BiBr3-initiated tandem addition/silyl-prins reactions to 2,6-disubstituted dihydropyrans

Article abstract of DOI:10.1021/jo060738k

A tandem addition/silyl-Prins reaction efficiently affords cis-2,6-disubstituted dihydropyrans (DHPs) using 5 mol % of BiBr₃ in CH₂Cl₂. The reaction occurs between δ- triethylsilyloxyvinyltrimethylsilanes and a variety of

Full text of DOI:10.1021/jo060738k

synthesis of 2,6-disubstituted dihydropyrans (DHPs) using 5 mol
% of BiBr3 as an initiator for tandem addition/silyl-Prins
cyclization reactions. We also present a three-component, one-
pot variation of this reaction to provide a functionalized DHP.
BiBr3-Initiated Tandem Addition/Silyl-Prins
Reactions to 2,6-Disubstituted Dihydropyrans
Yajing Lian and Robert J. Hinkle*
Cyclic ethers are widespread in nature, and a variety of
substitution patterns are present in tetrahydropyran subunits. The
related 2,6-disubstituted dihydropyran ring system is also
prevalent. Not only are these latter ethers present in many natural
products, such as scytophycin C,6 but they are also synthetically
useful intermediates in the production of polysubstituted tet-
rahydropyran ring systems, such as those found in the pseudomon-
ic acids.7 Many common approaches8,9 have been reported
toward dihydropyrans, and some of the more varied methodolo-
gies include addition of organozinc reagents to 1,2-dihydropy-
rans,10 base-promoted cyclizations of disulfinyl dienols,11 olefin
metathesis,12 Prins cyclizations of cyclopropyl carbinols,13 or
homoallylic alcohols,14 and an intramolecular silyl-modified
Sakurai reaction (ISMS).15 Many of these reactions have
limitations, such as the need for strictly anhydrous conditions,
stoichiometric quantities of Lewis acid initiator, or delivery of
a strong Lewis acid at low temperature.
Department of Chemistry, The College of William and Mary,
P.O. Box 8795, Williamsburg, Virginia 23187-8795
rjhink@wm.edu
ReceiVed April 6, 2006
A recent silyl-Prins alternative was described by Dobbs and
co-workers16 and utilized 4-trimethylsilyl-3-butenols to react
with aldehydes under InCl3-initiated conditions to obtain dihy-
dropyran units in good yields with high diastereoselectivities
for the cis-isomers. These authors typically used 0.5-1.0 equiv
of InCl3 for reactions of homoallylic silanes and aldehydes, and
none of their examples included reactions with aryl-substituted
homoallylic silanes. Although the toxicity data for InCl3 have
not been established, it is under investigation as a mutagen and
is significantly more expensive per mole than BiBr3.17,18
A tandem addition/silyl-Prins reaction efficiently affords cis-
2,6-disubstituted dihydropyrans (DHPs) using 5 mol % of
BiBr3 in CH2Cl2. The reaction occurs between δ-triethyl-
silyloxyvinyltrimethylsilanes and a variety of aldehydes to
give good to excellent isolated yields of DHPs. The diaste-
reoselectivities in the crude products are significantly affected
by aldehyde substitution with electron-rich aldehydes, pro-
viding 2-3:1 (cis:trans) and neutral (or electron-poor)
aldehydes affording dr g 19:1 (cis:trans).
(6) Roush, W. R.; Dilley, G. J. Synlett 2001, SI, 955-959.
(7) Class, Y. J.; DeShong, P. Chem. ReV. 1995, 95, 1843-1857.
(8) Recent reviews of synthetic methods toward a number of natural
products containing cyclic ethers: (a) Yeung, K.-S.; Paterson, I. Chem. ReV.
2005, 105, 4237-4313. (b) Nakata, T. Chem. ReV. 2005, 105, 4237-4313.
(c) Dieters, A.; Martin, S. F. Chem. ReV. 2004, 104, 2199-2238. (d) Faul,
M. M.; Huff, B. E. Chem. ReV. 2000, 100, 2407-2474.
(9) For a variety of methods for the synthesis of dihydropyran ring
systems, see: (a) Morris, W. J.; Custar, D. W.; Scheidt, K. A. Org. Lett.
