A Lewis acid mediated stereoselective removal of an anomeric urea substituent

Article abstract of DOI:10.1055/s-2003-38747

The first Lewis acid mediated stereoselective removal of an anomeric chiral urea group or an electron deficient nitrogen substituent is described here. The ability to remove this urea group which had served as a chiral auxiliary, along with stereoselective hydroboration-oxidation of the endocyclic olefin renders the pyranyl cycloadduct from hetero [4+2] cycloadditions of chiral allenamides a useful chiral template. This represents a new approach to synthesis of complex pyranyl heterocycles or C-glycoside derivatives.

Full text of DOI:10.1055/s-2003-38747

LETTER
791
A Lewis Acid Mediated Stereoselective Removal of an Anomeric Urea
Substituent
A
Lewis
Acid
M
r
diated
S
a
tereoselect
i
ive Rem
g
oval of anAnome
R
ric
U
rea Substitu
.
ent Berry, C. Rameshkumar, Michael R. Tracey, Lin-Li Wei, Richard P. Hsung*1
Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA
E-mail: hsung@chem.umn.edu
Received 7 October 2002
Abstract: The first Lewis acid mediated stereoselective removal of
an anomeric chiral urea group or an electron deficient nitrogen sub-
stituent is described here. The ability to remove this urea group
which had served as a chiral auxiliary, along with stereoselective
hydroboration-oxidation of the endocyclic olefin renders the pyran-
yl cycloadduct from hetero [4+2] cycloadditions of chiral allen-
amides a useful chiral template. This represents a new approach to
synthesis of complex pyranyl heterocycles or C-glycoside deriva-
tives.
Key words: Lewis acid, [4+2] cycloaddition, C-glycoside deriva-
tives
Allenamides, an electron-deficient variant of allenamines
in which the nitrogen atom is substituted with an electron
withdrawing acyl group, have emerged as useful synthons
in organic synthesis.2–6 The vastly improved stability and
Scheme 1
comparable reactivity of allenamides relative to allena-
mines have rendered them attractive in developing new
stereoselective methodologies.3,4 A while back we report-
ed [4+2] cycloaddition reactions of the chiral allenamide
1 with hetero dienes such as vinyl ketones 2, leading to
pyranyl heterocycles 3 in a highly stereoselective manner
(Scheme 1).4a This represents the first account of an in-
verse electron-demand hetero [4+2] cycloaddition involv-
ing a chiral enamide.7,8 Mechanistically, it remains
unclear as to the source of such high diastereoselectivities
since the cycloaddition likely proceeds stepwise, although
a model has been proposed based on the structural planar-
ity of allenamides observed from modeling and crystal
structure.4a,5b,c,6b Synthetically, this highly stereoselective
cycloaddition led us to explore a new approach for con-
structing C-glycosides.9,10
directed by the urea carbonyl group. Therefore, the pyran
3, cycloadducts from hetero [4+2] cycloadditions of chiral
allenamides, represents a unique chiral template with the
imidazolidinone group at C6 being a chiral auxiliary for
constructing highly functionalized C-glycosides or pyran-
yl heterocycles that can lead to relevant natural products.
We report here our success in achieving a key Lewis acid
mediated stereoselective removal of the chiral imidazoli-
dinone at C6.
To render the pyran 3 a unique chiral template, two impor-
tant concepts must be realized: 1) Stereoselective func-
tionalization of the two olefins in 3 leading to 4, and 2) a
key removal of the chiral imidazolidinone at C6 in 4 that
served as an auxiliary (Scheme 2). However, there is very
few literature precedents describing useful removal of an
electron deficient nitrogen substituent or an anomeric urea
group.11 Therefore, this second concept is a non-trivial
task and became our primary focus. Our proposed ap-
proach for such a removal is shown in Scheme 2. A suit-
able Lewis acid could facilitate the departure of the C6
urea group in 4 via coordination to the carbonyl group to
give an oxocarbenium ion 5. An addition of a suitable nu-
cleophile to 5 could lead to the pyran 6 stereoselectively.
