Chelation-assisted regioselective C-O bond cleavage reactions of acetals by Grignard reagents. A general procedure for the regioselective synthesis of protected polyols having one free hydroxy group

Article abstract of DOI:10.1021/jo981579a

Acetals containing a neighboring heteroatom react with the Grignard reagent in aromatic hydrocarbon solvents regioselectively. The auxiliary moiety can be hydroxy, alkoxy, or amino but not sulfur. Chelation plays a key role in directing the regioselectivity of this ring opening reaction. The reactions of acetonide derivatives of monosaccharides under these conditions afford the corresponding products having only one free hydroxy group at the specific position. Fully protected mannosamine derivative is prepared in good yield. The stereochemistry of the carbon center where auxiliary group is attached can be either syn or anti to the acetal oxygen moiety where cleavage of the C-O bond occurs. However, difference in reactivity has been found in the reaction of tris-acetonide of sorbitol with MeMgI. Regioselective ring opening of the acetal group at the anomeric carbon generates a hemiacetal which underwent further nucleophilic addition to furnish the corresponding alcohol stereoselectively.

Full text of DOI:10.1021/jo981579a

5
32
J . Org. Chem. 1999, 64, 532-539
Ch ela tion -Assisted Regioselective C-O Bon d Clea va ge Rea ction s
of Aceta ls by Gr ign a r d Rea gen ts. A Gen er a l P r oced u r e for th e
Regioselective Syn th esis of P r otected P olyols Ha vin g On e F r ee
Hyd r oxy Gr ou p
Wen-Lung Cheng, Yeng-J eng Shaw, Sue-Min Yeh, Puthuparampil P. Kanakamma,
Yu-Huey Chen, Chuo Chen, J ia-Cheng Shieu, Shaang-J yh Yiin, Gene-Hsiang Lee,
Yu Wang, and Tien-Yau Luh*
Department of Chemistry, National Taiwan University, Taipei, Taiwan 106
Received August 4, 1998
Acetals containing a neighboring heteroatom react with the Grignard reagent in aromatic
hydrocarbon solvents regioselectively. The auxiliary moiety can be hydroxy, alkoxy, or amino but
not sulfur. Chelation plays a key role in directing the regioselectivity of this ring opening reaction.
The reactions of acetonide derivatives of monosaccharides under these conditions afford the
corresponding products having only one free hydroxy group at the specific position. Fully protected
mannosamine derivative is prepared in good yield. The stereochemistry of the carbon center where
auxiliary group is attached can be either syn or anti to the acetal oxygen moiety where cleavage of
the C-O bond occurs. However, difference in reactivity has been found in the reaction of tris-
acetonide of sorbitol with MeMgI. Regioselective ring opening of the acetal group at the anomeric
carbon generates a hemiacetal which underwent further nucleophilic addition to furnish the
corresponding alcohol stereoselectively.
3
Differentiation of a contiguous polyol by the regiose-
chiral acetals. Lewis acids are occasionally used to assist
such reactions. Reductive cleavage of benzylidene acetals
or the like has been used for the regioselective synthesis
lective protection leading to the product having only one
or two free hydroxy group(s) at the selected position(s)
1
8
is valuable in synthesis. Acetal and ortho ester func-
of certain monosaccharide derivatives. Trimethylalumi-
tionalities are widely used protective groups for such
polyols. Direct transformation of a polyol into the corre-
sponding acetal or ortho ester leaving certain hydroxy
groups intact would be the ideal situation but successful
num has been employed to facilitate the alkylative ring
opening reaction. However, a mixture of regioisomers
5
is occasionally obtained. Although reactions of the Grig-
nard reagent with acetals have been known for more than
2
5
only in limited cases. Multistep protection and depro-
three decades and the mechanism for this transforma-
6
tection are occasionally required. Selective conversion of
an acetal moiety with a nucleophile into a hydroxyalkyl
ether serves as a practical arsenal for this purpose.3
The reaction has been demonstrated to be particularly
important for the diastereoselective ring opening of cyclic
tion has been extensively investigated, not much syn-
thetic use has been reported.5 We recently uncovered a
,7
-11
2
convenient synthesis of tunable C -chiral diols 3 by the
regioselective ring opening of bisketals of threitol 1 with
9
a variety of Grignard reagents in benzene (eq 1).
(
1) Greene, T. A.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 2nd ed.; Wiley: New York, 1991. (b) Kocienski, P. J .
Protective Groups; Thieme: New York, 1994.
(2) For a recent review, see: Hanessian, S., Ed.; Preparative
Carbohydrate Chemistry; Marcel Dekker: New York, 1997. See also:
Lee, H. W.; Kish, Y. J . Org. Chem. 1985, 50, 4402.
(3) (a) Bartlett, P. A.; J ohnson, W. S.; Elliott, J . D. J . Am. Chem.
Soc. 1983, 105, 2088. (b) Mori, A.; Fujiwara, J .; Maruoka, K.; Yama-
moto, H. Tetrahedron Lett. 1983, 24, 4581.
(4) (a) Takano, S.; Kurotaki, A.; Sekiguchi, Y.; Satoh, S.; Hirama,
M.; Ogasawara, K. Synthesis 1986, 811. (b) Takano, S.; Akiyama, M.;
Ogasawara, K. Chem. Pharm. Bull. 1984, 32, 791. (c) Takano, S.;
Akiyama, M.; Sato, S.; Ogasawara, K. Chem. Lett. 1983, 1593. (d)
Takano, S.; Ohkawa, T.; Ogasawara, K. Tetrahedron Lett. 1988, 29,
1
1
823. (e) Gilbert, I. H.; Holmes, A. B.; Young, R. C. Tetrahedron Lett.
990, 31, 2633. (f) Gilbert, I. H.; Holmes, A. B.; Pestchanker, N. J .;
Young, R. C. Carbohydr. Res. 1992, 234, 117.
5) (a) Mori, I.; Ishihara, L. A.; Flippin, L. A.; Nozaki, K.; Yamamoto,
H.; Bartlett, P. A.; Heathcock, C. H. J . Org. Chem. 1990, 55, 6107. (b)
Denmark, S. E.; Almstead, N. G. J . Am. Chem. Soc. 1991, 113, 8089;
J . Org. Chem. 1991, 56, 6458, 6485. (c) Sammakia, T.; Smith, R. S. J .
Org. Chem. 1992, 57, 2997; J . Am. Chem. Soc. 1992, 114, 10998.
(
Applications of this strategy to the synthesis of myo-
inositol derivatives having one or two free hydroxy group-
(8) Garegg, P. J . Pure Appl. Chem., 1984, 56, 845. Garegg, P. J . Acc.
Chem. Res. 1992, 25, 575. For chelative reductive cleavage of acetals,
see: Evans, D. A.; Kaldor, S. W.; J ones, T. K.; Clardy, J .; Stout, T. J .
J . Am. Chem. Soc. 1990, 112, 7001. Takano, S.; Kurotaki, A.; Sekiguchi,
Y.; Satoh, S.; Hirama, M.; Ogazawara, K. Synthesis 1986, 811.
(9) Yuan, T.-M.; Hsieh, Y.-T.; Yeh, S.-M.; Shyue, J .-J .; Luh, T.-Y.
Synlett 1996, 53.
(6) (a) Blomberg, C.; Vreugdenhil, A. D.; Homsma, T. Recl. Trav.
Chim. 1963, 82, 355. (b) Mallory, R. A.; Rovinski, S.; Scheer, I. Proc.
Chem. Soc. London 1964, 416.
(7) For reviews, see: (a) Trofimov, B. A.; Korostova, S. E. Russ.
Chem. Rev. 1975, 44, 41. (b) Mukaiyama, T.; Murakami, M. Synthesis
1
1
987, 1043. (c) Alexakis A.; Mangeney, P. Tetrahedron: Asymmetry
990, 1, 477. (d) Luh, T.-Y. Pure Appl. Chem. 1996, 68, 635. (e) Luh,
(10) Yeh, S.-M.; Lee, G.-H.; Wang, Y.; Luh, T.-Y. J . Org. Chem. 1997,
62, 8315.
T.-Y. Synlett 1996, 201.