2005, 7, 1113-1116. (b) Lowe, J. T.; Panek, J. S. Org. Lett. 2005, 7, 1529-
1532. (c) Evans, P. A.; Lawler, M. J. Am. Chem. Soc. 2004, 126, 8642-
8643. (d) Viswanathan, G. S.; Yang, J.; Li, C. Org. Lett. 1999, 1, 993-
995. (e) Vares, L.; Rein, T. J. Org. Chem. 2002, 67, 7226-7237. (f) Brimble,
M. A.; Pavia, G. S.; Stevenson, R. J. Tetrahedron Lett. 2002, 43, 1735-
1738. (g) Semeyn, C.; Blaauw, R. H.; Hiemstra, H.; Speckamp, W. N. J.
Org. Chem. 1997, 62, 3426-3427.
Recently, bismuth compounds have gained popularity as
convenient, inexpensive, and environmentally benign1 Lewis
acids2,3 and have become intensively studied catalysts in organic
synthesis.4 Many of the reactions that bismuth compounds
initiate are simple silyl protection and deprotection sequences,
but bismuth can also be used in the synthesis of tetrahydropyran
derivatives by using a silyl-protected alcohol tethered to an
aldehyde and/or ketone electrophile.5 On the basis of the
chemistry involving vinyltrimethylsilane as a nucleophile to
attack an incipient oxocarbenium ion (i.e., the silyl-Prins
reaction), we now report a mild, convenient, and efficient
(10) Steinhuebel, D. P.; Fleming, J. J.; Du Bois, J. Org. Lett. 2002, 4,
293-295.
(11) de la Pradilla, R. F.; Tortosa, M. Org. Lett. 2004, 6, 2157-2160.
(12) Wildemann, H.; Du¨nkelmann, P.; Mu¨ller, M.; Schmidt, B. J. Org.
Chem. 2003, 68, 799-804.
(1) The LD50 of BiCl3 is listed as 3334 mg/kg (oral, rat) in the MSDS
provided by Sigma-Aldrich Chemical Corporation, St. Louis, MO.
(2) Compelling spectroscopic evidence for the role of Bi(OTf)3 as a Lewis
acid catalyst in a hydroamination reaction was recently described: Quin,
H.; Yamagiwa, N.; Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc. 2006,
128, 1611-1614.
(3) Ollevier, T.; Nadeau, E. J. Org. Chem. 2004, 69, 9292-9295.
(4) (a) Komatsu, N. In Organobismuth Chemistry; Suzuki, H., Matano,
Y., Eds.; Elsevier: New York, 2001; pp 371-440. (b) Leonard, N. M.;
Wieland, L. C.; Mohan, R. S. Tetrahedron 2002, 58, 8373-8397. (c)
Gaspard-Iloughmane, H.; Le Roux, C. Eur. J. Org. Chem. 2004, 2517-
2532.
(13) Yadav, V.; Kumar, N. V. J. Am. Chem. Soc. 2004, 126, 8652-
8653.
(14) Chan, K.-P.; Loh, T.-P. Org. Lett. 2005, 7, 4491-4494.
(15) (a) Marko´, I. E.; Bayston, D. J. Tetrahedron 1994, 50, 7141-7156.
(b) Marko´, I. E.; Dobbs, A. P.; Scheirmann, V.; Chelle´, F.; Bayston, D. J.
Tetrahedron Lett. 1997, 34, 2899-2902.
(16) (a) Dobbs, A. P.; Martinovic´, S. Tetrahedron Lett. 2002, 43, 7055-
7057. (b) Dobbs, A. P.; Guesne´, S. J.; Martinovic´, S.; Coles, S.; Hursthouse,
M. B. J. Org. Chem. 2003, 68, 7880-7883.
(17) According to the 2005-2006 general Aldrich catalog, InCl3 costs
$2,092 per mole, whereas BiBr3 costs $393 per mole; Aldrich Chemical
Corporation, Milwaukee, WI.
