Rapid synthesis of carbohydrate derivatives, including mimetics of C-linked disaccharides and C-linked aza disaccharides, using the hetero-Diels-Alder reaction

Article abstract of DOI:10.1021/jo101219w

In this work we demonstrate the value of performing a hetero-Diels-Alder reaction (HDAR) between Danishefsky's diene and a range of aldehydes or imines, under microwave irradiation. By using a range of aldehydes and imines, including those derived from carbohydrates, access to functionalized 2,3-dihydro-4H- pyran-4-ones or 2,3-dihydro-4-pyridinones in good to excellent synthetic yields is possible. A particular strength of the methodology is its ability to access mimetics of C-linked disaccharides and C-linked aza disaccharides, targets of current therapeutic interest, in a rapid, convenient, and diastereoselective manner. The effect of high pressure on the HDARs involving carbohydrate-derived aldehydes and imines is also explored, with enhancement in yields occurring for the aldehyde substrates. Finally, HDARs using carbohydrate derived ketones, enones, and enals are described under a range of conditions. Optimum results were obtained under high-pressure conditions, with highly functionalized carbohydrate derivatives being afforded, in good yields, in this way.

Full text of DOI:10.1021/jo101219w

pubs.acs.org/joc
Rapid Synthesis of Carbohydrate Derivatives, Including Mimetics
of C-Linked Disaccharides and C-Linked Aza Disaccharides,
Using the Hetero-Diels-Alder Reaction
Peter A. Burland,† David Coisson,‡ and Helen M. I. Osborn*,†
†Reading School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AD, United Kingdom,
and ‡Department of Chemistry, University of Reading, Whiteknights, Reading RG6 6AD, United Kingdom
h.m.i.osborn@rdg.ac.uk; þ44 (0)118 378 4644
Received July 19, 2010
In this work we demonstrate the value of performing a hetero-Diels-Alder reaction (HDAR)
between Danishefsky’s diene and a range of aldehydes or imines, under microwave irradiation. By
using a range of aldehydes and imines, including those derived from carbohydrates, access to
functionalized 2,3-dihydro-4H-pyran-4-ones or 2,3-dihydro-4-pyridinones in good to excellent
synthetic yields is possible. A particular strength of the methodology is its ability to access mimetics
of C-linked disaccharides and C-linked aza disaccharides, targets of current therapeutic interest, in a
rapid, convenient, and diastereoselective manner. The effect of high pressure on the HDARs
involving carbohydrate-derived aldehydes and imines is also explored, with enhancement in yields
occurring for the aldehyde substrates. Finally, HDARs using carbohydrate derived ketones, enones,
and enals are described under a range of conditions. Optimum results were obtained under high-
pressure conditions, with highly functionalized carbohydrate derivatives being afforded, in good
yields, in this way.
Introduction
In recent years the utility of microwave heating technology
to enhance synthetic chemistry transformations, including
cycloaddition reactions,3-6 has received considerable atten-
tion, with shorter reaction times, less decomposition of
sensitive materials, and the ability to perform multistep
reactions efficiently in one pot offering advantages for such
methodology. The value of using high pressure to enhance
the Diels-Alder and hetero-Diels-Alder reactions has also
been extensively documented in the literature with the yield
and the optical purity of synthetically useful products
generally being improved compared with more traditional
protocols.7
The hetero-Diels-Alder reaction (HDAR) has played a
pivotal role in the development of new synthetic methodol-
ogies for access to heterocycles, often with high regio-
and stereocontrol. For example, by using either a diene
or a dienophile that contains a heteroatom, access to dihy-
dropyrans or tetrahydropyridines,1 of considerable interest
within a range of biological applications,2 is possible.
(1) (a) Coisson, D.; Osborn, H. M. I. Mini Rev. Org. Chem. 2004, 1, 41.
(b) Pellissier, H. Tetrahedron 2009, 65, 2839–2877.
(2) (a) Tietze, L. F.; Rackelmann, N. Pure Appl. Chem. 2004, 76, 1967–
1983. (b) Chiacchio, U.; Padwa, A.; Romeo, G. Curr. Org. Chem. 2009, 13,
422–447.
In this program we have focused on the reaction of
aldehydes, ketones, and imines with Danishefsky’s diene to
afford dihydropyranone and tetrahydropyridine derivatives,
(3) For recent reviews see: (a) Kappe, C. O.; Dallinger, D. Mol. Diversity
2009, 13, 71–193. (b) Polshettiwar, V.; Varma, R. S. Chem. Soc. Rev. 2008, 37,
1546–1557. (c) Kappe, C. O. Chem. Soc. Rev. 2008, 37, 1127–1139.
(d) Kappe, C. O.; Dallinger, D. Nat. Rev. Drug Discovery 2006, 5, 51–63.
(4) (a) Pineiro, M.; Melo, T. M. V. D. P. E. Eur. J. Org. Chem. 2009, 31,
5287–5307. (b) de la Hoz, A.; Diaz-Ortis, A.; Moreno, A.; Langa, F. Eur. J.
Org. Chem. 2000, 22, 3659–3673.
(5) (a) Caddick, S.; Fitzmaurice, R. Tetrahedron 2009, 65, 3325–3355.
(b) Candeias, N. R.; Branco, L. C.; Gois, P. M.; Afonso, C. A. M.; Trindad,
A. F. Chem. Rev. 2009, 2703–2802. (c) Kappe, C. O. Chem. Soc. Rev. 2008,
37, 1127–1139. (d) de la Hoz, A.; Diaz-Ortiz, A.; Moreno, A. Chem. Soc. Rev.
2005, 34, 164–178. (e) Kappe, C. O. Angew. Chem., Int. Ed. 2004, 43, 6250–
6284.
(6) (a) Monbaliu, J. C.; Marchand-Brynaert, J. Synthesis 2009, 1876–
1880. (b) Nagarajan, S.; Barthes, C.; Gourdon, A. Tetrahedron 2009, 65,
3767–3772. (c) Castagnolo, D.; Botta, L.; Botta, M. Tetrahedron Lett. 2009,
50, 1526–1528. (d) Monbaliu, J.-C.; Marchand-Brynaert, J. Tetrahedron
Lett. 2008, 49, 1839–1842.
ꢀ
(7) (a) Benito-lopez, F.; Egberink, R. J. M.; Reinhoudt, D. N.; Verboom,
W. Tetrahedron 2008, 64, 10023–10040. (b) Ballerini, E.; Minuti, L.;
Piermatti, O.; Pizzo, F. J. Org. Chem. 2009, 74, 4311–4317. (c) Marrero,
J. G.; Harwood, L. M. Tetrahedron Lett. 2009, 50, 3574–3576.
7210 J. Org. Chem. 2010, 75, 7210–7218
Published on Web 10/12/2010
DOI: 10.1021/jo101219w
r
2010 American Chemical Society

Burland et al.
JOCArticle
SCHEME 1. The Diels-Alder Reaction Producing Pyranone 3
TABLE 1. Oxa-HDAR with Substituted Aldehydes
with particular emphasis on determining the value of micro-
wave irradiation on the efficiency of the methodology.
We have also applied the methodology to the synthesis
of carbohydrate mimetics, by incorporating aldehydes,
ketones, or imines appended to carbohydrate frameworks
as the dienophile, within the HDAR. In these cases the study
was extended to also examine the effect of high-pressure
conditions on the efficiency of the methodology. If such
methodology proved effective, access to C-linked disaccha-
ride and C-linked aza disaccharide mimetics, of interest as
inhibitors of glycosidase enzymes involved in a range of
disease processes, or as ligands for carbohydrate binding
processes involved in a range of diseases,8 would be achieved.