1
0.1021/jo981579a CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/31/1998

Chelation-Assisted Regioselective C-O Cleavage
s) have been executed (eq 2).10 The Grignard reagent can
J . Org. Chem., Vol. 64, No. 2, 1999 533
(
vary among primary, secondary, and arylmagnesium
halides. It is believed that chelation has played a key role
in directing the regioselectivity of this ring opening
reaction. Accordingly, a possible chelation intermediate
the regioselectivity of the ring opening reaction. The
stereochemistry in 9 was unambiguously proved by X-ray
diffraction (Figure 1, Supporting Information).
When bis-acetonide 10 was treated with MeMgI in
benzene at 60 °C, mono-hydroxy compound 11 was
obtained in 48% yield (eq 6). Mannitol derivative 12 was
2
has been postulated to rationalize the selectivity of this
reaction. We felt that this reaction could be extended to
the selective protection/deprotection of various polyhy-
droxy-compounds having only one or two free hydroxyl
group. Described herein is a full account which demon-
strates a useful regioselective ring-opening reaction of
acetals with Grignard reagents.11
transformed into the corresponding mono-hydroxy prod-
uct 13 in refluxing benzene (eq 7). When more drastic
conditions were employed, diol 14 was isolated in good
yield (eq 7). When an unsymmetrical bis-acetonide 15
Resu lts a n d Discu ssion
P r ototyp e. On the basis of the chelation strategy
depicted above (eq 1), acetonides can be cleaved regiose-
lectively with Grignard reagents when a neighboring het-
eroatom is present.11 Accordingly, selective cleavage of
one of the two C-O bonds in the acetal-protected mono-
saccharides will offer a powerful arsenal for the selective
synthesis of various monosaccharide derivatives having
only one free hydroxy group at the specific position.
In the beginning of this investigation, we compared the
selectivity of the ring opening reactions of unchelated
acetonides to those of chelated ones. Thus, acetals 4 were
treated with 4 equiv of MeMgI in refluxing benzene-ether
(5:1) for 20 h. After the usual workup procedure, the
corresponding hydroxyalkyl ethers 5 were obtained in
4
good yields (eq 3). Both five- and six-membered aceto-
was employed, the less hindered heterocycle underwent
alkylative ring opening (eq 8). This protocol serves as a
powerful arsenal for the synthesis of various carbohy-
drate derivatives having selectively one free hydroxy
group at the specific position.
nides behaved similarly and the C-O bond of the less-
hindered site in 4 was cleaved regioselectively. Presum-
ably, the oxygen atom on this site would coordinate to
magnesium preferentially, resulting in the regioselective
protection of the more-hindered hydroxy group of the diol.
The presence of a neighboring oxygen or nitrogen
moiety changed the selectivity of the ring-opening reac-
tion. For example, the reaction of 6 with MeMgI afforded
the corresponding diol 7 in 78% yield (eq 4). The
neighboring amino group behaved similarly (eq 5). As
Ster eoch em istr y of th e Au xilia r y. As can be seen
from eqs 4-7, the stereochemistry of the carbon center
where auxiliary group is attached can be either syn or
anti to the acetal oxygen moiety where cleavage of the
C-O bond occurs. In a similar manner, stereoisomers 17
(
11) For preliminary communications, see: Cheng, W.-L.; Yeh, S.-
depicted in eq 1, the hydroxy group in 6 or the amino
group in 8 apparently plays a pivotal role in determining
M.; Luh, T.-Y. J . Org. Chem. 1993, 58, 5576. Chen, Y.-H.; Luh, T.-Y.;
Lee, G.-H.; Peng, S.-M. J . Chem. Soc., Chem. Commun. 1994, 2369.

5
34 J . Org. Chem., Vol. 64, No. 2, 1999
Cheng et al.
and 19 were transformed into respective diols 18 and 20
smoothly upon treatment with MeMgI (eqs 9 and 10).
might be expected to be less than that in 25. Accordingly,
chelation intermediate 26 may be formed preferentially
and determine the selectivity.
Mon osa cch a r id e Der iva tives Ha vin g On e F r ee
Hyd r oxy Gr ou p . In our preliminary communication, we
disclosed the usefulness of the chelation-controlled selec-
tive alkylative ring-opening of acetonides of methyl
glucosides 27 (eq 12).11 The reaction provides a useful
entry toward a glucoside derivative 28 having a free
2
hydroxy group at C . The chelation of the anomeric
However, difference in the reactivity has been found
methoxy group and the neighboring oxygen function at
in the reaction of tris-acetonide of sorbitol 21 with MeMgI
2
C in 27 with magnesium may explain the results. It is
(
eq 11). The structure of product 22 was determined by
X-ray crystallography of the corresponding benzyl ether
3 (Figure 2, Supporting Information). 5-Hydroxy deriva-
noteworthy that the anomeric methoxy group can be
either R or â. Furthermore, the trans-fused five-mem-
bered acetonide moiety in 27 apparently is more reactive
because the steric strain will be released upon alkylative
ring-opening reaction.
2
tive 24 was not detected.
The extension of this reaction to allyl glucoside 29 also
afforded the corresponding mono-hydroxy derivative 30.
Further transformations13 led to a convenient synthesis
of fully protected mannosamine 31 (eq 13).
The regioselectivity of the reaction of 21 can be
rationalized by considering the relative stability of the
chelation intermediates 25 and 26.12 In 25, the magne-
sium chelates with the oxygen atoms at C
4 5
and C which
will lead to the formation of 24. The relative configuration
Upon treatment with with MeMgI, glucosides 32 and
3
4 afforded 33 and 35 in 58% and 55% yield, respectively.
4 5
at C and C can be considered as meso form of a threitol
derivative. As can be seen from 25, severe steric interac-
tion might be expected between the two endo-methyl
groups and the endo-ligand on magnesium. Intermediate
2
6 on alkylative ring opening will furnish 22. Since only
The presence of a â-methoxy group at C
be irrelevant for the selectivity of this ring-opening
process because the reaction of allose derivative 36, a C
epimer of 34, also afforded 54% yield of the corresponding
3
in 34 seems to
3
one of the endo-methyl groups will interact with one of
the ligands on magnesium in 26, the steric repulsion
5
-OH product 37. These results suggested that chelation
(
12) Alternatively, the formation of complexes 25 and 26 may be
fast and reversible and the Curtin-Hammett principle may apply for
the rationalization of the selectivity.
(13) Knouzi, N.; Vaultier, M.; Carri e´ , R. Bull. Soc. Chim. Fr. 1985,
5, 815.

Chelation-Assisted Regioselective C-O Cleavage
J . Org. Chem., Vol. 64, No. 2, 1999 535
with the oxygen atom on the five-membered furanose
heterocycle may play a pivotal role in these reactions.
conditions gave 46 selectively in 75% yield. Presumably,
the reaction produces intermediate 47 which will further
react with MeMgI stereoselectively to yield 46. In a
Galactose derivative 38 was converted into the 4-hy-
droxy derivative 39 in 52% yield. Presumably, chelation
with the methoxy group at C
ity. The conformational rigidity may prohibit chelate
formation with oxygen atoms attached at C and C in
8.
6
controls the regioselectiv-
2
3
3
similar manner, the hydroxy group at C
3
in 44 can also
aid the regioselective ring opening of the acetonide at C
2
.
Accordingly, the reaction of 44 with MeMgI in refluxing
benzene afforded alcohol 49 in 55% yield. Intermediate
4
8 may be involved and further transformed into 49 by
excess MeMgI. The stereoselectivities in both reactions
can readily be rationalized by means of chelation with
the neighboring oxygen function.
Treatment of mannose derivative 40 with MeMgI in
refluxing benzene for 24 h afforded 41 in 51% yield.
Intermediate 42 was isolated when the same reaction
was carried out for 3 h.
Arabinose derivative 45 does not have a neighboring
oxygen atom for chelate formation with magnesium. In
addition, both acetonide rings are cis fused with the
perhydropyran ring. In a manner similar to that de-
scribed in eq 4, the least-hindered C-O bond in 45 was
cleaved selectively and the hemiacetal 51 thus generated
reacted with an additional mole of the Grignard reagent
to yield 50 stereoselectively.
Rea ction s a t th e An om er ic Cen ter . Stereoselective
displacement of one of the carbon-oxygen bonds by a
carbon-carbon bond at the anomeric center paves the
way for the synthesis of C-glycosides. The use of acetal
protective group for the anomeric hydroxy group abounds.