(5) (a) Evans, P. A.; Cui, J.; Gharpure, S. J.; Hinkle, R. J. J. Am. Chem.
Soc. 2003, 125, 11456-11457. (b) Hinkle, R. J.; Lian, Y.; Litvinas, N. D.;
Jenkins, A. T.; Burnette, D. C. Tetrahedron 2005, 61, 11679-11685.
(18) MSDS number I1680, Mallinckrodt Baker, Inc., Phillipsburg, NJ
08865.
10.1021/jo060738k CCC: $33.50 © 2006 American Chemical Society
Published on Web 08/09/2006
J. Org. Chem. 2006, 71, 7071-7074
7071

TABLE 2. Synthesis of Disubstituted Dihydropyrans
We initially investigated the reaction of simple (Z)-1-
trimethylsilyl-4-triethylsilyloxybutene, 1a, with benzaldehyde
to establish the feasibility of our approach to dihydropyran
systems (eq 1).
silane 1,
aldehyde
R2
dr (GC,
yield
(%)c
entrya
product
R1
cis/trans)b
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
2g
2h
2i
H
Ph-
74
70
74
58
97
88
98
55
82
47
94
n-C5H11-
n-C5H11-
n-C5H11-
n-C5H11-
n-C5H11-
n-C5H11-
Ph
Ph
Ph
Ph
Ph-
>99:1
73:1
p-CF3Ph-
p-MeOC6H4-
PhCH2-
i-Pr-
o-CHOPh-
Ph-
p-CF3Ph-
p-MeOC6H4-
PhCH2-
2-3:1d
45:1
We were gratified to observe that 5 mol % of BiBr3 efficiently
catalyzed this reaction and afforded 74% isolated yield of the
desired product. Lower quantities of BiBr3 led to significantly
slower conversions. Furthermore, the synthesis was conveniently
conducted at room temperature in distilled CH2Cl2. In contrast
to our result, the corresponding InCl3 reaction (1.0 equiv)16a
resulted in a significantly lower yield (39%) using benzaldehyde
as the electrophile. The poor reactivity of benzaldehyde has also
been documented by others in their syntheses of DHP ring
systems.9d,19
>99:1
>99:1
4-5:1
>99:1
2-3:1d
35:1
10
11
2j
2k
a All the reactions were carried on 0.5 mmol scale in 5.0 mL of CH2Cl2
at room temperature using 2.0 equiv of the corresponding aldehyde.
b Diastereomeric ratios were determined by capillary GC analysis of crude
reaction mixtures. c Isolated yield of pure cis-isomers only, after flash
column chromatography. d Diastereomeric ratios were determined by 1H
NMR analysis of crude reaction mixtures.
TABLE 1. Optimization for the Synthesis of
2-Pentyl-6-phenyl-3,6-dihydro-2H-pyran
(entries 5 and 6, respectively) resulted in lower isolated yields
of the desired product. All of the reactions with different acids
provided the cis-isomers with high selectivity (>99:1 by GC).
Of the acids presented in Table 1, the BiBr3 or commercially
available HCl in dioxane are the most convenient and operation-
ally simple. TMSOTf and TiCl4 are extremely hygroscopic, and
BF3•OEt2 is typically distilled immediately prior to use and
dispensed by syringe. Finally, the latter three acids examined
are normally used at low temperature in strictly anhydrous CH2-
Cl2.
entryb
acid
conditions
rt
rt
rt
-78 °C to rt
-78 °C to rt
-78 °C to rt
yield (%)c
1
2
3
4
5
6
5% of BiBr3
5% of BiBr3
70
55
45
18
60
54
d
10% of HCle
5% of TiCl4
10% of BF3‚OEt2
10% of TMSOTf
Encouraged by the success with the acid studies and the
unsubstituted vinylsilane, we turned our attention to examining
different substituents on the homoallylic vinylsilane and alde-
hyde components (Table 2). Both aliphatic (entries 2-7)- and
aromatic (entries 8-11)-substituted vinylsilanes were effective
substrates, reacting smoothly to provide the expected cis-
dihydropyrans in good to excellent isolated yields after column
chromatography. The remainder of the cis-DHP products were
produced in 55-98% isolated yields, and the cis-stereochemistry
for all products were verified by qualitative NOE enhancements
of the methine hydrogens flanking the oxygen atom.21
a Diastereomeric ratios were verified by capillary GC analysis of crude
reaction mixtures. b All reactions were carried on 0.5 mmol scale in 5.0
mL of distilled CH2Cl2 at room temperature using 2.0 equiv of benzaldehyde.