Results and Discussion
At the initial stage of the project a range of aromatic
and aliphatic aldehydes were selected as the dienophiles,
for reaction with Danishefsky’s diene, in order to access
structurally diverse dihydropyranones. Excellent literature
precedence exists for the HDAR of such systems in the
absence of microwave irradiation.4,9 The aldehydes utilized
in this program were therefore selected to probe the effect of
microwave irradiation on the efficiency of the reaction, as
well as expand the range of dihydropyranones previously
prepared with the conventional HDAR. In the experimental
protocol (see the Supporting Information) the reaction
mixture was heated to 30 °C under microwave irradiation
for 90 s. The mixture was then quenched by the addition
of trifluoroacetic acid, the solvents were removed in vacuo,
and the residue was purified by column chromatography.
Following the above procedure the compounds below were
synthesized from the corresponding aldehydes in excellent
synthetic yields, as summarized in Scheme 1 and Table 1.
For all substrates the reactions proceeded quickly afford-
ing the desired product in excellent yields after purification
by column chromatography on silica gel. Where the same
conversions had been reported using alternative reaction
conditions, the advantages of applying microwave irradia-
tion were evident. For example, for substrate 2b that
afforded dihydropyranone 3b in 83% yield after a reaction
time of 90 s, alternative reaction at -20 °C required
a prolonged reaction time of 72 h to afford the product in
a similar yield of 90% yield.10 In addition, formation of
dihydropyranone 3c had previously been reported in a lower
yield of 70%, with conventional conditions requiring reac-
tion at -78 °C for 2 h without microwave irradiation.11
Using the method described here the product was formed
in 94% yield after 90 s. Substrates 2e and 2f were utilized
in order to probe whether the chirality of the carbohydrate
framework could invoke any diastereocontrol during the
formation of the dihydropyran. However, 1H and 13C NMR
spectroscopic analysis of dihydropyranone 3e or 3f illus-
trated that each dihydropyranone was formed as a 1:1
mixture of diastereoisomers at C-2. Presumably for sub-
strates 2e and 2f, the chiral carbohydrate framework was
insufficiently close to the aldehyde functional group involved
in the HDAR to offer any stereocontrol.
In the next stage of the program the microwave-enhanced
HDAR using a range of imines was investigated. If successful
this would allow rapid access to tetrahydropyridinones.
Imines were prepared by reaction of the corresponding
aldehyde with benzylamine under anhydrous conditions
and these were used in two different protocols, specifically
a one-step protocol where the imine was reacted with
Danishefsky’s diene in situ, without any prior isolation of
the imine (method A), as well as a two-step protocol where
the imine was isolated and characterized first, before reac-
tion with the diene (method B). The results of these studies
are illustrated in Scheme 2 and Table 2. Substrates were
again chosen that would allow results to be compared with
the conventional HDAR, as well as to allow the efficiencies
of the oxa- and aza-HDARs to be compared.
(8) (a) de Melo, E. B.; Gomes, A. S.; Carvalho, I. Tetrahedron 2006, 62,
10277–10302. (b) Zhou, W. Curr. Top. Med. Chem. 2005, 5, 1363–1391.
(c) Compain, P.; Chagnault, V.; Martin, O. R. Tetrahedron: Asymmetry
2009, 20, 672–711.
(9) For example see: (a) Lowe, R. F.; Stoodley, R. J. Tetrahedron Lett.
1994, 35, 6351–6354. (b) Bednarski, M.; Danishefsky, S. J. J. Am. Chem. Soc.
1986, 108, 7060–7067.
(10) Keck, G. E.; Li, Y.-X.; Krishnamurthy, D. J. Org. Chem. 1995, 60,
5995–5999.
(11) Danishefsky, S. J.; Kerwin, J. F. J. Org. Chem. 1982, 47, 3183–3184.
J. Org. Chem. Vol. 75, No. 21, 2010 7211

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SCHEME 2. The Diels-Alder Reaction Producing Pyridinone 5
To determine whether high pressure could also be beneficial
for optimizing the yield of the HDARs, the HDAR with
substrates 2i-n were also performed at pressures of 19 kBar.
For comparative purposes, the HDAR was also performed with
neither microwave irradiation nor high-pressure conditions. The
results of this study are illustrated below in Table 3.
From Table 3 it can be seen that optimum results were
generally obtained with microwave irradiation. However,
reactions performed under high pressure generally afforded
higher yields of the desired products than by simply treating
the reactants with a Lewis acid at -78 °C to room temperature.
In general, for all reactions, improved yields of the desired
products were obtained when acetate groups were present at
C-2 and C-3 rather than benzyl ethers. Moreover, the mannose
substrates 2k and 2n afforded the poorest yields suggesting that
the axial C-2 substituent hinders the approach of the diene
onto the aldehyde. Indeed for substrate 2n no HDAR could be
effected in the absence of microwave irradiation or high-
pressure conditions. The reactions summarized in Table 3 were
generally highly stereoselective, with each reaction affording a
TABLE 2. Aza-HDAR with Substituted Aldehydes
1
single diastereoisomer, as evidenced by H and 13C NMR
spectroscopic analysis of crude reaction mixtures. However,
given the free rotation around the C-5,C-6 bond, it proved
impossible to determine the absolute stereochemistry of the
TABLE 3. Yields of the HDARs
As can be seen from Table 2, yields were good to excellent
with both the one-step and two-step approaches, but yields
were generally superior when the two-step protocol was
applied. For substrates 2a and 2b, the conventional HDAR
afforded 5a and 5b in yields of 84% and 51%, respectively.12
By comparing the results of the oxa- and aza-HDAR for
substrates 2a and 2b it is evident that both HDARs occur
with similar efficiency, despite the prerequisite for the for-
mation of an imine, from aldehyde 2a or 2b.
Having proved the validity of using microwave irradiation
to enhance the oxa- and aza-HDARs, attention next turned
to the feasibility of using more structurally complex alde-
hydes and imines, which incorporated carbohydrate frame-
works, within the methodology. If the HDARs with these
substrates were successful, facile entry to C-linked disaccha-
ride mimetics, including the more synthetically elusive aza
C-linked disaccharides, would be achieved.8 For the carbo-
hydrate derived aldehyde substrates 2i-n, an identical pro-
cedure to that described above for the oxa-HDAR with
aldehydes 2a-f was utilized. Pleasingly the proof of concept
results reported above proved extendable allowing entry to
the desired C-linked dihydropyrans 3i-n in generally good
to very good yields (Table 3).
aAddition of ZnCl2 and reaction under microwave irradiation
at 30 °C for 90 s. bHigh-pressure conditions involved reaction at
19 kbar using a Psika pressure system. cAddition of ZnCl2 and reaction
at -78 °C to room temperature for 7 h.
(12) Ali, T.; Chaunhan, K.; Frost, C. Tetrahedron Lett. 1999, 40, 5621–
5624.
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Burland et al.
JOCArticle
newly formed stereocenter at C-6, using NMR spectroscopic
techniques. The only substrate that afforded a 1:1 epimeric
mixture of products at C-6 was substrate 2j, and this only
afforded such an epimeric mixture when the reaction was
performed under microwave irradiation.