Accordingly, regioselective ring opening of the acetal
group at the anomeric carbon will generate a hemiacetal
which can further react with the nucleophile leading to
an alcohol stereoselectively. This idea was executed with
fructopyranose and arabinopyranose derivatives 43-45.
Con clu sion s
In summary, we have demonstrated a useful simple
procedure using the Grignard reagent to partially depro-
tect acetonides of vicinal diols leading to the correspond-
ing tert-butyl hydroxyalkyl ethers regioselectively. Che-
lation has played a pivotal role to direct the regioselectivity
of this ring opening process. The reaction offers a
powerful arsenal in selective protection-deprotection of
hydroxy groups in carbohydrates leading to various
monosaccharide derivatives having only one free hydroxy
group at the specific position.
Exp er im en ta l Section
Gen er a l P r oced u r e for Rea ction s of Aceton id es w ith
Gr ign a r d Rea gen t. To a solution of acetonide in benzene
under N was added, in one portion, the Grignard reagent (4
2
equiv). The mixture was stirred at 60 °C or heated under
reflux, and the reaction was monitored by TLC. The cooled
mixture was poured into water, and the organic layer was
By considering the structure of fructopyranose 43 the
separated. The aqueous solution was extracted with Et
the organic layers were washed with 10% aqueous NaOH,
water, and brine and dried (MgSO ). The solvent was evapo-
2
O, and
methoxy group at C
1
would assist the cleavage to occur
at C . Thus, treatment of 43 with MeMgI under usual
2
4

5
36 J . Org. Chem., Vol. 64, No. 2, 1999
Cheng et al.
rated in vacuo, and the residue was chromatographed on silica
gel to afford the product.
4.25 (q, J ) 6.6 Hz, 1 H), 4.61 (dt, J ) 4.8, 6.6 Hz, 1 H); 13C
NMR (CDCl , 75 MHz) δ 25.3, 26.1, 27.3, 38.6, 61.5, 65.5, 73.8,
3
2
-ter t-Bu toxy-2-p h en yleth a n ol (5a ). In a manner similar
to that described in the general procedure, a benzene solution
of 4a (310 mg, 1.2 mmol) with MeMgI (2.4 mL, 2.0 M in Et O,
.8 mmol) was refluxed for 20 h to give 5a 14 (300 mg, 89%):
75.2, 82.0, 109.6; HRMS calcd for C11
281.1058, found 281.1046.
H
21
O
6
3
S (M - CH )
2
A solution of the mesylate (2.3 g, 7.76 mmol) and sodium
azide (1.0 g, 15.4 mmol) in dry DMF (60 mL) was stirred at
130 °C for 24 h, cooled to room temperature, diluted with water
(300 mL), and extracted with ether (3 × 200 mL). The organic
4
1
H NMR (CDCl
3
, 300 MHz) δ 1.14 (s, 9 H), 2.26 (dd, J ) 3.8,
9
.4 Hz, 1 H), 3.45-3.52 (m, 2H), 4.60 (dd, J ) 4.5, 8.2 Hz, 1
1
3
H), 7.21-7.45 (m, 5 H); C NMR (CDCl
4.9, 75.4, 126.3, 127.3, 128.2, 142.2.
-ter t-Bu toxyocta n -1-ol (5b). In a manner similar to that
described in the general procedure, the reaction of 4b (438
mg, 2.4 mmol) with MeMgI (4.8 mL, 2.0 M in Et O, 9.6
mmol) in refluxing benzene for 20 h afforded 5b (343 mg,
3
, 50 MHz) δ 28.8, 67.8,
layer was washed with brine and dried (MgSO ), and the
4
7
solvent was evaporated in vacuo to give crude azide as a
-
1 1
2
colorless liquid (1.23 g, 65%): IR (neat) ν 2097 cm ; H NMR
(CDCl , 300 MHz) δ 1.13 (s, 9 H), 1.31 (s, 3 H), 1.40 (s, 3 H),
3
2
3.40-3.46 (m, 1 H), 3.53-3.63 (m, 2 H), 3.83-3.92 (m, 1 H),
1
5
13
3.97-4.06 (m, 2 H); C NMR (CDCl , 75 MHz) δ 25.2, 26.4,
3
1
7
0%): bp 80 °C (1 mmHg); H NMR (CDCl
t, J ) 6.8 Hz, 3 H), 1.18 (s, 9 H), 1.31-1.46 (m, 10 H), 2.07
3
, 200 MHz) δ 0.84
27.3, 62.3, 63.2, 66.6, 73.6, 75.1, 109.5; HRMS calcd for
(
(
(
7
2
C H O N (M - CH ) 228.1348, found 228.1340.
1
0
18
3
3
3
1
3
br s, 1 H), 3.36-3.40 (m, 1 H), 3.48-3.56 (m, 2 H); C NMR
CDCl , 50 MHz) δ 14.0, 22.6, 25.5, 28.7, 29.5, 31.8, 33.6, 65.2,
1.6, 73.9; HRMS calcd for C12 (M + 1) 203.2011, found
03.2021.
-ter t-Bu toxy-3-p h en ylp r op a n -1-ol (5c). In a manner
similar to that described in the general procedure, a mixture
of 4c (93 mg, 0.5 mmol) and MeMgI (1.0 mL, 2.0 M in Et O,
.0 mmol) was converted to 5c (84 mg, 80%): 1H NMR (CDCl
00 MHz) δ 1.14 (s, 9H), 1.90 (br q, J ) 6.0 Hz, 2 H), 3.05 (br
A suspension of the azide (2.0 g, 8.2 mmol) in absolute EtOH
70 mL) and Pd/C (10%, 200 mg) was stirred under an
atmosphere of H for 8 h. The reaction mixture was filtered
3
(
27 2
H O
2
over Celite and washed with EtOH. The solvent was removed
in vacuo, and the residue was chromatographed on silica gel
3
(2% MeOH in CHCl ) to afford 8 as a colorless liquid (1.41 g,
3
79%): [R]D26 -4.2° (c 5.0, CHCl ); IR (neat) v 3376, 3310 cm-1
2
3
;
2
2
3
,
1
H NMR (CDCl , 300 MHz) δ 1.14 (s, 9 H), 1.31 (s, 3 H), 1.37
3
(s, 3 H), 1.62 (s, 2 H), 2.96-3.02 (m, 1 H), 3.23 (dd, J ) 6.6,
9.0 Hz, 1 H), 3.46 (dd, J ) 6.6, 9.0 Hz, 1 H), 3.80-3.87 (m, 1
t, J ) 6.0 Hz, 1 H), 3.70 (br q, J ) 6.0 Hz, 2 H), 4.77 (br t, J
6.0 Hz, 1 H), 7.21-7.34 (m, 5H); 13C NMR (CDCl
, 50 MHz)
δ 28.6, 41.5, 60.9, 74.4, 75.1, 125.9, 126.8, 128.2, 145.4; HRMS
calcd for C13 208.1463, found 208.1468.
-Deoxy-O -ter t-bu tyl-D-th r eo-p en t-1-en ose Tr im eth -
)
3
H), 3.95-4.02 (m, 2 H); C NMR (CDCl , 75 MHz) δ 25.3, 26.6,
13
3
27.5, 53.3, 63.4, 66.1, 72.8, 77.5, 108.6; HRMS calcd for
H
20
5
O
2
C H O N (M
+
+ 1) 218.1756, found 218.1727.