The X-ray analysis and AM-1 minimization [SpartanTM
]
of the pyran 3 reveal that the chiral imidazolidinone group
at C6 is oriented pseudo-axially, situating beneath the two
easily distinguishable olefins with one being electron-rich
and endocyclic at C2/C3, and the other being exocyclic at
C5 (Scheme 1). Such shielding of the bottom face sup-
ports the high stereoselectivity observed when these two
olefins were hydrogenated sequentially.4a Based on this
analysis, we envisioned that stereoselective transforma-
tion of these two well-differentiated olefins can occur ei-
ther on the sterically less congested top face, or may be
To achieve this proposed sequence, a series of Lewis acids
were screened carefully at various equivalents and differ-
ent temperatures. These results are summarized in
Table 1. Reactions were carried out using the pyran 812 as
a simplified model readily attainable from hydrogenation
of 7, and allyltrimethylsilane9,13 was used as the nucleo-
Synlett 2003, No. 6, Print: 05 05 2003.
Art Id.1437-2096,E;2003,0,06,0791,0796,ftx,en;S05602ST.pdf.
© Georg Thieme Verlag Stuttgart · New York

792
C. R. Berry et al.
LETTER
phile. The most effective Lewis acid turned out to be
SnBr4,14,15 and in the presence of 4.0 equivalents of allyl-
trimethylsilane, the allylation product 916 was isolated in
49–77% yield with 60–66% de (entries 14 and 15). The
amount of SnBr4 appeared to be quite critical with the op-
timum being 1.0–1.5 equivalents (comparing entries 9–
16). Although BF3·OEt2 provided higher de (entries1–3),
yields were inferior owing to hydrolysis or ring-opening
of the pyran 8.
Isolation of the chiral imidazolidinone (the Close auxilia-
ry)17 suggests that the loss of the imidazolidinone had
been facilitated via the usage of SnBr4 where the oxocar-
benium ion 10 was likely the intermediate (Scheme 3).
The stereochemical assignment of the major isomer 9a
based on NOE implies that the allyltrimethylsilane had
added in an anomerically favored axial trajectory to the
oxocarbenium intermediate 10 where the bulky aromatic
group at C2 predominates and assumes an equatorial
position.9,12–15,18
Scheme 2
Table 1 Reaction Results with a Series of Lewis Acids at Various Equivalents and Different Temperatures
Entry
1
Lewis acid (equiv)
BF3⋅OEt2 (2.5)
BF3⋅OEt2 (2.0)
BF3⋅OEt2 (1.5)
TiCl4 (1.2)
Silane (equiv)
Temp
Time (h)
Yielda
40%
33
Ratio (9a:9b)b
83:17
84:16
90:10
NDc
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
5.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
–78 °C to r.t.
–78 °C to r.t.
–78 °C to r.t.
–78 °C to r.t.
–78 °C to r.t.
–78 °C to r.t.
–78 °C to r.t.
r.t.
24
5
2
3
2
10
4
1
decomp.
decomp.
decomp.
60
5
TMSOTf (2.4)
ZnCl2 (1.2)
InCl3 (1.5)
1
ND
6
18
48
72
5
ND
7
67:33
51:49
75:25
53:47
67:33
75:25
ND
8
InCl3 (1.5)
10
9
SnBr4 (5.0)
SnBr4 (3.0)
SnBr4 (2.5)
SnBr4 (2.0)
SnBr4 (1.5)
SnBr4 (1.5)
SnBr4 (1.0)
SnBr4 (0.5)
0 °C to r.t.
–78 °C to r.t.
–78 °C to r.t.
–78 °C to r.t.
–78 °C
30
10
11
12
13
14
15
16
18
18
18
3
65
67
67
20
–78 °C to r.t.
–40 °C
12
48
60
77
80:20
83:17
67:33
49
–78 °C
60
a Isolated yields.
b Ratios determined by 1H NMR.
c ND: Not determined.