TABLE 4. Aza-HDAR with Carbohydrate Derived Imines under
Microwave Irradiation
To further functionalize the HDAR adducts and convert
them to closer mimics of natural disaccharide systems, reduc-
tion of the ketone functionality within the dihydropyranones
3i-n, to afford the corresponding alcohols 6i-n, was attempted
with use of Luche reduction conditions (Scheme 3).
SCHEME 3. Representative Luche Reduction of Dihydropyra-
none (3i) To Afford Alcohol (6i)
In all cases the reactions progressed successfully in excellent
synthetic yields (92-96%) that were in line with literature
precedent for similar reduction of pyranones, to afford single
diastereoisomers of C-linked disaccharide mimetics.13 To de-
termine the stereochemistry of the newly formed stereogenic
center at C-8, relative to that at C-6, a series of NOE experiments
were performed. These suggested that the hydrogens at C-6 and
C-8 were of a syn arrangement. The protecting groups within
6i-n are currently being removed within our laboratories,
affording tetrols ready for analysis of their ability to inhibit a
range of glycosidase enzymes.
To fully explore the value of this HDAR methodology
for preparing C-linked disaccharide mimetics, the utility of
the imines derived from aldehydes 2i-n in the one-step and
two-step aza-HDARs was next probed. Pleasingly these
substrates again proved effective precursors to C-linked
disaccharide mimetics, specifically C-linked aza disaccharide
mimetics. The best results were again obtained by using the
two-step HDAR protocol as when the one-step protocol was
utilized, a competing oxa-Diels-Alder reaction occurred,
presumably due to the reaction of the aldehydes with
Danishefsky’s diene before imine formation was complete.
For the two-step protocol, experimentation was required to
match the reactivity of the imine with solubility in solvents
appropriate for the HDAR; reaction of imines derived from
aniline, in DCM, proved optimal. Yields in these cases were
averagetovery goodandproductswereagainformed as single
diastereoisomers at C-6; interestingly when these reactions
were performed in the absence of microwave irradiation, or
under high-pressure conditions, no HDARs could be effected
with starting material being returned (Table 4).
were generally formed in comparable yields to the dihydro-
pyridinones 5i,5j,5l and 5n, respectively. However, the oxa-
HDAR proceeded in superior yields for substrates 2k and 2m
compared with the aza-HDAR by using imines 4k and 4m.
This reactivity illustrates that entry to C-linked aza disac-
charides derived from mannose is better achieved by using
the tri-O-benzyl protected imine 4n as opposed to the di-O-
acetyl protected imine 4k.
To conclude this program, a carbohydrate derived ketone 7a,
enone 7b, and enal 7c were next utilized within the oxa-HDARs
in an attempt to prepare spiro-carbohydrate derivatives. The
effectiveness of Lewis acid, high-pressure, and microwave irra-
diation on the reactions was again probed. Ketone 7a was
prepared according to a literature protocol,14 while ketones 7b
and 7c were formed with Swern oxidation protocols. Interesting
reactivity profiles were observed with high-pressure conditions,
as illustrated in Table 5. However, in contrast to the HDARs
From Table 4 it can be seen that optimum results were
generally obtained by using imines derived from methyl
glucopyranoside or methyl galactopyranoside rather than
methyl mannopyranoside. As observed before for the oxa-
HDARs (Table 3), improved yields of the desired products
were generally obtained when acetate groups were present at
C-2 and C-3 rather than benzyl ethers. It can be seen from
Tables 3 and 4 that the dihydropyranones 3i,3j,3l and 3n
(14) Jones, D. N.; Taylor, G. M.; Wood, W. Tetrahedron Lett. 1991, 13,
(13) Luche, J.-L. J. Am. Chem. Soc. 1978, 100, 2226–2227.
1667–1670.
J. Org. Chem. Vol. 75, No. 21, 2010 7213

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TABLE 5
(1H, ddd, J3a,5 1.0, J2,3a 3.5, J3a,3b 17.0, C(3a)H), 2.85 (1H, dd,
J2,3b 14.0, J3a,3b 17.0, C(3b)H), 5.42 (1H, dd, J2,3a 3.5, J2,3b
14.0, C(2)H), 5.53 (1H, dd, J3a,5 1.0, J5,6 6.0, C(5)H), 6.90-7.47
(4H, m, ArH), 7.55 (1H, d, J5,6 6.0, C(6)H); δc (CDCl3, 62.8
MHz) 43.7 (C-3), 80.5 (d, J 1.8, C-2), 107.1 (C-5), 113.5 (d,
J 22.8, C-20), 116.2 (d, J 20.7, C-40), 121.9 (d, J 3.1, C-60), 130.9 (d,
J 8.1, C-50), 140.7 (d, J 7.2, C-10), 163.3 (d, J 246.2, C-30), 163.3
(C-6), 191.9 (C-4); m/z (CI) 122 (10%), 163 (15%), 193 (MHþ,
17%); [C11H10FO2]þ requires 193.0665, found 193.0668.
2-Phenyl-2,3-dihydro-4H-pyran-4-one (3b): νmax (CHCl3, thin
film) 3062 (C;H), 1679 (CdC), 1595, 1403 (CdC), 1271, 1228,
1038 (C-O) cm-1; 1H NMR (CDCl3, 250 MHz) 2.60 (1H, ddd,
J
3-5 1.5, J3-2 3.5, J3-3 17.0, H3), 2.85 (1H, dd, J3-2 14.0, J3-3
17.0, H3), 5.36 (1H, dd, J2-3 3.5, J2-3 14.0, H2), 5.47 (1H, dd,
J5-3 1.0, J5-6 6.0, H5), 7.28-7.48 (6H, m, Ar-H, H6); 13C
NMR (CDCl3, 62.8 MHz) 42.34 (C3), 80.08 (C2), 106.33 (C5),
125.08-129.11 (Ar-C), 162.26 (C6); m/z (CI) MHþ (C11H11O2)
requires 175.0714, found 175.0754.
((E)-Propenyl)-2,3-dihydro-4H-pyran-2-one (3c): νmax (NaCl
disk/cm-1) 1680 s (CdO, stretch), 1640 m (CdC, stretching),
1435 m (CdC, stretch); δH (CDCl3, 250 MHz) 1.70 (3H, ddd,
J 1, J 1.5, J 2.5, CH3), 2.66-2.68 (2H, m, C(3)H), 4.53 (1H, dd,
J
2,3b 6.5, J2,3a 12.5, C(2)H), 5.50-5.59 (1H, m, RCHdCHCH3),
5.56 (1H, d, J5,6 6.0, C(5)H), 5.70-5.72 (1H, m, RCHdCHCH3),
7.62 (1H, d, J5,6 6.0, C(6)H); δC (CDCl3, 62.8 MHz) 18.0 (Me),
47.3 (C-3), 69.3 (C-2), 106.4 (C-5), 127.3 (RCdCCH3), 132.5
(RCdCCH3), 163.9 (C-6), 199.9 (C-4); m/z (CI) 111 (14%), 129
(4%), 138 (Mþ, 20%), 139 (MHþ, 72%); [C8H11O2]þ requires
139.0759, found 139.0754.
