J. S.; Evans, D. A. Acc. Chem. Res. 2000, 33,
325. (c) Jørgensen, K. A.; Johannsen, M.; Yao, S.; Audrain,
H.; Thorhauge, J. Acc. Chem. Res. 1999, 32, 605.
(d) Gademann, D. E.; Chavez, D. E.; Jacobsen, E. N. Angew.
Chem. Int. Ed. 2002, 112, 3702.
(3) Baylis, A. B.; Hillman, M. E. D. DE 2155113, 1972; Chem.
Abstr. 1972, 77, 34174q.
(4) (a) Basavaiah, D.; Rao, A. J.; Satyanarayana, T. Chem. Rev.
2003, 103, 811. (b) Basavaiah, D.; Dharma Rao, P.;
Suguna Hyma, R. Tetrahedron 1996, 52, 8001. (c) Drewes,
S. E.; Roos, G. H. P. Tetrahedron 1988, 44, 4653.
(5) (a) Lee, K. Y.; Kim, J. M.; Kim, J. N. Tetrahedron Lett.
2003, 44, 6737. (b) Lee, K. Y.; Kim, J. M.; Kim, J. N.
Tetrahedron 2003, 59, 385. (c) Im, Y. J.; Lee, K. Y.; Kim, T.
H.; Kim, J. N. Tetrahedron Lett. 2002, 43, 4675. (d) Kim, J.
N.; Kim, J. M.; Lee, K. Y. Synlett 2003, 821. (e) Kim, J. N.;
Kim, H. S.; Gong, J. H.; Chung, Y. M. Tetrahedron Lett.
2001, 42, 8341.
(6) (a) Drewes, S. E.; Emslie, N. D. J. Chem. Soc., Perkin Trans.
1 1982, 2079. (b) Hoffmann, H. M. R.; Rabe, J. Helv. Chim.
Acta 1984, 67, 413. (c) Hoffmann, H. M. R.; Rabe, J. J. Org.
Chem. 1985, 50, 3849.
(7) (a) Hoffmann, H. M. R.; Rabe, J. Angew. Chem., Int. Ed.
Engl. 1985, 24, 94. (b) Buchholz, R.; Hoffmann, H. M. R.
Helv. Chim. Acta 1991, 74, 1213. (c) Ameer, F.; Drewes, S.
E.; Hoole, R. F. A.; Kaye, P. T.; Pitchford, A. T. J. Chem.
Soc., Perkin Trans. 1 1985, 2713.
Compound 3f (Table 1): colorless liquid. IR (KBr): nmax
=
3029, 2948, 2865, 1718, 1495, 1265, 1217, 1137, 1037, 854
cm–1. 1H NMR (300 MHz, CDCl3): d = 0.0 (s, 9 H), 1.80
(ddd, 1 H, J = 1.8, 5.6, 13.4 Hz), 2.21 (ddd, 1 H, J = 3.5, 5.4,
13.4 Hz), 2.52 (ddd, 1 H, J = 3.5, 5.6, 16.9 Hz), 2.66 (ddd, 1
H, J = 5.4, 11.3, 16.8 Hz), 3.59 (s, 3 H), 7.07–7.13 (m, 5 H),
7.22 (td, 1 H, J = 1.1, 7.9 Hz), 7.3–7.43 (m, 6 H), 7.50 (dd, 2
H, J = 1.5, 7.7 Hz). HRMS: m/z calcd for C28H31O5Si:
475.1940; found: 475.1954.
Compound 3h (Table 1): colorless liquid. IR (KBr): nmax
2928, 2857, 1715, 1504, 1433, 1151, 1039, 754 cm–1. 1H
NMR (300 MHz, CDCl3): d = 0.0 (s, 9 H), 0.78 (t, 3 H,
=
J = 6.8 Hz), 1.10–1.27 (m, 6 H), 1.33–1.72 (m, 6 H), 1.86–
2.02 (m, 1 H), 2.07 (dd, 1 H, J = 6.0, 12.0 Hz), 2.16 (dd, 1 H,
J = 6.0, 12.0 Hz), 3.55 (s, 3 H).
Compound 4 (Scheme 2): colorless liquid. IR (KBr): nmax
=
2920, 2851, 1739, 1683, 1506, 1443, 1226, 1157, 1019, 755
cm–1. 1H NMR (300 MHz, CDCl3): d = 2.20–2.39 (m, 2 H),
2.94–3.19 (m, 2 H), 3.61 (s, 3 H), 4.67 (dd, 1 H, J = 6.0, 7.5
Hz), 7.33–7.52 (m, 5 H), 7.87 (d, 2 H, J = 7.5 Hz), 7.99 (d, 2
H, J = 9.0 Hz). ESI-MS: m/z = 345 [M + 1], 367 [M + Na].
HRMS: m/z calcd for C19H17O4NaCl: 367.0713; found:
367.0715.
(8) (a) Varvoglis, A. Hypervalent Iodine in Organic Synthesis;
Academic Press: San Diego, 1997, 256. (b) Wirth, T.; Hirt,
U. H. Synthesis 1999, 1271. (c) Wirth, T. Angew. Chem. Int.
Ed. 2001, 40, 2812.
(12) Horiguchi, Y.; Sano, T.; Tsuda, Y. Chem. Pharm. Bull.
1996, 44, 670.
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