1
1
24
3
2
1
,4-Bis-ter t-bu toxy-3(R)-a m in o-2(S)-bu ta n ol (9). To a
ylen e Dith ioa ceta l (7). In a manner similar to that described
in the general procedure, 6 (134 mg, 0.51 mmol) in benzene
solution of MeMgI in ether (1.8 mL, 2.0 M solution in ether)
was added 8 (100 mg, 0.46 mmol) under N atmosphere. The
2
(
20 mL) was allowed to react with MeMgI (2.0 mL, 2.0
ether was removed under reduced pressure. To this was added
dry benzene (5.0 mL), the resulting reaction mixture was
stirred at 60 °C for 48 h and cooled to room temperature, and
MeOH was added to quench the excess Grignard reagent. The
solvent was removed in vacuo, and the residue was chromato-
mmol) under refluxing conditions for 28 h to afford 7 (112 mg,
3
2
-1 1
7
8%): [R]
D
+7.7° (c 0.03, CHCl
, 300 MHz) δ 1.17 (s, 9 H), 2.09-2.16 (m, 2 H),
.77-2.95 (m, 5 H), 3.04 (d, J ) 3.2 Hz, 1 H), 3.36 (dd, J )
3
); IR (neat) ν 3443 cm ; H
NMR (CDCl
3
2
3
(
.5, 9.2 Hz, 1 H), 3.44 (dd, J ) 3.5, 9.2 Hz, 1 H), 3.52-3.54
graphed on silica gel (3% MeOH in CHCl
3
) to afford 9 as a
m, 1 H), 4.59-4.64 (m, 1 H), 5.91 (d, J ) 8.5 Hz, 1 H); 13
C
white solid (58 mg, 54%). Further crystallized from hexane to
NMR (CDCl
3.6, 129.7, 132.7; HRMS calcd for C12
78.1017.
3
, 75 MHz) δ 24.5, 27.4, 29.1, 29.4, 63.4, 70.0, 72.9,
25
yield colorless needles: mp 81-82 °C; [R]
D
+3.7° (c 1.5,
); IR (KBr) ν 3357, 3284, 3158 cm ; H NMR (CDCl
00 MHz) δ 1.13 (s, 18 H), 2.48 (s, 3 H), 2.93-2.99 (m, 1 H),
7
2
H
22
O
3
S
2
278.1010, found
-1
1
CHCl
3
3
,
3
3
7
1
3
4
O -ter t-Bu tyl-O ,O -isop r op ylid en e-L-th r eitol (11). A
13
.31-3.48 (m, 4 H), 3.59 (q, J ) 6.0 Hz, 1 H); C NMR (CDCl
3
,
solution of 10 (4.0 g, 19.8 mmol) and MeMgI (2 M solution in
ether, 4 equiv) in dry benzene (80 mL) was stirred at room
5 MHz) δ 27.4, 53.2, 63.2, 63.7, 72.6, 73.0; HRMS calcd for
+
C
12
H
28
O
H
3
N (M + 1) 234.2069, found 234.2055. Anal. Calcd
27 3
O N: C, 61.77; H, 11.66; N, 6.0. Found C, 61.28, H,
temperature for 5 days. Saturated NH
introduced, and the mixture was extracted with ether (3 ×
00 mL). The organic layer was washed with brine and dried
MgSO ), and the solvent was removed in vacuo. The residue
obtained was chromatographed on silica gel (hexane/EtOAc
4
Cl (50 mL) was
for C12
1
1.21, N, 5.38.
1
1
3
4
5
6
O -ter t-Bu t yl-O ,O -d im et h yl-O ,O -isop r op ylid en e-D-
m a n n itol (13). Under N atmosphere, to a benzene solution
40 mL) of 12 (0.87 g, 3.0 mmol) was added MeMgI (6 mL,
(
4
2
16
(
2
6
)
9/1) to afford 11 (2.1 g, 48%) as a colorless liquid: [R]
D
2
M in ether, 12 mmol). The mixture was refluxed for 22 h.
Cl (40 mL) was added, and the mixture was
-
1 1
+
4.9° (c 2.9, CHCl
3
3
); IR (neat) ν 3450 cm ; H NMR (CDCl ,
00 MHz) δ 1.11 (s, 9 H), 1.29 (s, 3 H), 1.35 (s, 3 H), 2.53 (br
Saturated NH
4
3
extracted with ether (40 mL × 3). The organic layer was
s, 1 H), 3.32 (dd, J ) 6.0, 8.9 Hz, 1 H), 3.38 (dd, J ) 6.0, 8.9
Hz, 1 H), 3.63 (q, J ) 6.0 Hz, 1 H), 3.78-3.83 (dd, J ) 6.0, 8.1
Hz, 1 H), 3.97-4.01 (dd, J ) 6.0, 8.1 Hz, 1 H), 4.11 (q, J ) 6.0
washed with NaOH (10%, 40 mL) and brine and then dried
(MgSO
4
). The solvent was evaporated in vacuo, and the residue
was chromatographed on silica gel (hexane/EtOAc 4/1) to give
1
3
Hz, 1 H); C NMR (CDCl
6
3
, 75 MHz) δ 25.2, 26.2, 27.3, 62.8,
27
1
3 as a colorless liquid (0.75 g, 82%): [R]
D
+12.5° (c 0.05,
, 300 MHz) δ 1.18 (s, 9 H), 1.32 (s, 3
H), 1.38 (s, 3 H), 2.64 (d, J ) 6.4 Hz, 1 H), 3.28 (dd, J ) 1.8,
.4 Hz, 1 H), 3.41 (s, 3H), 3.45 (dd, J ) 5.2, 8.9 Hz, 1 H), 3.50
s, 3 H), 3.55 (dd, J ) 3.6, 8.9 Hz, 1 H), 3.61 (dd, J ) 1.8, 6.3
Hz, 1 H), 3.73-3.82 (m, 1H), 3.94 (dd, J ) 6.3, 8.0 Hz, 1 H),
5.8, 71.2, 73.1, 76.9, 108.9; HRMS calcd for C10 (M -
CH ) 203.1283, found 203.1288.
3
(R)-Am in o-1-ter t-bu toxy-O ,O -isop r op ylid en e-3(S),4-
bu ta n ed iol (8). To an ice-cooled solution of 11 (1.84 g, 8.43
mmol) and Et N (1.71 g, 16.9 mmol) in CH Cl (30 mL) was
added a solution of MsCl (1.45 g, 12.6 mmol) in CH Cl (30
H
19
O
4
1
3 3
CHCl ); H NMR (CDCl
3
4
2
8
(
3
2
2
2
2
13
4
.06 (dd, J ) 6.3, 8.0 Hz, 1 H), 4.15 (q, J ) 6.3 Hz, 1 H);
NMR (CDCl , 75 MHz) δ 25.5, 26.6, 27.5, 60.1, 60.9, 62.1, 66.7,
9.3, 73.2, 75.9, 80.7, 80.8, 108.4. Anal. Calcd for C15
C, 58.80; H, 9.87. Found C, 58.65; H, 9.87.
O ,O -Bis-ter t-bu tyl-O ,O -dim eth yl-D-m an n itol (14). Un-
der N atmosphere, to a solution of MeMgI (30 mL, 1.7 M in
C
mL) dropwise over a period of 30 min. After the addition was
over, the reaction mixture was warmed to room temperature
and stirred for 24 h, and the reaction was then quenched with
3
6
30 6
H O :
HCl (10%). CH
layer was washed with NaOH (10%), water, and brine and
dried (MgSO ), and the solvent was evaporated in vacuo. The
2
Cl
2
(50 mL) was introduced, and the organic
1
6
3
4
2
4
residue was chromatographed on silica gel (hexane/EtOAc 9/1)
to yield the corresponding mesylate as a colorless liquid (2.3
(
14) Matsuda, M.; Sakatoku, S.; Higuchi, M.; Matsumura, H.; Yano,
2
6
1
W. Suzuka Kogyo Koto Semmon Gakko Kiyo 1977, 10, 151; Chem.
Abstr. 1978, 88, 104822.
g, 92%): [R]
δ 1.16 (s, 9 H), 1.33 (s, 3 H), 1.41 (s, 3 H), 3.10 (s, 3 H), 3.53
dd, J ) 4.8, 10.5 Hz, 1 H), 3.61 (dd, J ) 6.6, 10.5 Hz, 1 H),
.89 (dd, J ) 6.6, 9.0 Hz, 1 H), 4.05 (dd, J ) 6.6, 9.0 Hz, 1 H),
D
-6.0° (c 2.0, CHCl
3 3
); H NMR (CDCl , 300 MHz)
(15) Lauterbach, G.; Posselt, G.; Schaefer, R.; Schnurpfeil, D. J .
(
3
Prakt. Chem. 1981, 323, 101; Chem. Abstr. 1981, 95, 60913.
(16) Kuszmann, J . Carbohydr. Res. 1979, 71, 123.