2,3,50,60-Tetrahydro-40H-[2,20]bipyranyl-4-one(3d): νmax (NaCl
disk/cm-1) 1755 s (CdO, stretch), 1654 m (CdC conjugated
double bond stretch), 1435 m (CdC stretch); δH (CDCl3,
250 MHz) 2.03-2.24 (2H, m, C(50)H), 2.48 (1H, ddd, J3a,5 1.0,
J2,3a 3.5, J3a,3b 16.5, C(3a)H), 2.73 (1H, dd, J2,3b 13.5, J3a,3b 16.5,
C(3b)H), 3.75-3.84 (2H, m, C(60)H), 4.19-4.22 (2H, m, C(40)H),
4.80 (1H, dd, J2,3a 3.5, J2,3b 13.5, C(2)H), 5.44 (1H, dd, J3a,5 1.0, J5.6
6.0, C(5)H), 5.94-5.97 (1H, m, C(30)H), 7.35 (1H, J5,6 6.0, C(6)H);
δC (CDCl3, 62.8 MHz) 25.2 (C-50), 40.7 (C-3), 64.4 (C-60), 65.0
(C-40), 80.4 (C-20), 107.6 (C-5), 124.2 (C-30), 134.3 (C-20), 163.1
(C-6), 192.4 (C-4); m/z (CI) 150 (19%), 163 (21%), 181 (MHþ,
100%), [C10H13O3]þ requires 181.0865, found 181.0861.
with aldehydes 2i-n, no reactions could be effected with 7a-c
with either conventional heating methodologies or microwave
irradiation but reactions did prove effective under high pressure
protocols. This reactivity profile presumably reflects both the
decreased reactivity of the ketone functional group compared
with the aldehyde functional group as well as increased steric
effects with ketones 7a-c.
For ketone 7a the HDAR proceeded as expected to afford
the spirocyclic carbohydrate 8a as a mixture of epimers at C-3.
In contrast, for enone 7b, a Diels-Alder reaction occurred
between the electron-deficient alkene within 7b and the
electron-rich Danishefsky’s diene, affording the cis-decalin
derivated structure 8b. The relative and absolute stereochem-
istry of the new structure was determined by NOE spectros-
copic analysis. For enal 7c the desired HDAR occurred
affording 8c as a mixture of epimers at C-6. The difference in
reactivity profiles between 7b and 7c presumably reflects the
enhanced reactivity of the aldehyde framework within enal 7c
over the ketone framework within enone 7b.
Acetic acid (2R,3R,4S,5R,6S)-4,5-diacetoxy-6-acetoxymethyl-
2-[2-nitro-4-(4-oxo-3,4-dihydro-2H-pyran-2-yl)phenoxy]tetra-
hydropyran-3-yl ester (3e): mp 87-88 °C; νmax (NaCl disk/
cm-1) 3024 m (C-H), 1740 s (CdO, carbonyl ester stretch),
1734 s (CdO, ketone stretch), 1648 m (CdC stretch), 1550 s
(nitro group stretch), 1145 s (R;O;CH3 stretch); δH
(CDCl3, 400 MHz) 1.97-2.10 (12H, m, CH3COR), 2.70
(1H, ddd, J3a,5 1.0, J2,3a 3.5, J3a,3b 17.0, C(3a)H), 2.85 (1H,
ddd, J3b,6 2.0, J2,3b 14.0, J3a,3b 17.0, C(3b)H), 3.89 (1H, ddd,
J 3.0, J 4.5, J 7.5, C(500)H), 4.21-4.30 (2H, m, C(600)H), 5.17
Conclusion
In conclusion this study has illustrated the potential of the
microwave-enhanced oxa- and aza-HDARs for rapid access to
dihydropyranones and tetrahydropyridinones under mild and
short reaction conditions. It has also demonstrated the value of
using high pressure to enhance the oxa-HDAR, particularly
where ketones or enals are used as substrates. In particular this
study has allowed access to carbohydrate derivatives including
mimetics of C-linked disaccharides and aza-C-linked disacchar-
ides in synthetically useful yields with high diastereoselectivity.
The elaboration of these targets to afford further mimetics of
aza-C-disaccharides is currently under investigation within our
laboratories and will be reported in due course.
(1H, d, J1 ,2 2.0, C(100)H), 5.24-5.27 (1H, m, C(400)H), 5.30
00 00
00
00 00
00 00
00 00
(1H, dd, J1 ,2 2.0, J2 ,3 8.5, C(2 )H), 5.34 (1H, dd, J2 ,3 8.5,
00 00
J3 ,4 9.0, C(300)H), 5.47 (1H, dd, J2,3a 3.5, J2,3b 14.0, C(2)H),
0
0
5.57 (1H, dd, J3a,5 1.0, J5,6 6.0, C(5)H), 7.40 (1H, dd, J5 ,6 2.0,
J 8.5, Ar(60)H), 7.49 (1H, d, J3b,6 2.0, J5,6 6.0, C(6)H),
7.53-757 (1H, m, Ar(30)H), 7.90 (1H, dd, J5 ,6 2.0, J 6.0,
Ar(50)H); δC (CDCl3, 100.4 MHz) 20.6-20.7 (4ꢀCH3COR),
43.1 (C-3), 61.7 (C-600), 68.0 (C-400), 70.4 (C-200), 72.2 (C-300),
72.4 (C-500), 79.1 (C-2), 100.1 (C-100), 100.1 (C-100), 107.9 (C-5),
120.3 (C-60), 120.3 (C-60), 123.0 (C-50), 131.1 (C-30), 131.1 (C-
30), 134.1 (C-40), 141.4 (C-10), 141.5 (C-10), 149.3 (C-20), 162.6
(C-6), 169.3 (CH3COOR), 170.5 (CH3COOR), 190.8 (C-4); m/
z (CI) 169 (39%), 331 (100%), 332 (15%), 566 (MHþ, 42%);
0
0
Experimental Section
[C25H28NO14]
þ requires 566.1510, found 566.1492.
2-(3-Fluorophenyl)-2,3-dihydro-4H-pyran-4-one (3a): νmax
(NaCl disk/cm-1) 3045 m (Ar, C;H), 1684 s (CdO, ketone
stretch), 1634 m (CdC stretch); δH (CDCl3, 250 MHz) 2.62
Acetic acid (2R,3R,4S,5R,6S)-4,5-diacetoxy-6-acetoxymethyl-
2-[2-nitro-4-(4-oxo-3,4-dihydro-2H-pyran-2-yl)phenoxy]tetra-
hydropyran-3-yl ester (3f): νmax (NaCl disk/cm-1) 3035 m
7214 J. Org. Chem. Vol. 75, No. 21, 2010

Burland et al.
JOCArticle
(C-H), 1745 s (CdO, carbonyl ester stretch), 1720 s (CdO,
ketone stretch), 1655 m (CdC, stretch), 1140 s (R;O;CH3,
stretch); δH (CDCl3, 250 MHz) 1.97-2.10 (12H, m, CH3COR),
2.67 (1H, ddd, J3a,5 1.0, J2,3a 3.5, J3a,3b 16.5, C(3a)H), 2.90 (1H,
dd, J2,3b 14.0, J3a,3b 16.5, C(3b)H), 3.91 (1H, ddd, J 3.5, J 5.0,
169.8 (COCH3), 170.0 (COCH3), 192.5 (C8); m/z (CI) MNaþ
(C22H26O9Na) requires 457.1475, found 457.1469.