Synlett 2003, No. 6, 791–796 ISSN 1234-567-89 © Thieme Stuttgart · New York

LETTER
A Lewis Acid Mediated Stereoselective Removal of an Anomeric Urea Substituent
793
lowed by addition of a hydride to the epoxy intermediate
17 (Scheme 5). The potential obstacle was that unlike 1,2-
anhydro sugars (or glycosidic epoxides),9 there are very
few examples of stable epoxy intermediates such as 17,19
and isolated ones are extremely acid sensitive.20 Most ep-
oxides of this type would undergo rapid ring-opening to
give an oxocarbenium intermediate that would lead to
eventual scrambling of stereochemistry at the anomeric
center.9,20
Scheme 3
Based on this proposed conformation for 10, the C5 pseu-
do axial methyl group could further disfavor the nucleo-
phile to approach 10 from an equatorial trajectory.
However, the addition of more bulky allyltri-iso-propyl-
or allyltriphenylsilane did not improve the overall diaste-
reoselectivity. Although the diastereoselectivity observed
here is only modest for a simplified system, this is the first
example of removal of an anomeric urea group.
Scheme 5 a) 2.0 Equiv MCPBA, CH2Cl2, phosphate buffer, –10 °C
to r.t., 18 h. Ratio of 18a:18b: 84:16 (60%); ratio of 19a:19b: 80:20
(75%). b) 2.0 Equiv magnesium monoperoxyphthalate (MMPP),
THF, H2O, –10 °C to r.t., 17 h. Only 19b (70%) as a single isomer.
As shown in Scheme 5, epoxidations of 14 and 16 using
m-CPBA led to diols 18a and 18b (ratio 84:16), and 19a
and 19b ([ratio 80:20), in 60% and 75% yield, respective-
ly. This outcome implies that addition of hydride to C2
may not compete well with H2O. NOE experiments unam-
biguously confirmed that MCPBA had actually added se-
lectively from the more congested bottom face leading to
a C3-a-OH in 18 and 19. Although the stereochemistry at
C2 could not be unambiguously assigned, stereochemistry
of 18b (or 19b)] was also confirmed to be epimeric at C6
relative to 18a (or 19a)]. The diol 18a (or 19a) appeared
to be prone to epimerization at C6 leading to 18b (or 19b).
When the diol 18a or 19a was subjected to acylating or si-
lylating conditions, 18b or 19b was isolated quantitative-
ly, and MMPP epoxidation of 16 also led to only the
epimer 19b. While these results warrant further studies
because it implies a potential urea-directed epoxidation,
we shifted our attention because a successful hydrobora-
tion could be carried out using BH3·SMe2 to achieve the
equivalent task.
Scheme 4
Having established the feasibility of SnBr4-mediated re-
moval of the chiral imidazolidinone at C6, its scope can be
shown using pyrans with other aromatic substituents at C2
(see 11 and 14 in Scheme 4, and more examples are in the
supplementary material). Other allyltrialkylsilanes could
also be used to provide products such as 13. Comparing
with the diastereoselectivity observed for 9, these exam-
ples provided lower diastereoselectivities suggesting that
the substituent at C2 is likely more significant to the ste-
reochemical outcome than the size of allyltrialkylsilanes.
Particularly, by flattening out at C2/C3 as shown in 14,
any sense of diastereoselectivity was completely lost dur-
ing the allylation presumably due to a more planar oxocar-
benium intermediate.
As shown in Scheme 6, a sequence of hydroboration–ox-
idation using 16 consisting of 2.0 equivalents BH3⋅SMe2
and 30% aqueous H2O2 with 15% aqueous NaOH led to
the alcohol 20 as a single diastereomer. The relative
stereochemistry was assigned using NOE experiments,
and no epimerization occurred at C6 during the hydro-
boration-oxidation. A subsequent allylation, without pro-
tecting the hydroxyl group, under the standard conditions
of using 1.5 equivalents SnBr4 led to the pyran 21 in 70%
yield with an improved 72–76% de.