Chelation-Assisted Regioselective C-O Cleavage
J . Org. Chem., Vol. 64, No. 2, 1999 537
2
3
toluene, 51 mmol) was added 12 (1.49 g in 10 mL toluene, 5.13
mmol). The mixture was refluxed for 72 h and worked up in a
similar manner as described above to give 14 as a colorless
silica gel (hexane/EtOAc 4/1) to give 22 (0.13 g, 86%): [R]
D
1
+7.0° (c 14.8, CHCl ); H NMR (CDCl3, 300 MHz) δ 1.18 (s, 9
H), 1.31 (s, 3 H), 1.35 (s, 3 H), 1.39 (s, 6 H), 2.14 (s, 1 H), 3.43
3
2
8
1
liquid (1.25 g, 76%): [R]
CDCl3, 300 MHz) δ 1.19 (s, 18 H), 2.67 (d, J ) 6.4 Hz, 2 H),
.46-3.53 (m, 10 H, embodied a singlet at δ 3.47 (6 H)), 3.58
dd, J ) 3.6, 8.8 Hz, 2 H), 3.76-3.84 (m, 2 H); 13C NMR (CDCl3,
D
+10.1° (c 0.07, CHCl
3
); H NMR
(d, J ) 6.1 Hz, 2 H), 3.80 (dt, J ) 2.6, 6.1 Hz, 1 H), 3.91-3.97
1
3
(
(m, 2 H), 3.99-4.05 (m, 2 H), 4.08-4.11 (m, 1 H); C NMR
(CDCl3, 75 MHz) δ 25.3, 26.6, 26.9, 27.2, 27.5, 63.7, 67.7, 69.7,
3
(
73.3, 77.1, 77.2, 80.3, 109.4, 109.7; HRMS calcd for C16
H
31
O
6
+
7
C
5 MHz) δ 27.5, 60.1, 62.2, 69.4, 73.1, 80.1; HRMS calcd for
(M + 1) 319.2120, found 319.2128.
H
35
O
6
(M + 1) 323.2433, found 323.2437.
3
4
5
6
2
1
16
O ,O ;O ,O -Bis-isopr opyliden e-O -ben zyl-O -ter t-bu tyl-
D-sor bitol (23). A THF solution (15 mL) of 22 (0.23 g, 0.72
mmol) was treated with NaH (0.07 g, 2.92 mmol) at room
temperature for 15 min followed by benzyl bromide (0.11 mL,
0.86 mmol). The mixture was stirred for 16 h, and saturated
2
3
5
O ,O -Isop r op ylid en e-O -ter t-b u t yl-D-xylose Diet h yl
Dith ioa ceta l (16a ). Following the general procedure, 15a (171
mg, 0.51 mmol) in benzene (20 mL) was allowed to react with
MeMgI (2.0 mL, 2.0 mmol) under 60 °C for 14 h to afford 16a
3
2
(
142 mg, 79%) [R]
D
-46.5° (c 0.05, CHCl
3
3
); IR (neat) ν 3479
NaHCO
washed with brine and dried (MgSO
removed in vacuo, and the residue was chromatographed on
3
(15 mL) was introduced. The organic layer was
-
1
1
cm ; H NMR (CDCl
two overlapping triplets, 6 H), 1.35 (s, 3 H), 1.38 (s, 3 H), 2.38
, 300 MHz) δ 1.12 (s, 9 H), 1.16-1.21
4
). The solvent was
(
2
4
(
3
2
d, J ) 6.2 Hz, 1 H), 2.59-2.71 (m, 4 H), 3.33-3.42 (m, 2 H),
silica gel (hexane/EtOAc 20/1) to give 23 (0.24 g, 82%): [R]
D
1
.76-3.79 (m, 1 H), 3.84 (d, J ) 5.4 Hz, 1 H), 4.08 (dd, J )
+26.9 (c 12, CHCl
3
3
), mp 65-67 °C; H NMR (CDCl , 300 MHz)
δ 1.18 (s, 9 H), 1.32 (s, 3 H), 1.35 (s, 6 H), 1.38 (s, 3 H), 3.55-
3.69 (m, 3 H), 3.82-3.86 (m, 1 H), 4.02-4.10 (m, 4 H), 4.60,
4.83 (AB q, J ) 11.7 Hz, 2 H), 7.21-7.36 (m, 5 H); C NMR
(CDCl3, 75 MHz) δ 25.3, 26.6, 26.8, 27.1, 27.5, 63.1, 67.6, 73.2,
73.4, 77.2, 80.5, 109.3, 109.5, 127.4, 127.6, 128.2, 128.4; HRMS
.7, 7.6 Hz, 1 H), 4.33 (dd, J ) 5.4, 7.6 Hz, 1 H); 13C NMR
3
(CDCl , 50 MHz) δ 14.3, 14.4, 25.0, 25.4, 27.1, 27.2, 27.5, 53.0,
1
3
6
3
3.7, 70.0, 73.4, 79.6, 79.7, 109.8; HRMS calcd for C16
52.1742, found 352.1750.
O ,O -Isop r op ylid en e-O -ter t-bu tyl-D-xylose Tr im eth -
H
32
O
4
S
2
2
3
5
ylen e Dith ioa ceta l (16b). In a manner similar to that
described in the general procedure, 15b (164 mg, 0.51 mmol)
in benzene (20 mL) was allowed to react with MeMgI (2.0 mL,
calcd for C23
H
3
36
O
4
6
408.2512, found 408.2522.
6
2
Allyl O ,O ;O ,O -Bis-isop r op ylid en e-r-D-glu cop yr a n o-
1
8
sid e (29). To a solution of allyl R-D-glucopyranoside (3.02 g,
13.7 mmol) in dry acetone (100 mL) was added TsOH (0.03 g,
0.16 mmol) and 2-methoxypropene (8 mL, 55 mmol), and the
2
.0 mmol) under 60 °C for 18 h to afford 16b (128 mg, 75%):
3
2
-1 1
[
(
R]
D
-13.9° (c 0.05, CHCl
3
3
); IR (neat) ν 3479 cm ; H NMR
CDCl
, 300 MHz) δ 1.18 (s, 9 H), 1.41 (s, 3 H), 1.43 (s, 3 H),
3
reaction was stirred for 2 h at 20 °C and quenched with Et N
(5 mL). The solvent was removed in vacuo, and the residue
was chromatographed on silica gel (EtOAc/hexane 1/9) to
1
.97-2.04 (m, 2 H), 2.35 (d, J ) 6.0 Hz, 1 H), 2.72-2.80 (m, 2
H), 2.90-2.98 (m, 2 H), 3.38-3.47 (m, 2 H), 3.80-3.83 (m, 1
H), 4.04 (d, J ) 5.4 Hz, 1 H), 4.09 (dd, J ) 2.7, 7.5 Hz, 1 H),
4
2
7
3
2
7
afford 29 (3.15 g, 76.6%) as a colorless oil: [R]
D
+86.6° (c
.41 (dd, J ) 5.4, 7.5 Hz, 1 H); 13C NMR (CDCl
, 75 MHz) δ
1
3
0.05, CHCl ); H NMR (CDCl , 200 MHz) δ 1.38 (s, 3 H), 1.39
3
3
5.7, 27.0, 27.1, 27.5, 28.7, 29.0, 47.7, 63.7, 70.0, 73.4, 78.8,
(s, 3 H), 1.42 (s, 3 H), 1.49 (s, 3 H), 3.45-3.59 (m, 2 H), 3.71-
3.88 (m, 3 H), 3.97-4.23 (m, 3 H), 5.11-5.18 (m, 2 H), 5.27 (d,
9.3, 110.0; HRMS calcd for C15
36.1417.
28 4 2
H O S 336.1429, found
1
3
J ) 17.2 Hz, 1 H), 5.89 (ddt, J ) 5.3, 10.9, 17.2 Hz, 1 H);
C
3
6
2
-Deoxy-O ,O -bis-ter t-bu tyl-D-a r a bin o-h exose Dieth yl
NMR (CDCl3, 50 MHz) δ 19.0, 26.3, 26.7, 28.9, 62.2, 65.0, 68.7,
73.7, 73.9, 76.7, 96.9, 99.5, 111.3, 117.4, 133.4. Anal. Calcd
Dith ioa ceta l (18). In a manner similar to that described in
the general procedure, 17 (178 mg, 0.51 mmol) in benzene (20
mL) was allowed to react with MeMgI (2.0 mL, 2.0 mmol)
under refluxing conditions for 34 h to give 18 (127 mg, 65%):
for C15
H
24
O
3
6
: C, 59.98; H, 8.05. Found C, 59.94; H, 8.12.