c Isolated yield of pure cis-isomers only, after flash column chromatography.
d The reaction was carried in 5.0 mL of CH3CN instead of CH2Cl2.
e
Reactions with BiCl3 were comparable to those with BiBr3. See ref 20.
We then extended this reaction to homoallylic silanol 1b (eq
2 and Table 1) to determine the stereoselectivity of the tandem
addition/silyl-Prins reaction. Under conditions optimized for 1a,
we observed only a single diastereomer for the product as
1
indicated by GC and H NMR spectroscopy. Qualitative NOE
measurements21 established the cis-stereochemistry, and only a
very minor amount (<1%) of the presumed trans-diastereomer
was detected by capillary GC analysis of crude reaction
mixtures. We then compared this result to the same reaction
mediated by other common catalysts (Table 1).
SCHEME 1. Possible Intermediates in Silyl-Prins
Cyclizations
Considering that 1 mol of BiBr3 might generate 2 mol of
HBr by hydrolysis with adventitious water, we doubled the
relative quantities of commercially available Lewis acids as well
as the quantity of anhydrous Brønsted acid, HCl (10%).20 It is
significant to note that conducting the reaction in CH2Cl2 (entry
1) rather than distilled CH3CN (entry 2) was beneficial, and
use of the more common Lewis acids, TMSOTf and BF3•OEt2
(19) (a) Marko´, I. E.; Bayston, D. J. Tetrahedron Lett. 1993, 34, 6595-
6598.
(20) BiCl3 is equally effective for the reactions herein, but HBr was not
available as a nonaqueous solution for control experiments. We chose to
utilize the quantities of BiBr3 on hand for the remainder of the reactions.
(21) See the Supporting Information.
The general, observed cis-stereoselectivity can be explained
by the formation of initial (E)-oxocarbenium ion, A (Scheme
1). In A, the two groups adjacent to the oxygen atom occupy
the pseudoequatorial positions to eliminate diaxial interactions,
7072 J. Org. Chem., Vol. 71, No. 18, 2006

min at room temperature, but during the early part of the
reaction, the amount of trans-2d product exceeded that of the
cis-compound, cis-2d. During the 40 h of monitoring, the trans-
diastereomer isomerized to the more thermodynamically stable
cis-isomer under the reaction conditions. For this particular
aldehyde, we propose that the unexpected trans-diastereomer
is the kinetic product, and this isomerizes to the cis-isomer under
the reaction conditions. This surely involves a resonance-
stabilized benzylic cation.21 In terms of the mechanistic
pathways shown in Scheme 1, p-anisaldehyde proceeds through
the (Z)-oxocarbenium ion, A′. Due to the stabilizing effect of
the p-methoxy group on the ion, intermediate A′ would not be
prone to oxonia-Cope rearrangement to the less stable oxocar-
benium ion, B′, and direct cyclization from A′ would rapidly
afford the trans-product. It should be noted that even for
somewhat hindered aliphatic aldehyde electrophiles (e.g., entries
5, 6, and 11) cis-diastereoselectivity is significantly higher.
Therefore, the origin of the unusual kinetic preference for the
trans-product likely involves both steric and electronic factors.