With this methodology in place, we began exploring ste-
reoselective transformation involving the two olefins in
the pyran 7. The initial investigation was focusing on ep-
oxidation of the endocyclic olefin at C2/C3 in 14 or 16 fol-
Synlett 2003, No. 6, 791–796 ISSN 1234-567-89 © Thieme Stuttgart · New York

794
C. R. Berry et al.
LETTER
We have described here the first Lewis acid mediated
stereoselective removal of an anomeric urea group (or an
electron deficient nitrogen substituent). This methodolo-
gy along with stereoselective hydroboration–oxidation of
the endocyclic olefin renders pyranyl cycloadducts from
hetero [4+2] cycloadditions of chiral allenamides with a
useful chiral template leading to a new approach to con-
structing pyranyl heterocycles or C-glycosides.
Acknowledgment
Funding from NSF [CHE-0094005], J&J PRI, and the McKnight
Foundation are greatly appreciated. We thank Drs. Victor Young
and Neil R. Brooks, and Mr. William W. Brennessel for solving
the X-ray structure. We thank Professors Keith Woerpel and Dan
Comins for valuable discussions.
References
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(c) For documentations of earlier allenamides, see:
Scheme 6
The relative stereochemistry was assigned using NOE21
(Scheme 6) with the allyl group again adding in an axial
trajectory. The improved de suggests that additional sub-
stitutions on the pyranyl ring could lead to a conforma-
tionally more rigid oxocarbenium intermediate14,18
leading to higher diastereoselectivity, although we are not
certain if the C3 hydroxyl group played any role in direct-
ing the incoming silane.
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Another interesting observation was that the pyran 20 did
epimerize completely at C6 leading to 22 cleanly (see
NOE arrows21) when attempts were made to silylate the
C3 hydroxyl group. Allylation of 22 led to 21 in a compa-
rable 75% yield but with a noticeable and consistently
higher de in 78–80%. This observation led to the specula-
tion that allylations of 20 and 22 could proceed through
slightly different transition states with the latter having
more of an oxocarbenium ion character.9 This also sug-
gests that the rate of departure of the urea group could de-
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(c) Kozawa, Y.; Mori, M. Tetrahedron Lett. 2001, 42, 4869.
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Finally, this protocol could be extended to other systems
leading to successful preparations of pyrans or C-glyco-
side type derivatives such as 23 and 24 with an overall
yield of 4.0% and 3.1%, respectively (unoptimized). The
diastereoselectivity was found to be in the hydroboration–
oxidation step (>15:1 in the case of 23 and 12:1 in the case
of 23) as well as the allylation step (2:1 for 23 and 2–3:1
for 24). These relatively short sequences for the synthesis
of 23 and 24 are also attractive because they are devoid of
protection and deprotection steps during the functionali-
zation of the pyran ring.
Synlett 2003, No. 6, 791–796 ISSN 1234-567-89 © Thieme Stuttgart · New York

LETTER
A Lewis Acid Mediated Stereoselective Removal of an Anomeric Urea Substituent
795
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Figure 1
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(16) For selected experimental procedures and characterizations:
General Procedure for Lewis Acid Mediated Allylations
Using Pyran 8: To a solution of 317.7 mg of pyran 8 in 65
mL of freshly distilled CH2Cl2 at –78 °C under N2 were
added 503.9 mg of SnBr4 (1.5 equiv, 1.16 mmol) and 0.488
mL of allyltrimethylsilane (4 equiv, 3.06 mmol). The
reaction was vigorously stirred for 12 h and allowed to
slowly warm to r.t. The solvent was removed under reduced
pressure and purification using silica gel column
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some examples where removal of an electron deficient
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8169.
chromatography afforded 157.6 mg of 9a and 9b as a
mixture in addition to recovery of the Close’s auxiliary in
70–90% recovery range when attempted. The ratio of 9a:9b
was found to be 4:1 from the crude 1H NMR. Preparative
thin layer chromatography (1% Et2O in hexanes) was useful
to separate the major isomer 9a from the minor isomer 9b.