4
6
Allyl O -ter t-bu tyl-O ,O -isop r op ylid en e-R-D-glu cop y-
r a n osid e (30). The ethereal solution of MeMgI (2.4 mL, 2 M
ether, 6.1 mmol) was evacuated to remove ether, and the
residue was dissolved in benzene (175 mL). A solution of 29
(0.92 g, 3.06 mmol) in benzene (25 mL) was then added, the
mixture was stirred at 50-60 °C for 1.5 h, and the reaction
was quenched with NH Cl solution (50 mL). Organic layer was
separated, and the aqueous solution was extracted with ether
(200 mL). The combined organic layers were washed succes-
3
2
1
[R]
D
3 3
-17.1° (c 0.05, CHCl ); H NMR (CDCl , 300 MHz) δ
1
6
1
3
.20 (s, 9 H), 1.25 (s, 9 H), 1.21-1.32 (two overlapping triplets,
H), 1.93 (dt, J ) 7.2, 14.4 Hz, 1 H), 2.27 (ddd, J ) 6.2, 7.2,
4.4 Hz, 1 H), 2.52-2.74 (m, 4 H), 3.34 (d, J ) 5.0 Hz, 1 H),
.48-3.58 (m, 3 H), 3.62-3.68 (m, 2 H), 3.88 (t, J ) 7.2 Hz, 1
4
1
3
H), 4.17 (dt, J ) 2.5, 6.2 Hz, 1 H); C NMR (CDCl
δ 14.3, 14.4, 23.4, 24.4, 27.4, 28.7, 38.2, 47.7, 65.2, 69.7, 69.9,
7
3
3
, 75 MHz)
3.7, 73.8, 75.2; HRMS calcd for C18
82.2212.
H
38
O
4
S
2
382.2212, found
sively with water and brine and dried (MgSO ). Solvent was
removed in vacuo to yield the residue which was chromato-
graphed on silica gel (EtOAc/hexane 1/4) to afford 30 (0.83 g,
4
3
6
2
-Deoxy-O ,O -di-ter t-bu tyl-D-lyxo-h exose Dieth yl Dith io-
2
7
1
a ceta l (20). In a manner similar to that described in the
general procedure, 19 (179 mg, 0.51 mmol) in benzene (20 mL)
was allowed to react with MeMgI (2.0 mL, 2.0 mmol) under
86%) as a colorless oil: [R]
D
3
+110.8° (c 0.05, CHCl ); H NMR
(CDCl3, 200 MHz) δ 1.21 (s, 9 H), 1.37 (s, 3 H), 1.44 (s, 3 H),
2.06 (d, J ) 7.9 Hz, 1 H), 3.30-3.55 (m, 2 H), 3.55-3.88 (m, 4
H), 4.04 (dd, J ) 6.4, 12.8 Hz, 1 H), 4.22 (dd, J ) 5.4, 12.8 Hz,
1 H), 4.92 (d, J ) 3.8 Hz, 1 H), 5.21 (dd, J ) 1.5, 10.2 Hz, 1
H), 5.29 (dd, J ) 1.5, 17.3 Hz, 1 H), 5.92 (ddt, J ) 5.7, 10.2,
17.3 Hz, 1 H); 13C NMR (CDCl3, 50 MHz) δ 19.0, 29.0, 29.3,
62.5, 64.3, 68.5, 72.2, 72.4, 73.3, 74.5, 98.3, 99.1, 118.0, 133.6;
3
2
refluxing conditions for 18 h to give 20 (124 mg, 64%): [R]
D
-1 1
-
21.3° (c 0.02, CHCl
3
3
); IR (neat) ν 3447 cm ; H NMR (CDCl ,
3
6
2
00 MHz) δ 1.16 (s, 9 H), 1.18-1.22 (two overlapping triplets,
H), 1.23 (s, 9 H), 1.93-2.11 (m, 2 H), 2.51-2.73 (m, 4 H),
.96 (d, J ) 5.5 Hz, 1 H), 3.22 (d, J ) 3.6 Hz, 1 H), 3.43 (dd,
J ) 4.8, 9.1 Hz, 1 H), 3.50 (dd, J ) 4.8, 9.1 Hz, 1 H), 3.67-
28 6
HRMS calcd for C16H O 316.1886, found 316.1889.
.70 (m, 1 H), 3.83-3.91 (m, 2 H), 3.95-4.02 (m, 1 H); 13C NMR
CDCl , 75 MHz) δ 14.4, 24.0, 24.4, 27.4, 28.9, 39.8, 47.5, 63.7,
4
6
3
3
(
Allyl 2-a m in o-2-d eoxy-O ,O -isop r op ylid en e-O -ter t-
b u t yl-R-D-m a n n op yr a n osid e (31). Pyridine (1.5 mL, 19.0
mmol) was added at -10 °C to a solution of 30 (3.0 g, 9.5 mmol)
in CH Cl (60 mL). After brief stirring, Tf O (1.2 mL, 11.4
mmol) was slowly added over a period of 30 min, and the
mixture was stirred for 2 h at 0 °C. Cold water (20 mL) was
then introduced. The aqueous layer was extracted with ether
3
6
3
9.3, 72.2, 72.5, 73.4, 75.0; HRMS calcd for C18
82.2212, found 382.2209.
38 4 2
H O S
2
2
2
3
4
5
6
1
O ,O ;O ,O -Bis-isop r op ylid en e-O -ter t-b u t yl-D-sor b i-
1
7
tol (22). A benzene solution (25 mL) of 21 (0.15 g, 0.48 mmol)
was treated with MeMgI (2.0 mL, 2.0 mmol) under reflux for
5
h. After cooling, the mixture was diluted with ether and
quenched with saturated NH Cl. The organic layer was
washed with brine and dried (MgSO ). The solvent was
removed in vacuo and the residue was chromatographed on
4
(50 mL), and the combined organic layers were dried (MgSO ).
The solvent was removed in vacuo to yield the crude triflate
(3.6 g, 8.8 mmol, 93%) which was dissolved in DMF (60 mL).
4
4
3
NaN (2.86 g, 44.0 mmol) was added, and the mixture was
(
17) Pressman, B. C.; Anderson, L.; Lardy, H. A. J . Am. Chem. Soc.
(18) Talley, E. A.; Vale, M. D.; Yanovsky E. J . Am. Chem. Soc. 1945,
67, 2037.
1
950, 72, 2404.

5
38 J . Org. Chem., Vol. 64, No. 2, 1999
Cheng et al.
24 6
H O : C, 56.49;
stirred at 80 °C for 18 h. Then water was introduced, and the
mixture was extracted with ether (60 mL). The organic layer
was successively washed with water and brine and dried
79.6, 80.9, 103.8, 112.9. Anal. Calcd for C13
H, 8.75. Found: C, 56.00; H, 8.80.