The low diastereoselectivity for product 2h (entry 8; R1 ) R2
) Ph) is anomalous. Efforts to elucidate the origin of the
selectivities are underway and will be reported in due course.27
Reaction of vinylsilane 1b with phthaldehyde only provided
2-(6-pentyl-5,6-dihydro-2H-pyran-2-yl)benzaldehyde, 2g, in 98%
isolated yield (Table 2, entry 7). Due to the general entropic
preference for intramolecular reactions when phthaldehyde reacts
with other nucleophiles, such as allyltrimethylsilane, we believed
that reaction of both aldehydes might provide an isobenzofuran
derivative.28 Under BiBr3 and vinyltrimethylsilane conditions,
however, only one carbonyl group participated in the reaction
and no isobenzofuran was detected. This selectivity is powerful
because the remaining carbonyl group can be used for further
elaboration.
Finally, Le Roux and co-workers reported the BiCl3-catalyzed
Mukaiyama aldol reaction between silyl enol ethers and
aldehydes in CH2Cl2.29 Combining the silyl-Prins cyclization
described herein and the Mukaiyama aldol would provide an
extremely expedient route toward functionalized cis-2,6-disub-
stituted dihydropyran systems. We chose to investigate the
Mukaiyama aldol reaction between â,γ-unsaturated aldehyde,
1d, and commercially available methyl â,â-dimethylketenetri-
methylsilyl acetal (eq 4). The initial aldol was accomplished at
room temperature in the presence of 10 mol % of BiBr3 in CH2-
Cl2. Once aldehyde 1d was consumed (ca. 2 h), phenylacetal-
dehyde (2 equiv) and 10% additional BiBr3 were added to the
same flask, and the reaction mixture was stirred until the
intermediate aldol adduct was consumed (TLC). Isolation by
column chromatography afforded dihydropyran 3 in 64% overall
isolated yield. This yield is remarkable given the fact that
aldehyde 1d is unstable and could not be purified before use.
FIGURE 1. Correlation between reaction time and diastereoselectivity
(trans/cis) for 2d (Table 2, entry 4). The reaction was carried in 0.1
mmol scale in 1.0 mL of CDCl3, using 5% BiBr3 as catalyst and 2.0
equiv of anisaldehyde. The CDCl3 was passed through MgSO4 and
basic Al2O3 to eliminate trace water and acid in CDCl3 solvent. The
reaction was complete in ca. 110 min, according to the consumption
of the vinyltrimethylsilane.
whereas the TMS moiety is oriented axially to allow greater
stabilization of the cation that develops â to the silane.
Stabilization is much more effective than if the TMS were in
the equatorial position.9g,22 A [3,3] sigmatropic oxonia-Cope
rearrangement could then occur from A to afford oxocarbenium
ion, B.23,24 Direct attack on the oxocarbenium carbon by the
π-electrons via either A or B and subsequent desilylation would
then provide the observed cis-DHP products. For intermediates
that contain electron-donating groups for R1 and R2, oxonia-
Cope reactions should be facile, both A and B would be present,
and either intermediate would lead to the cis-diastereomer
through the same secondary â-silyl cation. Formation of the
stereoisomeric (Z)-oxocarbenium ion25 (A′) would provide an
alternative pathway and lead to the corresponding trans-
products. In A′, R2 is oriented trans to both the axial TMS
moiety and R1, which relieves steric and/or electronic interac-
tions with the axial TMS.
Compared to aliphatic aldehydes, the use of aromatic
analogues sometimes resulted in more complex reaction mix-
tures and lower isolated yields. Whereas introduction of the
electron-withdrawing -CF3 moiety increased yields, the pres-
ence of electron-donating groups decreased the yields (entries
2-4 and 5-8). Electron-rich p-anisaldehyde generally provides
lower yields in such reactions,9a,26 or the yields are not reported.
Under the BiBr3 conditions reported herein, the crude material
showed a 2-3:1 diastereoselectivity, and the isolated yield of
pure cis-2j (entry 10) was moderate (47%); the corresponding
trans-isomer was contaminated with an inseparable, unidentified
byproduct.
Intrigued by the low selectivity for 2d, we followed the
progress of the reaction of p-anisaldehyde and vinylsilane, 1b
by 1H NMR spectroscopy in CDCl3 at room temperature (Figure
1). The p-anisaldehyde electrophile was consumed within 110
(22) (a) Castro, P.; Overman, L. E. Tetrahedron Lett. 1993, 34, 5243-
5246. (b) Daub, G. W.; Heerding, D. A.; Overman, L. E. Tetrahedron 1988,
44, 3919-3930. (c) Blumenkopf, T. A.; Overman, L. E. Chem. ReV. 1986,
86, 857-873.