9a (major). Rf = 0.30 (10% Et2O in hexanes). 1H NMR (500
MHz, CDCl3): d = 1.06 (d, J = 7.0 Hz, 3 H), 1.70 (m, 1 H),
1.78 (m, 1 H), 2.03 (m, 2 H), 2.18 (m, 1 H), 2.47 (ddd,
J = 1.0, 10.0, 18.0 Hz, 2 H) 3.43 (ddd, J = 6.0, 7.0, 7.0 Hz, 1
H), 4.96 (dd, J = 1.0, 10.0 Hz, 1 H), 5.04 (dd, J = 2.0, 15.0
Hz, 1 H), 5.52 (dd, J = 4.0, 8.0 Hz, 1 H), 5.74 (m, 1 H), 7.27–
8.31 (m, 7 H). 13C NMR (125 MHz, C6D5CD3): d = 137.9,
135.8, 134.2, 128.8, 128.5, 127.8, 125.4, 125.2, 125.1,
124.8, 124.2, 115.6, 76.8, 69.6, 36.8, 32.2, 27.4, 27.3, 17.8.
IR (thin film): 3052 (m), 2932 (m), 1641 (m) cm–1. MS (EI):
m/e (% relative intensity) = 266.2 (25) [M+], 249.6 (100).
Optical rotation was not pursued because samples of 9a still
contained some 9b.
9b (minor). Rf = 0.30 (10% Et2O in hexanes). 1H NMR (500
MHz, CDCl3): d = 1.06 (d, J = 7.0 Hz, 3 H), 1.55 (m, 3 H),
1.74 (m, 1 H), 2.03 (m, 2 H), 2.65 (m, 1 H), 4.01 (dd, J = 4.0,
10.0 Hz, 1 H), 4.97 (d, J = 10.0 Hz, 1 H), 5.11 (d, J = 17.0
Hz, 1 H), 5.33 (dd, J = 1.0, 10.0 Hz, 1 H), 5.88 (m, 1 H),
7.07–8.25 (m, 7 H). 13C NMR (125 MHz, C6D5CD3): d =
136.0, 128.9, 128.8, 127.8, 127.5, 125.4, 123.8, 123.6,
115.7, 76.8, 68.1, 33.3, 32.6, 30.5, 27.6, 16.7 (3 signals are
missing overlap with solvent). IR (thin film): 3064 (m), 2945
(m), 1635 (m)cm–1. MS (EI): m/e (% relative intensity) =
284.2(50) [M + NH4]+, 264.1(10), 247.1(100); m/e
calculated for C19H26NO: 284.2015. Found: 284.2015.
General Procedure for Lewis Acid Mediated Allylations
Using Pyran 20: To a solution of pyran 20 (5.0 mg, 0.011
(12) The X-ray structure of pyran 8 is available in supplementary
materials (Figure 1).
Synlett 2003, No. 6, 791–796 ISSN 1234-567-89 © Thieme Stuttgart · New York

796
C. R. Berry et al.
LETTER
mmol) in 1.0 mL of anhyd CH2Cl2 at –78 °C were added
7.63 mg SnBr4 (1.5 equiv, 0.0174 mmol) and 7.50 mL of
allyltrimethylsilane (4 equiv. 0.0464 mmol). The mixture
was warmed to r.t. and stirred at r.t. for 12 h before it was
quenched with sat. aq NH4Cl (2 mL). The resultant mixture
was extracted with CH2Cl2 (3 × 3 mL), and the combined
extracts were dried over Na2SO4, filtered, and concentrated
under reduced pressure. Silica gel flash chromatography
(gradient eluent: 0–10% EtOAc in hexanes) of the crude
gave 2.32 mg (combined yield 70%) of pyran 21a and 22b
with a 7:1 diastereomeric ratio.
provided 6.62 mg of the desired alcohol 20 (70% yield) as a
colorless oil.