Methyl 2,3,4-tri-O-benzyl-6,7-dihydropyran-8-one glucopyra-
nose (3l): [R]20D þ64.2 (c 1.01, CHCl3); νmax (CHCl3, thin film)
2916 (C;H), 2091, 1650 (CdO), 1441 (C;H), 1357, 1276, 1093
1
J 7.5, C(500)H), 4.21-4.30 (2H, m, C(600)H), 5.14 (1H, d, J1 ,2
(C;O) cm-1; H NMR (CDCl3, 400.1 MHz) 2.21 (1H, ddd,
00 00
2.0, C(100)H), 5.24-5.27 (1H, m, C(400)H), 5.26 (1H, dd, J1 ,2
J7-9 1.0, J7-6 3.5, J7-7 17.0, H7), 2.97 (1H, dd, J7-6 15.0, J7-7
00 00
2.0, J2 ,3 7.5, C(200)H), 5.31 (1H, dd, J2 ,3 7.5, J3 ,4 8.5,
17.0, H7), 3.34 (3H, s, OCH3), 3.54-3.57 (2H, m, H2, H5), 3.74
(1H, t, J4-3 = J4-5 10.0, H4), 4.01 (1H, t, J3-2 = J3-4 10.0, H3),
4.59-4.67 (4H, m, H1, H6, 2ꢀBnCH2), 4.80-4.91 (3H, m,
3ꢀBnCH2), 5.01 (1H, d, J 7.0, BnCH2), 5.36 (1H, dd, J9-7 1.0,
00 00
00 00
00 00
C(300)H), 5.47 (1H, dd, J2,3a 3.5, J2,3b 14.0, C(2)H), 5.57 (1H,
dd, J3a,5 1.0, J5,6 5.5, C(5)H), 7.05 (1H, d, J5 ,6 J 8.0, Ar(60)H),
0
0
0
0
0
7.08 (1H, d, J2 ,3 7.0, Ar(2 )H), 7.49 (1H, d, J5,6 5.5, C(6)H), 7.42
(1H, d, J2 ,3 7.0, Ar(30)H), 7.45 (1H, J5 ,6 8.0, Ar(50)H); δC
(CDCl3, 100.4 MHz) 20.6-20.7 (4ꢀCH3COR), 43.2 (C-3), 61.9
(C-600), 68.2 (C-400), 71.0 (C-200), 72.1 (C-300), 72.6 (C-500), 80.5
(C-2), 80.6 (C-2), 98.9 (C-100), 107.4 (C-5), 117.2 (C-60 and
C-20), 127.7 (C-50 and C-30), 132.0 (C-40), 140.4 (C-10), 163.3
(C-6), 169.3-170.8 (CH3COOR), 192.8 (C-4); m/z (CI) 553
(MHþ, 42%), 456 (M - C5H5O2, 43%); [C27H37O12]þ requires
553.2287, found 553.2277.
J
9-10 6.0, H9), 7.15 (1H, d, J10-9 6.0, H10), 7.22-7.39 (15H, m,
0
0
0
0
Ar-H); 13C NMR (CDCl3, 100.6 MHz) 37.9 (C7), 55.3 (OCH3),
70.3 (C5), 73.5 (ArCH2), 75.1 (ArCH2), 75.5 (C6), 75.8 (C4),
75.9 (ArCH2), 79.6 (C2), 82.2 (C3), 98.4 (C1), 107.1 (C9),
127.8-128.5 (Ar-C), 162.6 (C10), 192.6 (C8); m/z (CI) MNaþ
(C32H34O7Na) requires 553.2197, found 553.2197.
Methyl 2,3,4-tri-O-benzyl-6,7-dihydropyran-8-one galacto-
pyranoside (3m): [R]20 -5.1 (c 1.0, CHCl3); νmax (CHCl3,
D
Methyl 2,3-di-O-acetyl-4-O-benzyl-6,7-dihydropyran-8-one
thin film) 2916 (C;H), 1675 (CdC), 1598 (CdO), 1496, 1453
(C;H), 1402, 1353, 1272, 1096 (C;O), 1046 cm-1; 1H NMR
(CDCl3, 400.1 MHz) 2.45 (1H, dd, J7-6 13.0, J7-7 17.0, H7),
2.72 (1H, ddd, J7-9 1.0, J7-6 4.0, J7-7 17.0, H7), 3.32 (1H, s,
OCH3), 3.77 (1H, dd, J5-4 0.5, J5-6 9.0, H5), 3.94 (1H, dd, J3-4
3.0, J3-2 10.0, H3), 4.04 (1H, dd, J2-1 3.5, J2-3 10.0, H2), 4.08
(1H, dd, J4-5 0.5, J4-3 3.0, H4), 4.53 (1H, ddd, J6-7 4.0, J6-5
9.0, J6-7 13.0, H6), 4.62-4.70 (3H, m, H1, 2ꢀBnCH2), 4.79
(1H, d, J 12.0, 1ꢀBnCH2), 4.85 (1H, d, J 12.0, 1ꢀBnCH2), 4.91
(1H, d, J 12.0, 1ꢀBnCH2), 5.35 (1H, dd, J9-7 1.0, J9-10 6.0,
H9), 7.01 (1H, d, J10-9 6.0, H10), 7.26-7.41 (15H, m, Ar-H);
13C NMR (CDCl3, 100.1 MHz) 38.6 (C7), 55.5 (OCH3), 70.5
(C5), 73.2 (C4), 73.6 (BnCH2), 73.7 (BnCH2), 74.8 (BnCH2),
75.6 (C6), 76.2 (C2), 78.9 (C3), 99.0 (C1), 107.6 (C9), 127.5-
128.6 (Ar-C), 138.2-138.6 (Ar-C), 161.9 (C10), 191.9
(C8); m/z (CI) MHþ (C32H34O7Na) requires 553.2202, found
553.2203.
glucopyranoside (3i): [R]20 þ27.0 (c 1.0, CHCl3); νmax
D
(CHCl3, thin film) 2916 (C;H), 1749 (CdC), 1678 (CdO),
1595, 1369 (C;H), 1240, 1055 (C;O) cm-1 1H NMR
;
(CDCl3, 400 MHz) 2.02 (3H, s, COCH3), 2.08 (3H, s, COCH3),
2.25 (1H, ddd, J7-9 1.0, J7-6 3.5, J7-7 17.0, H7), 3.01 (1H, dd,
J
7-6 14.5, J7-7 17.0, H7), 3.35 (3H, s, OCH3), 3.67 (1H, d, J5-4
9.5, H5), 3.90 (1H, t, J4-3 = J4-5 9.5, H4), 4.55 (1H, d, J 11.5,
1ꢀBnCH2), 4.63-4.69 (2H, m, H6, 1ꢀBnCH2), 4.86 (1H, dd,
J
2-1 3.5, J2-3 10.0, H2), 4.93 (1H, d, J1-2 3.5, H1), 5.39 (1H,
dd, J9-7 1.0, J9-10 7.0, H9), 5.56 (1H, dd, J3-4 9.5, J3-2 10.0,
H3), 7.21-7.36 (6H, m, Ar-H, H10); 13C NMR (CDCl3, 100.6
MHz) 20.8 (COCH3), 20.9 (COCH3), 37.8 (C7), 55.3 (OCH3),
70.3 (C5), 71.0 (C2), 72.3 (C3), 74.6 (C4), 74.9 (BnCH2), 75.2
(C6), 97.0 (C1), 107.2 (C9), 128.2-128.6 (Ar-C), 162.3 (C10),
169.8 (COCH3), 170.4 (COCH3), 192.2 (C8); m/z (CI) MNaþ
(C22H26O9Na) requires 457.1469, found 457.1468.