(23) Oxonia-Cope reactions are well documented in Prins cyclizations.
For a lead reference, see: Jasti, R.; Anderson, C. D.; Rychnovsky, S. D. J.
Am. Chem. Soc. 2005, 127, 9939-9945.
(24) Castro, A. M. M. Chem. ReV. 2004, 104, 2939-3002.
(25) The (Z)-oxocarbenium ion recently has been suggested as an
intermediate for isomerization in the solvolysis of tetrahydropyranyl
mesylates. See ref 23.
(26) Crosby, S. R.; Harding, J. R.; King, C. D.; Parker, G. D.; Willis, C.
L. Org. Lett. 2002, 4, 577-580.
In summary, we have demonstrated a rapid synthesis of cis-
2,6-disubstituted dihydropyrans in high yield and good selectiv-
ity by using 5 mol % of BiBr3 as a mild and environmentally
J. Org. Chem, Vol. 71, No. 18, 2006 7073

(m, 1H), 3.80 (s, 3H), 3.68-3.75 (m, 1H), 1.99-2.15 (m, 2H),
1.25-1.70 (m, 8H), 0.89 (t, J ) 6.8 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 159.2(e), 134.1(e), 130.4(o), 128.7(o), 125.0(o), 114.0-
(o), 77.4(o), 74.8(o), 55.6(o), 36.4(e), 32.2(e), 31.3(e), 25.5(e), 23.0-
(e), 14.5(o). Anal. Calcd for C17H24O (260.37): C, 78.42; H, 9.29.
Found: C, 78.16; H, 9.49.
benign catalyst or initiator. Aliphatic as well as aromatic
aldehydes are effective for this silyl-Prins reaction, although
electron-rich aromatic aldehydes resulted in diminished yields.
Use of phthaldehyde as an electrophile afforded a functionalized
product, 2-(6-pentyl-5,6-dihydro-2H-pyran-2-yl)benzaldehyde in
nearly quantitative yield. We also present a one-pot, three-
component reaction involving an initial BiBr3-mediated Mu-
kaiyama aldol followed by a silyl-Prins cyclization. These
Bi(III)-initiated protocols toward disubstituted dihydropyrans
represent extremely mild and convenient alternatives to reactions
with other Lewis acids such as BF3•Et2O or TMSOTf. We are
currently working toward understanding the kinetic preference
for trans-2d as well the exact role of bismuth in these reactions.
The results of these further investigations will be reported in
due course.
Preparation of cis-Methyl-2-(6-benzyl-3,6-dihydro-2H-pyran-
2-yl)-2-methyl propanoate, 3: BiBr3 (44.9 mg, 0.010 mmol, 0.10
equiv) was weighed into a 25 mL round-bottom flask, and 10 mL
of CH2Cl2 was added via syringe. (Z)-4-(Trimethylsilyl)but-3-enal,
1d (0.142 g, 1.00 mmol, 1.00 equiv), and methyl trimethylsilyl
dimethylketene acetal (0.192 g, 1.10 mmol, 1.10 equiv) were added
by syringe simultaneously. The mixture was stirred, and TLC was
used to monitor the reaction until (Z)-4-(trimethylsilyl)but-3-enal,
1d, was consumed (3 h). Phenylacetaldehyde (0.240 g, 2.00 mmol,
2.00 equiv) and additional BiBr3 (44.9 mg, 0.010 mmol, 0.10 equiv)
were added, and the mixture was stirred for 12 h. The solution
was concentrated in vacuo, filtered through a small SiO2 pipet
column with CH2Cl2 as eluent, and concentrated in vacuo again.