20
Pyran 20: Rf = 0.35 (50% EtOAc in hexanes). [a]D
=
–77.0 (c 0.35, CHCl3). 1H NMR (500 MHz, CDCl3): d = 0.68
(d, J = 7.0 Hz, 3 H), 0.94 (d, J = 6.5 Hz, 3 H), 2.01 (ddd,
J = 3.5, 7.0, 10.0 Hz, 2 H), 2.25 (m, 1 H), 2.67 (s, 3 H), 3.72
(dq, J = 7.0, 8.5 Hz, 1 H), 4.02 (dd, J = 7.5, 16.0 Hz, 1 H),
4.84 (d, J = 8.0 Hz, 1 H), 5.04 (d, J = 9.0 Hz, 1 H), 5.63 (d,
J = 2.0 Hz, 1 H), 7.20–8.41 (m, 12 H). 13C NMR (125 MHz,
CDCl3): d = 162.5, 139.0, 134.9, 133.8, 131.7, 128.8, 128.5,
128.2, 127.5, 126.1, 125.7, 125.3, 125.0, 124.4, 86.3, 82.4,
67.3, 58.9, 57.1, 40.2, 32.6, 28.6, 15.1, 13.9 (missing 3
signals). IR (thin film): 3391 (m), 3029 (w), 2980 (w), 2930
(m), 2878 (m), 1684 (s), 1435 (m) cm–1. MS (EI): m/e (%
relative intensity) = 430.3(5) [M+], 273.2(100); m/e calcd for
C27H30N2O3: 430.2256. Ffound: 430.2234.
Pyran 21a (major): Rf = 0.30 (10% EtOAc in hexanes). 1H
NMR (500 MHz, CDCl3): d = 0.99 (d, J = 7.0 Hz, 3 H), 1.36
(ddd, J = 6.0, 12.0, 18.0 Hz, 1 H), 1.75 (dd, J = 12.0, 22.0
Hz, 1 H), 1.86 (m, 1 H), 2.27 (ddd, J = 6.5, 14.0, 15.0 Hz, 1
H), 2.42 (ddd, J = 4.5, 11.0, 16.5 Hz, 1 H), 2.71 (d, J = 1.5
Hz, 1 H), 3.68 (ddd, J = 4.5, 7.0, 15.5 Hz, 1 H), 4.46 (ddd,
J = 3.5, 8.5, 15.5 Hz, 1 H), 5.13 (ddd, J = 9.5, 15.5, 17.5 Hz,
2 H), 5.84 (d, J = 2.0 Hz, 1 H), 5.94 (m, 1 H), 7.08–8.20 (m,
7 H). 13C NMR (75 MHz, CDCl3): d = 134.9, 128.7, 127.5,
125.8, 125.4, 125.2, 122.8, 122.6, 116.7, 86.0, 80.6, 69.7,
39.0, 38.5, 33.5, 16.2 (missing 3 peaks). IR (thin film): 3432
(s), 3072 (w), 3063 (w), 2971 (s), 2962 (s), 2953 (s) cm–1.
MS (EI): m/e (% relative intensity) = 282.2 (15) [M+],
125.1(100); m/e calcd for C19H22O2: 282.1620. Found:
282.1618.
Pyran 22 [C6-epimer]: Rf = 0.35 (50% EtOAc in hexanes).