3
6
1
2
O -ter t-Bu t yl-O -m et h yl-O ,O -isop r op ylid en e-r-D-ga -
4
(MgSO ). The solvent was removed in vacuo to give the residue
la ctop yr a n ose (39). In a manner similar to that described
2
1
which was chromatographed on silica gel (EtOAc/hexane 1:4)
to afford the corresponding azide (2.17 g, 72.3%) as a colorless
in the general procedure, a toluene solution of 38 (274 mg,
1.0 mmol) was treated with MeMgI (2.0 mL, 2.0 M in Et O,
4.0 mmol) at 60 °C for 40 h followed by usual workup to give
2
-
1
1
oil: [R]
NMR (CDCl
H), 3.50-4.05 (m, 7 H), 4.13 (ddt, J ) 1.2, 5.3, 12.9 Hz, 1
H), 4.50 (d, J ) 1.2 Hz, 1 H), 5.17-5.32 (m, 2 H), 5.88 (m, 1
D
29 +72.4° (c 0.05, CHCl
3
); IR (KBr) ν 2107 cm ; H
2
8
3
, 200 MHz) δ 1.22 (s, 9 H), 1.36 (s, 3 H), 1.49 (s,
39 (150 mg, 52%): [R]
D
+20.51° (c 0.4, CHCl
3
); IR (neat) ν
-
1 1
3
3443 cm ; H NMR (CDCl , 300 MHz) δ 1.23 (s, 9 H), 1.32 (s,
3
3 H), 1.48 (s, 3 H), 2.84 (d, J ) 2.9 Hz, 1 H), 3.37 (s, 3 H), 3.56
(dd, J ) 6.3, 10.0 Hz, 1 H), 3.64 (dd, J ) 5.8, 10.0 Hz, 1 H),
3.76 (t, J ) 4.5 Hz, 1 H), 3.80-3.84 (m, 1 H), 3.90-4.03 (m, 2
1
3
H); C NMR (CDCl
5.4, 68.1, 69.3, 70.2, 75.0, 98.4, 99.7, 117.9, 133.4. Anal. Calcd
for C16 : C, 56.29; H, 7.97; N, 12.31. Found C, 56.34;
3
, 50 MHz) δ 19.3, 28.4, 29.2, 62.2, 65.3,
6
H), 5.54 (d, J ) 1.0 Hz, 1 H); 13C NMR (CDCl
, 75 MHz) δ
26.5, 27.6, 28.5, 59.3, 67.2, 70.3, 71.8, 75.4, 97.3, 108.0. Anal.
Calcd for C H O : C, 57.91; H, 9.03. Found: C, 57.86; H,
H
27
N
3
O
5
3
H, 8.32; N, 12.14.
Triphenylphosphine13 (2.52 g, 9.60 mmol) was added to a
14 26
6
9
.01.
solution of the azide (3.27 g, 9.60 mmol) in THF (80 mL), and
the mixture was stirred for 2 h. Water (0.25 mL) was then
added, and the mixture was stirred at ambient temperature
for an additional 12 h. Hexane (50 mL) was introduced, and
the slurry was filtered. The filtrate was dried (MgSO
the solvent was removed in vacuo to give the residue which
was chromatographed on silica gel (EtOAc/hexane 1/2) to
2
4
Meth yl O ,O -Bis-ter t-bu tyl-r-D-m a n n op yr a n osid e (41).
In a manner similar to that described in the general procedure,
MeMgI (30 mmol, 30 mL in 1.0 M ether solution) was
2
2
evacuated to remove ether. A benzene solution (30 mL) of 40
(1.37 g, 5.0 mmol) was then introduced, and the reaction was
refluxed for 24 h, quenched with NH Cl, and extracted with
ether. The organic layer was washed with water and brine and
4
), and
4
2
9
afford 31 (2.34 g, 78%) as a colorless oil: [R]
CHCl
D
+57.4° (c 0.05,
1
dried (MgSO ). The solvent was removed in vacuo, and the
3
); H NMR (CDCl
3
, 200 MHz) δ 1.17 (s, 9 H), 1.35 (s, 3
4
H), 1.46 (s, 3 H), 3.11 (br, 1 H), 3.60-3.85 (m, 7 H), 3.39 (ddt,
J ) 1.2, 6.1, 13.0 Hz, 1 H), 4.13 (ddt, J ) 1.2, 5.2, 13.0 Hz, 1
H), 4.73 (br s, 1 H), 5.14-5.31 (m, 2 H), 5.89 (ddt, J ) 5.5,
1
2
1
residue was chromatographed on silica gel (hexane/EtOAc 7/3)
2
7
to yield 41 (0.78 g, 51%): mp 82-83 °C; [R]
D
+4.4°(c 2.5,
-
1
1
CHCl ); IR (KBr) ν 3439, 3377 cm ; H NMR (400 MHz,
CDCl ) δ 1.22 (s, 9 H), 1.23 (s, 9 H), 2.03 (t, J ) 6.4 Hz, 1 H),
3
0.4, 17.3 Hz, 1 H); 1 C NMR (CDCl
3
3
, 50 MHz) δ 19.2, 28.6,
9.2, 56.2, 62.5, 65.1, 67.9, 68.6, 69.8, 74.3, 99.5, 100.9, 117.3,
33.9. Anal. Calcd for C16 : C, 60.93; H, 9.27; N, 4.44.
3
2.09 (d, J ) 9.2 Hz, 1 H), 3.31 (s, 3 H), 3.48 (ddd, J ) 3.2, 5.2,
8.8 Hz, 1 H), 3.57 (dd, J ) 7.2, 8.8, Hz, 1 H), 3.65 (ddd, J )
4.0, 7.6, 9.2 Hz, 1 H), 3.71 (ddd, J ) 5.6, 7.2, 11.6 Hz, 1 H),
H
29NO
5
Found C, 60.92; H, 8.99; N, 3.95.
1
3
2
3
6
3.77-3.83 (m, 2 H), 4.60 (d, J ) 2.0 Hz, 1 H); C NMR (CDCl
3
,
Meth yl O -Meth yl-cO ,O -d i-ter t-bu tyl-R-D-glu cop yr a -
n osid e (33). In a manner similar to that described in the
general procedure, a benzene solution of 32 (280 mg, 0.92
mmol) and MeMgI (4.0 mL, 2.0 M in Et
refluxed for 48 h. After usual workup and chromatographic
separation (SiO , hexane/EtOAc 3/1), 33 was obtained (170 mg,
7
7
5 MHz) δ 28.5, 29.1, 54.8, 62.3, 69.5, 71.5, 71.6, 71.8, 74.8,
5.3, 101.1; HRMS calcd for C15 306.2042, found 306.2047.
30 6
H O
Anal. Calcd: C, 58.78; H, 9.87. Found: C, 58.77; H, 9.76.
2
O, 8.0 mmol) was
2
4
6
Met h yl O -ter t-Bu t yl-O ,O -isop r op ylid en e-r-D-m a n -
n op yr a n osid e (42). In a manner similar to that described in
the general procedure, a benzene solution (50 mL) of MeMgI
32.8 mmol) and 40 (500 mg, 1.82 mmol) was stirred at 40 °C
for 24 h. The mixture was cooled to room temperature, and
the reaction was quenched with NH Cl and extracted with
ether (3 × 50 mL). The organic layer was washed with brine
and dried (MgSO ). The residue obtained was chromato-
graphed over silica gel (hexane/EtOAc 4/1) to give, in addition
2
2
9
1
5
8%): [R]
D
3 3
+76.4° (c 0.01, CHCl ); H NMR (CDCl , 200 MHz)
(
δ 1.24 (s, 18 H), 1.79 (br, 1 H), 3.02 (dd, J ) 3.4, 9.4 Hz, 1 H),
3
1
.26 (t, J ) 9.0 Hz, 1 H), 3.37 (s, 3 H), 3.45 (s, 3 H), 3.57 (m,
H), 3.60-3.80 (m, 3 H), 4.80 (d, J ) 3.4 Hz, 1 H); 13C NMR
4
(CDCl
3
, 75 MHz) δ 29.2, 29.3, 54.8, 59.5, 62.4, 71.4, 72.6, 72.7,
4
7
3
5.3, 77.2, 82.1, 97.6; HRMS calcd for C16
20.2192.
H
32 6
O 320.2199, found
2
4
to 41 (120 mg, 23%), 42 (200 mg, 38%) as a colorless oil: [R]
D
1
2
3
6
O ,O -Isop r op ylid en e-O -m eth yl-O -ter t-bu tyl-r-D-glu -
-
1
1
+
3
2.3°(c 4.0, CHCl
00 MHz) δ 1.20 (s, 9 H), 1.33 (s, 3 H), 1.51 (s, 3 H), 3.37 (s, 3
H), 3.42 (d, J ) 1.7 Hz, 1 H), 3.52-3.61 (m, 2 H), 3.63-3.69
m, 2 H), 4.07-4.12 (m, 2 H), 4.86 (s, 1 H); 13C NMR (CDCl
,
3
3
3
); IR (neat) ν 3483 cm ; H NMR (CDCl ,
cofu r a n ose (35). In a manner similar to that described in
the general procedure, a benzene solution of 34 (274 mg, 1.0
mmol) was treated with MeMgI (3.0 mL, 2.0 M in Et
2
O, 6.0
(
mmol) under reflux for 12 h followed by usual workup to give
7
7
2
5 MHz) δ 26.1, 27.3, 27.9, 55.0, 63.9, 67.3, 72.7, 74.1, 75.1,
2
8
3
3
3
3
5 (140 mg, 55%): [R]
D
-29.9° (c 0.09, CHCl
3
3
); IR (neat) ν
8.0, 98.2, 109.5; HRMS calcd for C14
90.1732.