Methyl 2,3-di-O-acetyl-4-O-benzyl-6,7-dihydropyran-8-one
galactopyranoside (3j): νmax (CHCl3, thin film) 2924 (C-H),
1744 (CdC), 1666 (CdO), 1600, 1440 (C;H), 1359, 1225,
1047 (C;O) cm-1; 1H NMR (CDCl3, 250 MHz) 2.06 (3H, s,
COCH3), 2.07 (3H, s, COCH3), 2.56 (1H, app s, H7), 2.79 (1H,
dd, J7-6 5.0, J7-7 7.5, H7), 3.34 (3H, s, OCH3), 3.73 (3H, s,
OCH3), 3.95 (1H, app d, J5-6 10.0, H5), 4.23 (1H, app s, H4),
4.50-4.61 (3H, m, H6, BnCH2), 4.99 (1H, d, J1-2 2.5, H1),
5.32-5.33 (2H, m, H2, H3), 5.41 (1H, d, J9-10 5.0, H9), 5.62
(1H, d, J9-10 12.5, H9), 7.13 (1H, d, J10-9 5.0, H10), 7.28-7.33
(5H, m, Ar-H), 7.63 (1H, d, J10-9 12.5, H10); 13C NMR
(CDCl3, 100.6 MHz) 20.90 (COCH3), 21.10 (COCH3), 38.35
(C7), 55.50 (OCH3), 57.53 (OCH3), 68.61 (C2/C3), 69.87 (C5),
70.45 (C2/C3), 73.66 (C4), 75.37 (BnCH2), 97.34 (C1), 106.67
(C9), 107.67 (C9), 128.11-131.02 (Ar-C), 162.16 (C10),
163.95 (C10); m/z (CI) MHþ (C22H27O9) requires 435.1650,
found 435.1646.
Methyl 2,3,4-tri-O-benzyl-6,7-dihydropyran-8-one mannopyr-
anoside (3n): [R]20D þ58.2 (c 1.0, CHCl3); νmax (CHCl3, thin film)
3435, 2914 (C;H), 1677 (CdC), 1595 (CdO), 1453, 1403, 1361,
1276, 1124 (C;O;C), 1068 (C;O) cm-1; 1H NMR (CDCl3,
400.1 MHz) 2.22 (1H, ddd, J7-9 1.0, J7-6 3.5, J7-7 15.0, H7),
3.08 (1H, dd, J7-7 15.0, J7-6 17.0, H7), 3.27 (3H, s, OCH3),
3.48-3.52 (1H, m, H5), 3.80 (1H, dd, J2-1 2.0, J2-3 3.0, H2),
3.87 (1H, dd, J3-2 3.0, J3-4 9.5, H3), 4.23 (1H, t, J4-3 = J4-5 9.5,
H4), 4.61-4.66 (1H, m, 1ꢀBnCH2), 4.70-4.77 (4H, m,
2ꢀBnCH2, H1, H6), 4.96 (1H, d, J 11.0, 1ꢀBnCH2), 5.38 (1H,
dd, J9-7 1.0, J9-10 6.0, H9), 7.24-7.37 (16H, m, Ar-H, H10);
13C NMR (CDCl3, 100.6 MHz) 38.2 (C7), 55.1 (OCH3), 71.9
(C5), 72.4 (BnCH2), 73.1 (BnCH2), 73.3 (C4), 74.1 (C2), 75.5
(BnCH2), 76.0 (C6), 80.8 (C3), 100.0 (C1), 107.1 (C9),
127.8-128.7 (Ar-C), 163.6 (C10), 193.5 (C8); m/z (CI) MNaþ
(C32H34O7Na) requires 553.2202, found 553.2197.
1-Benzyl-2-(3-fluorophenyl)-2,3-dihydropyridin-4-one (5a).
νmax (CHCl3, thin film) 3029 (C;H), 2919 (C;H), 1638
(CdO), 1594, 1486, 1449 (C;N), 1383, 1213, 1165 cm-1; 1H
NMR (CDCl3, 400 MHz) 2.63 (1H, dd, J3-2 7.0, J3-3 16.5,
H3), 2.87 (1H, dd, J3-2 7.0, J3-3 16.5, H3), 4.13 (1H, d, J 15.0,
BnCH2), 4.38 (1H, d, J 15.0, BnCH2), 4.50 (1H, t, J2-3 = J2-3
7.0, H2), 5.09 (1H, d, J5-6 7.5, H5), 6.96-7.37 (9H, m, Ar-H);
13C NMR (CDCl3, 100.4 MHz) 43.39 (C3), 57.54 (BnCH2),
60.05 (C2), 98.96 (C5), 113.90 (d, J 22.0, C20), 115.34 (d, J 21.0,
C40), 122.70 (d, J 2.9, C60), 127.71-129.05 (Ar-C), 130.76
(d, J 8.2, C50), 141.17 (d, J 6.6, C10), 154.04þ(C6), 163.06 (d,
J 246.0, C30), 189.84 (C4); m/z (CI) MH (C18H17FNO)
requires 282.1289, found 282.1286.
Methyl 2,3-di-O-acetyl-4-O-benzyl-6,7-dihydropyran-8-one
mannopyranoside (3k): νmax (CHCl3, thin film) 3440, 2932
(C-H), 1750, 1678 (CdC), 1597 (CdO), 1405, 1369, 1244,
1137 (C;O;C), 1085 (C;O) cm-1; 1H NMR (CDCl3, 400.1
MHz) 2.00 (3H, s, COCH3), 2.17 (3H, s, COCH3), 2.27 (1H,
ddd, J7-9 1.0, J7-6 3.5, J7-7 17.0, H7), 3.07 (1H, dd, J7-6 15.0,
J
7-7 17.0, H7), 3.36 (3H, s, OCH3), 3.67 (1H, dd, J5-6 1.5, J5-4
10.0, H5), 4.12 (1H, t, J4-3 = J4-5 10.0, H4), 4.59 (1H, d,
J 11.5, 1ꢀBnCH2), 4.72-4.76 (4H, m, H1, H6, 1ꢀBnCH2),
5.29 (1H, dd, J2-1 1.5, J2-3 3.5, H2), 5.34 (1H, dd, J3-2 3.5,
J3-4 10.0, H3), 5.42 (1H, dd, J9-7 1.0, J9-10 6.0, H9),
7.24-7.37 (6H, m, H10, Ar-H); 13C NMR (CDCl3, 100.1
MHz) 20.9 (COCH3), 21.0 (COCH3), 37.9 (C7), 55.3 (OCH3),
69.7 (C2), 71.3 (C5), 71.6 (C4), 72.1 (C3), 75.1 (BnCH2), 75.5
(C6), 99.1 (C1), 107.4 (C9), 127.9-128.6 (Ar-C), 162.6 (C10),
1-Benzyl-2-phenyl-2,3-dihydropyridin-4-one (5b): νmax (CHCl3,
thin film) 3028 (C;H), 1636 (CdO), 1576, 1451 (C;N), 1381,
1357, 1204, 1158; 1H NMR (CDCl3, 250 MHz) 2.69 (1H, dd, J3-2
J. Org. Chem. Vol. 75, No. 21, 2010 7215

Burland et al.
JOCArticle
8.0, J3-3 16.5, H3), 2.86 (1H, dd, J3-2 8.0, J3-3 16.5, H3), 4.13
(1H, d, J 15.0, BnCH2), 4.34 (1H, d, J 15.0, BnCH2), 4.50 (1H, t,
J2-3 = J3-2 8.0, H2), 5.10 (1H, d, J5-6 7.5, H5), 7.23-7.46 (11H,
m, Ar-H, H6); 13C NMR (CDCl3, 62.8 MHz) 29.43 (C3), 43.97
(BnCH2), 61.04 (C2), 99.00 (C5), 127.52-129.48 (Ar-C), 154.87
(C6), 190.95 (C4); m/z (CI) MHþ (C18H18NO) requires 264.1388,
found 264.1378.