1H NMR (500 MHz, CDCl3): d = 0.80 (d, J = 7.0 Hz, 3 H),
1.03 (d, J = 6.0 Hz, 3 H), 1.15 (ddd, J = 3.0, 5.0, 12.0 Hz, 1
H), 1.67 (dd, J = 12.0, 23.0 Hz, 1 H), 2.46 (m, 1 H), 2.81 (s,
3 H), 3.51 (ddd, J = 3.5, 5.0, 10.5 Hz, 1 H), 3.79 (dq, J = 6.5,
8.5 Hz, 1 H), 4.69 (d, J = 8.5 Hz, 1 H), 5.37 (d, J = 9.0 Hz, 1
H), 5.45 (d, J = 3.0 Hz, 1 H), 7.20–8.25 (m, 12 H). 13C NMR
(75 MHz, CDCl3): d = 167.6, 136.9, 134.9, 133.2, 128.6,
128.5, 128.3, 127.9, 127.8, 127.4, 125.6, 125.3, 125.1,
122.8, 90.9, 80.1, 68.4, 60.7, 55.7, 35.0, 32.2, 29.6, 28.5,
16.0, 14.5 (missing 2 peaks). MS (EI): m/e (% relative
intensity) = 430.3 (5) [M+], 273.2 (100); m/e calcd for
C27H30N2O3: 430.2256. Found: 430.2232.
Pyran 21b (minor): Rf = 0.32 (10% EtOAc in hexanes). 1H
NMR (500 MHz, CDCl3): d = 0.98 (d, J = 7.0 Hz, 3 H), 1.33
(ddd, J = 11.0, 20.5, 22.5 Hz, 1 H), 1.64 (dd, J = 5.5, 15.5
Hz, 1 H), 2.28 (m, 3 H), 2.82 (s, 1 H), 4.05 (ddd, J = 10.0,
13.0, 22.5 Hz, 1 H), 4.36 (ddd, J = 5.5, 10.5, 16.0 Hz, 1 H),
5.22 (m, 2 H), 5.82 (d, J = 4.5 Hz, 1 H), 5.98 (m, 1 H), 7.30–
8.20 (m, 7 H). MS (EI): m/e (% relative intensity) =
282.2(15) [M+], 125.1(100); m/e calcd for C19H22O2:
282.1620. Found: 282.1617.
Hydroboration Reactions: To a solution of 9.0 mg of pyran
16 (0.0218 mmol) in 2.0 mL of anhyd THF at r.t. was added
0.25 mL of BH3·THF complex (2.5 equiv, 1 M solution in
THF). The resultant mixture was stirred for 1 h and warmed
to 55 °C for 1 h, and then, the mixture was cooled to r.t. and
excess 30% aq H2O2 and 15% aq NaOH was added dropwise
carefully. The resultant mixture was warmed to 60 °C for 10
min and vigorously stirred at r.t. for 1 h. The mixture was
extracted with Et2O (2 × 5 mL) and EtOAc (2 × 5 mL). The
combined extracts were dried over Na2SO4, filtered, and
concentrated under reduced pressure. Silica gel flash
chromatography (50% EtOAc in hexanes) of the crude
(17) Close, W. J. J. Org. Chem. 1950, 15, 1131.
(18) (a) Woods, R. J.; Andrews, C. W.; Bowen, J. P. J. Am. Chem.
Soc. 1992, 114, 859. (b) Miljkovic, M.; Yeagley, D.;
Deslongchamps, P.; Dory, Y. L. J. Org. Chem. 1997, 62,
7597.
(19) Bezuidenhoudt, B. C. B.; Barend, C. B.; Castle, G. H.; Innes,
J. E.; Ley, S. V. Recl. Trav. Chim. Pays-Bas 1995, 114, 184.
(20) (a) Fujiwara, K.; Awakura, D.; Tsunashima, M.; Nakamura,
A.; Honma, T.; Murai, A. J. Org. Chem. 1999, 64, 2616.
(b) Evans, D. A.; Carter, P. H.; Carreira, E. M.; Charette, A.
B.; Prunet, J. A.; Lautens, M. J. Am. Chem. Soc. 1999, 121,
7540.
(21) When substituents at C5 and C6 are trans in these pyranyl
heterocycles, we observed strong NOE (see pyrans 21 and
22) between protons at C2 and C3 presumably because these
two protons are not necessarily locked in a diaxial
relationship unlike those in 20.
Synlett 2003, No. 6, 791–796 ISSN 1234-567-89 © Thieme Stuttgart · New York