The product was purified by column chromatography (9:1 petroleum
ether:ethyl ether, Rf ) 0.34) to provide 0.176 g (64%) of cis-isomer,
3, as a colorless oil: IR (neat) 3031(s), 2982(s), 2940(s), 2879(m),
1735(s), 1451(m), 1267(s), 1140(s), 1086(s), 751(m); 1H NMR (400
MHz, CDCl3) δ 7.17-7.28 (m, 5H), 5.77-5.82 (m, 1H), 5.63 (dm,
J ) 10.3 Hz, 1H), 4.27 (br, 1H), 3.77 (dd, J ) 11.0, 3.3 Hz, 1H),
3.55 (s, 3H), 2.83 (dd, J ) 13.9, 8.1 Hz, 1H), 2.70 (dd, J ) 13.9,
8.1 Hz, 1H), 2.06-2.15 (m, 1H), 1.77-1.85 (m, 1H), 1.20 (s, 3H),
1.11(s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.2(e), 138.7(e),
129.72(o), 129.70(o), 128.0(o), 126.1(o), 125.0(o), 78.4(o), 76.5-
(o), 52.0(o), 46.6(e), 42.1(e), 25.4(e), 21.3(o), 20.4(o). Anal. Calcd
for C17H22O3 (274.35): C, 74.42; H, 8.08. Found: C, 74.53; H,
8.30.
Experimental Section
General Procedure for the Synthesis of Dihydropyrans: BiBr3
(11.2 mg, 0.025 mmol, 0.050 equiv) was weighed into a 10 mL
round-bottom flask, and 5 mL of CH2Cl2 was added via syringe.
Aldehyde (1.00 mmol, 2.00 equiv) and vinylsilane (0.50 mmol,
1.00 equiv) were added by syringe sequentially. The mixture was
stirred for 12 h, concentrated in vacuo, filtered through a small
SiO2 pipet column with CH2Cl2 as eluent, and concentrated in vacuo
again. The product was then purified by flash column chromatog-
raphy on silica gel.
Preparation of cis-6-(4-Methoxyphenyl)-2-pentyl-3,6-dihydro-
2H-pyran, 2d. According to the general procedure, p-anisaldehyde
(0.136 g, 1.00 mmol, 2.00 equiv) was treated with (Z)-4-(triethyl-
silyloxy)-1-(trimethylsilyl)non-1-ene, 1b (0.164 g, 0.500 mmol, 1.00
equiv), to provide 0.076 g (58%) of cis-isomer as a colorless liquid,
after purification by column chromatography (9:1 pentane:ethyl
ether, Rf ) 0.54): IR (neat) 3036(m), 2932(s), 2861(s), 1614(m),
1513(s), 1458(m), 1247(s), 1177(m), 1072(s), 1040(s), 818(m)
Acknowledgment. We gratefully acknowledge the support
of the National Science Foundation (CAREER Award, 9983863).
R.J.H. also sincerely thanks the Camille and Henry Dreyfus
Foundation for a Henry Dreyfus Teacher-Scholar Award, the
Thomas F. and Kate Miller Jeffress Memorial Trust, and the
Petroleum Research Fund (PRF) of the American Chemical
Society.
1
cm-1; H NMR (400 MHz, CDCl3) δ 7.30 (d, J ) 8.4 Hz, 2H),
6.88 (d, J ) 8.8 Hz, 2H), 5.90-5.95 (m, 1H), 5.74 (m, 1H), 5.11
(27) Chair conformations in sigmatropic rearrangements are widely
accepted (see refs 9g and 22-24). We have not yet ruled out the possibility
of a boat topography as reported by Huang and Panek in an allylic system:
Huang, H.; Panek, J. S. J. Am. Chem. Soc. 2000, 122, 9836-9837.
(28) Hinkle, R. J.; Lian, Y. Unpublished results.
(29) Peidro, L.; Le Roux, C.; Laporterie, A.; Dubac, J. J. Organomet.
Chem. 1996, 521, 397-399.
Supporting Information Available: Detailed experimental
1
1
procedures, H and 13C APT NMR spectra, as well as H NOE
difference spectra for compounds 1a-d, 2a-j, and 3. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO060738K
7074 J. Org. Chem., Vol. 71, No. 18, 2006