N-Phenyl methyl 2,3,4-tri-O-benzyl-6,7-dihydropyridin-8-one
mannopyranose (5k): [R]20 -110.1 (c 0.68, CHCl3); νmax
D
(CHCl3, thin film) 2921 (C;H), 1751 (CdC), 1638 (CdO),
1584, 1489 (C;N), 1363, 1220, 1134 (C;O;C), 1076 (C;O)
cm-1; 1H NMR (CDCl3, 400.1 MHz), 1.82 (3H, s, OCH3), 2.16
(3H, s, OCH3), 2.73 (1H, app d, J7-7 17.0, H7), 3.20-3.37 (4H,
m, OCH3, H7), 3.49 (1H, dd, J4-3 8.5, J4-5 10.0, H4), 3.74 (1H,
d, J 11.5, BnCH2), 3.75 (1H, dd, J5-6 2.0, J5-4 9.5, H5), 4.34 (1H,
d, J 11.5, BnCH2), 4.63 (1H, app s, H1), 4.73 (1H, app d, J 9.5,
H6), 5.16-5.19 (2H, m, H2, H3), 5.38 (1H, d, J9-10 7.5, H9),
7.12-7.43 (11H, m, Ar-C, H10); 13C NMR (CDCl3, 100.6
MHz) 20.80 (COCH3), 20.93 (COCH3), 39.58 (C7), 55.78
(OCH3), 56.83 (C6), 69.85 (C2), 72.68 (C3), 73.58 (BnCH2),
73.93 (C4), 74.89 (C5), 122.92-129.91 (Ar-C), 169.52
(COCH3), 169.62 (COCH3); m/z (CI) MHþ (C28H32O8N) re-
quires 510.2128, found 510.2119.
1-Benzyl-2-pentyl-2,3-dihydropyridin-4-one (5g): νmax (CHCl3,
thin film) 2927 (C;H), 2857, 1697, 1616 (CdO), 1518, 1451 (C;
1
N), 1403, 1205, 1155 cm-1; H NMR (CDCl3, 400 MHz) 0.87
(3H, t, J 7.0, H11), 1.19-1.32 (5H, m, 1ꢀH8, H9, H10),
1.35-1.44 (1H, m, H8), 1.55-1.64 (1H, m, H7), 1.77-1.87
(1H, m, H7), 2.65 (1H, dd, J3-2 2.0, J3-3 17.0, H3), 2.87 (1H,
dd, J3-2 7.5, J3-3 17.0, H3), 3.47-3.51 (1H, m, H2), 4.43 (1H, d,
J 15.0, BnCH2), 4.53 (1H, d, J 15.0, BnCH2), 5.39 (1H, d, J5-6 7.0,
H5), 7.33 (1H, d, J6-5 7.0, H6), 7.25-7.44 (5H, m, Ar-H); 13
C
N-Phenyl methyl 2,3,4-tri-O-benzyl-6,7-dihydropyridin-8-one
glucopyranose (5l): [R]20D þ15.3 (c 0.79, CHCl3); νmax (CHCl3,
thin film) 2916 (C;H), 1651 (CdO), 1584, 1494, 1454 (C-N),
1258, 1208, 1090 (C;O) cm-1; 1H NMR (CDCl3, 400.1 MHz)
2.52 (1H, d, J 16.5, H7), 3.15 (1H, dd, J7-6 8.5, J7-7 16.5, H7),
3.21 (1H, dd, J4-3 9.0, J4-5 10.0, H4), 3.36 (3H, s, OCH3), 3.41
(1H, d, J 11.5, 1ꢀBnCH2), 3.47 (1H, dd, J2-1 3.5, J2-3 10.0, H2),
3.77 (1H, dd, J5-6 2.5, J5-4 10.0, H5), 3.87 (1H, dd, J3-4 9.0, J3-2
10.0, H3), 4.61-4.66 (2H, m, H1, H6, 2ꢀBnCH2), 4.73 (1H, d,
J 12.0, 2ꢀBnCH2), 4.91 (1H, d, J 12.0, 1ꢀBnCH2), 5.08 (1H, d,
NMR (CDCl3, 100.4 MHz) 13.98 (C11), 22.43, 25.05, 31.52 (C8,
C9, C10), 28.30 (C7), 37.32 (C3), 56.15 (C2), 58.76 (BnCH2),
96.45 (C5), 127.69-129.37 (Ar-C), 157.23 (C6); m/z (CI) MHþ
(C17H24NO) requires 258.1852, found 258.1848.
1-Benzyl-2-isopropyl-2,3-dihydropyridin-4-one (5h): νmax
(CHCl3, thin film) 2963 (C;H), 2237, 1698 (CdO), 1588,
1
1453 (C;N), 1407, 1360, 1263, 1201, 1095 cm-1; H NMR
(CDCl3, 400 MHz) 0.97 (3H, d, J 3.5, CH(CH3)2), 0.98 (3H, d,
J 3.0, CH(CH3)2), 2.29 (1H, m, H7), 2.69 (1H, dd, J3-2 3.0,
J
3-3 17.5, H3), 3.30 (1H, ddd, J2-3 3.0, J2-7 5.5, J2-3 8.0, H2),
J
9-10 8.0, H9), 7.10-7.34 (21H, m, 20ꢀAr-H, H10); 13C NMR
4.46 (1H, d, J 15.0, BnCH2), 4.54 (1H, d, J 15.0, BnCH2), 5.24
(1H, d, J5-6 7.0, H5), 7.30 (1H, d, J6-5 7.0, H6), 7.24-7.43
(5H, m, Ar-H); 13C NMR (CDCl3, 100.4 MHz) 17.91
(CH(CH3)2), 19.46 (CH(CH3)2), 29.16 (CH(CH3)2), 35.04
(C3), 59.17 (BnCH2), 61.19 (C2), 96.88 (C5), 127.42-129.27
(Ar-C), 156.77 (C6), 192.62 (C4); m/z (CI) MHþ (C15H19NO)
requires 230.1539, found 230.1533.
N-Phenyl methyl 2,3-di-O-acetyl-4-O-benzyl-6,7-dihydropyri-
din-8-one glucopyranoside (5i): [R]20D þ42.1 (c 1.1, CHCl3); νmax
(CHCl3, thin film) 2918 (C;H), 1748 (CdC), 1683 (CdO),
1653, 1574, 1493 (C;N), 1200, 1135 (C;O;C), 1051 (C-O)
cm-1; 1H NMR (CDCl3, 400.1 MHz) 1.88 (3H, s, COCH3), 2.02
(3H, s, COCH3), 2.63 (1H, dd, J7-6 2.5, J7-7 17.0, H7), 3.27 (1H,
t, J4-3 = J4-5 9.0, H4), 3.28 (1H, dd, J7-6 9.5, J7-7 17.0, H7),
3.33 (1H, dd, J4-5 7.5, J4-3 8.5, H4), 3.36 (3H, s, OCH3), 3.47
(1H, d, J 11.0, BnCH2), 3.84 (1H, dd, J5-6 2.5, J5-4 9.0, H5), 4.23
(1H, d, J 11.0 BnCH2), 4.69 (1H, app d, J 8.5, H6), 4.75 (1H, dd,
(CDCl3, 100.6 MHz) 40.2 (C7), 55.8 (OCH3), 56.3 (C6), 73.2
(BnCH2), 73.2 (BnCH2), 74.5 (C5), 75.7 (BnCH2), 77.7 (C4),
80.1 (C2), 82.8 (C3), 97.5 (C1), 100.8 (C9), 122.2-138.5 (Ar-C),
150.9 (C10), 191.1 (C8); m/z (CI) MHþ (C38H40O6N) requires
606.2856, found 606.2873.