26 6
H O 290.1729, found
-
1 1
507 cm ; H NMR (CDCl , 200 MHz) δ 1.16 (s, 9 H), 1.29 (s,
H), 1.45 (s, 3 H), 2.79 (d, J ) 5.3 Hz, 1 H), 3.39 (m, 1 H),
.43 (s, 3 H), 3.58 (dd, J ) 3.2, 8.0 Hz, 1 H), 3.84 (d, J ) 2.9
Aceton id e 46. In a manner similar to that described in the
general procedure, a benzene solution (50 mL) of MeMgI (8.0
Hz, 1 H), 3.96 (m, 1 H), 4.05 (dd, J ) 2.9, 8.0 Hz, 1 H), 4.53 (d,
mmol) and 43 (520 mg, 2.0 mmol) was refluxed for 18 h
1
3
J ) 3.7 Hz, 1 H), 5.85 (d, J ) 3.7 Hz, 1 H); C NMR (CDCl3,
2
8
followed by usual workup to give 46 (460 mg, 75%): [R]
47.07° (c 0.09, CHCl
); mp 90-92 °C; IR (KBr) ν 3391 cm-1;
, 300 MHz) δ 1.14 (s, 3 H), 1.21 (s, 9 H), 1.34
s, 3 H), 1.39 (s, 3 H), 2.62 (t, J ) 5.2 Hz, 1 H), 3.09 (d,J ) 9.1
Hz, 2 H), 3.18 (s, 1 H), 3.36 (s, 3 H), 3.51 (d, J ) 9.2 Hz, 1 H),
D
7
8
5 MHz) δ 26.1, 26.6, 27.4, 57.95, 63.3, 67.8, 73.2, 79.7, 81.6,
4.0, 104.9, 111.5. Anal. Calcd for C14 : C, 57.91; H, 9.03.
+
3
26 6
H O
1
H NMR (CDCl
3
Found: C, 57.79; H, 9.13.
(
1
2
6
O ,O -Isopr opyliden e-O -ter t-bu tyl-r-D-allofu r an ose (37).
In a manner similar to that described in the general procedure,
13
3
.74 (m, 1 H), 4.00 (d, J ) 9.3 Hz, 1 H), 4.26 (m, 2 H);
NMR (75 MHz) δ 25.4, 28.1, 29.31, 58.9, 62.1, 69.8, 73.8, 75.7,
7.9, 78.3. Anal. Calcd for C15 C, 58.79; H, 9.87.
Found: C, 58.52; H, 9.79.
C
1
9
a benzene solution of 36 (260 mg, 1.0 mmol) was treated with
MeMgI (2.0 mL, 2.0 M in Et O, 4.0 mmol) under reflux for 20
h followed by usual workup to give 3720 (150 mg, 54%): [R]
23.1° (c 0.04, CHCl ); mp 59-61 °C; IR (KBr) ν 3491, 3364
, 200 MHz) δ 1.20 (s, 9 H), 1.34 (s, 3 H),
.56 (s, 3 H), 2.40 (d, J ) 4.2 Hz, 1 H), 3.48 (dd, J ) 4.8, 9.0
2
7
30 6
H O :
32
D
+
3
Aceton id e 49. In a manner similar to that described in the
general procedure, a benzene solution (50 mL) of MeMgI (4.0
-
1 1
cm ; H NMR (CDCl
3
1
mmol) and 44 (260 mg, 1.0 mmol) was refluxed for 18 h
Hz, 1 H), 3.64 (dd, J ) 3.4, 6.0 Hz, 1 H), 3.73 (d, J ) 4.7 Hz,
1
H), 4.64 (t, J ) 4.2 Hz, 1 H), 5.75 (d, J ) 3.7 Hz, 1 H);
NMR (CDCl , 75 MHz) δ 26.4, 26.7, 27.3, 62.7, 70.1, 70.9, 74.3,
28
followed by usual workup to give 49 (160 mg, 55%): [R]
D
H), 3.89 (dd, J ) 3.8, 9.0 Hz, 1 H), 3.98 (m, 1 H), 4.08 (m, 1
); mp 125-126 °C; IR (KBr) ν 3353 cm-1;
, 300 MHz) δ 1.15 (s, 3 H), 1.18 (s, 9 H), 1.37
s, 3 H), 1.49 (s, 3 H), 2.97 (dd, J ) 5.1, 7.7 Hz, 1 H), 3.07 (s,
+
1
1.85° (c 0.01, CHCl
3
1
3
C
H NMR (CDCl
3
3
(
(
19) (a) Collins, P. M. Tetrahedron 1965, 21, 1809. (b) Baker D. C.;
Horton D.; Tindall, C. G., J r. Carbohydr. Res. 1972, 24, 192.
20) Kawana, M.; Emoto, S. Bull. Chem. Soc. J pn. 1980, 53, 230.
(21) (a) Girard, P.; Kagan, H. Tetrahedron 1971, 27, 5911. (b)
Rathbone, E. B.; Stephen, A. M.; Pachler, K. G. R. Carbohydr. Res.
1971, 20, 357.
(

Chelation-Assisted Regioselective C-O Cleavage
H), 3.22 (d, J ) 8.6 Hz, 1 H), 3.39 (d, J ) 8.6 Hz, 1 H), 3.57
J . Org. Chem., Vol. 64, No. 2, 1999 539
3
3.72-3.73 (m, 2 H), 4.25 (q, J ) 6.0 Hz, 1 H), 4.31 (dd, J )
(t, J ) 8.5 Hz, 1 H), 3.70 (m, 3 H), 4.22 (dt, J ) 4.9, 9.0 Hz, 1
6.3, 7.8 Hz, 1 H); 13C NMR (CDCl
3
, 75 MHz) δ 21.3, 25.0, 27.6,
1
3
H), 4.42 (dd, J ) 1.5, 6.8 Hz, 1 H); C NMR (CDCl3, 75 MHz)
δ 20.2, 25.2, 27.2, 27.4, 61.6, 67.3, 72.1, 73.1, 73.6, 74.5, 78.1,
28.8, 61.4, 66.6, 72.2, 75.5, 76.6, 77.7, 107.9; HRMS calcd for
(M + 1) 263.1858, found 263.1857.
13 27 5
C H O
1
5
08.2. Anal. Calcd for C14
7.23; H, 9.63.
28 6
H O : C, 57.50; H, 9.66. Found: C,
Ack n ow led gm en t. Support from the National Sci-
ence Council of the Republic of China is gratefully
acknowledged.
Aceton id e 50. In a manner similar to that described in the
general procedure, a benzene solution (20 mL) of MeMgI (20
2
3
mmol) and 45 (1.15 g, 5.0 mmol) was refluxed for 24 h
followed by usual workup to give 50 (0.83 g, 63%): mp 62-63
2
7
-1 1
°
(
1
C; [R]
CDCl
.33 (s, 3 H), 1.42 (s, 3 H), 2.63 (br s, 2 H), 3.64-3.67 (m, 2 H),
D
+35.5°(c 4.5, CHCl
3
); IR (KBr) ν 3507 cm ; H NMR
Su p p or tin g In for m a tion Ava ila ble: NMR spectra for 5c,
7-9, 11, 14, 16a ,b, 18, 20, 22, 23, 29-31, 33, 42, and 50 and
the X-ray crystallographic data for 9 and 23 (36 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
3
, 300 MHz) δ 1.21 (d, J ) 7.2 Hz, 3 H), 1.23 (s, 9 H),
(
22) Stevens, C. L.; Glinski, R. P.; Taylor, K. G.; Sirokman, F. J .
Org. Chem. 1970, 35, 592.
23) (a) Heyns, K.; Neste, R.; Paal, M. Tetrahedron Lett. 1978, 42,
(
4
6
011. (b) De J ongh, D. C.; Biemann, K. J . Am. Chem. Soc. 1964, 86,
7.
J O981579A