N-Phenyl methyl 2,3,4-tri-O-benzyl-6,7-dihydropyridin-8-one
galactopyranose(5m): [R]20D -108.8 (c 0.9, CHCl3); νmax (CHCl3,
thin film) 2915 (C;H), 2366, 1641 (CdO), 1576, 1495 (C;N),
1346, 1200, 1124 (C;O;C), 1048 (C;O) cm-1 1H NMR
;
(CDCl3, 400.1 MHz) 1.97 (1H, app d, J7-7 17.5, H7), 2.71 (1H,
dd, J7-6 6.0, J7-7 17.5, H7), 3.21 (3H, s, OCH3), 3.97-4.04 (3H,
m, H4, BnCH2), 4.06 (1H, dd, J3-4 3.5, J3-2 10.0, H3), 4.35 (1H,
d, J5-6 10.0, H5), 4.46(1H, dd, J6-7 6.0, J6-5 10.0, H6), 4.59-4.71
(2H, m, H1, H2), 4.81-4.90 (2H, m, BnCH2), 5.09 (1H, d, J 11.5,
1ꢀBnCH2), 5.31 (1H, d, J9-10 7.5, H9), 7.25-7.37 (20H, m,
Ar-H), 7.42 (1H, d, J10-9 7.5, H10); 13C NMR (CDCl3, 100.6
MHz) 36.4 (C7), 55.2 (OCH3), 58.1 (C6), 65.4 (C5), 73.6 (C2),
73.7 (BnCH2), 74.4 (BnCH2), 76.2 (C3), 79.6 (C4), 98.6 (C1),
101.7 (C9), 120.1-138.5 (Ar-C), 148.9 (C10), 191.9 (C8); m/z
(CI) MHþ (C38H40NO6) requires 606.2850, found 606.2854.
N-Phenyl methyl 2,3,4-tri-O-benzyl-6,7-dihydropyridin-8-one
J
J
2-1 3.5, J2-3 10.5, H2), 4.83 (1H, d, J1-2 3.5, H1), 5.28 (1H, d,
9-10 7.5, H9), 5.43 (1H, dd, J3-4 9.0, J3-2 10.5, H3), 7.23-7.43
(6H, m, Ar-H, H10); 13C NMR (CDCl3, 100.6 MHz) 21.0
(COCH3), 21.1 (COCH3), 39.6 (C7), 56.1 (OCH3), 56.4 (C6),
71.1 (C2), 73.1 (C3), 73.3 (BnCH2), 74.6 (C5), 76.9 (C4), 96.7
(C1), 100.7 (C9), 123.0 (C10), 127.3-130.4 (Ar-C), 169.8
(COCH3), 170.1 (COCH3), 192.4 (C8); (MHþ 510.2122) found
510.2138, C28H32NO8 requires 510.2128.
mannopyranose (5n): [R]20 -2.1 (c 1.1, CHCl3); νmax (CHCl3,
D
thin film) 2916 (C;H), 1643 (CdO), 1584, 1493 (C;N), 1453,
1
1203, 1098 (C;O;C) cm-1; H NMR (CDCl3, 400.1 MHz)
2.57 (1H, d, J7-7 16.5, H7), 3.22 (1H, dd, J7-6 8.0, J7-7 16.5, H7),
3.27 (3H, s, OCH3), 3.64 (1H, t, J4-3=J4-5 10.0, H4), 3.71-3.74
(1H, m, H5), 3.80 (1H, dd, J3-2 3.0, J3-4 10.0, H3), 4.49-4.74
(9H, m, 3ꢀBnCH2, H1, H2, H6), 5.15 (1H, d, J9-10 7.5, H9),
7.13-7.38 (20H, m, Ar-H, H10); 13C NMR (CDCl3, 100.6
MHz) 40.36 (C7), 55.25 (OCH3), 57.62 (C6), 71.83 (BnCH2),
72.67 (BnCH2), 73.71 (BnCH2), 74.85 (C5), 74.97 (C4), 80.75
(C3), 98.50 (C1), 100.39 (C9), 122.83-129.68 (Ar-C), 151.77
(C10), 191.59 (C8); m/z (CI) MHþ (C38H40NO6) requires
606.2856, found 606.2855.
N-Phenyl methyl 2,3-di-O-acetyl-4-O-benzyl-6,7-dihydropyri-
din-8-one galactopyranoside (5j): [R]20D -109.0 (c 0.93, CHCl3);
νmax (CHCl3, thin film) 2929 (C;H), 1744 (CdC), 1642 (CdO),
1575, 1494 (C;N), 1370, 1223, 1140 (C;O;C), 1047 (C;O)
cm-1; 1H NMR (CDCl3, 400 MHz) 2.00 (1H, app d, J 17.0, H7),
2.08 (3H, s, COCH3), 2.11 (3H, s, COCH3), 2.73 (1H, dt, J7-6 =
J7-9 2.5, J7-7 17.0, H7), 3.20 (3H, s, OCH3), 3.99 (1H, app d,
J 2.5, H4), 4.46-4.49 (3H, m, H5, H6, 1ꢀBnCH2), 4.89 (1H, d,
J
1-2 3.0, H1), 4.96 (1H, d, J 11.5, 1ꢀBnCH2), 5.24 (1H, dd, J9-7
1.0, J9-10 7.5, H9), 5.35 (1H, dd, J2-1 3.0, J2-3 11.0, H2), 5.40
(1H, dd, J3-4 2.5, J3-2 11.0, H3), 7.26-7.37 (10H, m, Ar-H),
7.41 (1H, d, J10-9 7.5, H10); 13C NMR (CDCl3, 100.6 MHz) 20.9
(COCH3), 21.1 (COCH3), 37.2 (C7), 55.2 (OCH3), 57.7 (C6),
65.1 (C5), 68.9 (C2), 70.8 (C3), 74.4 (C4), 75.1 (BnCH2), 96.9
(C1), 102.8 (C9), 119.6-137.3 (Ar-C), 146.9 (C10), 169.8
(COCH3), 170.6 (COCH3), 190.6 (C8); m/z (CI) MHþ
(C28H32NO8) requires 510.2122, found 510.2128.
Methyl 2,3-di-O-acetyl-4-O-benzyl-6,7-dihydropyran-8-ol glu-
copyranoside (6i): νmax (NaCl disk/cm-1) 3520 m (OH), 3055 m
(C;H), 1753 s (CdO carbonyl ester stretch), 1665 m (CdC
stretch), 1135 s (R;O;Me, stretch), 1030 (C;O stretch);
[R]20 111.3 (c 0.2, CHCl3); δH (CDCl3, 250 MHz) 1.23-1.28
D
(1H, m, C(7a)H), 1.90-1.97 (1H, m, C(7b)H), 1.95 (3H, s, Me),
2.08 (3H, s, Me), 3.37 (3H, s, OMe), 3.60 (1H, dd J4,5 8.5, J5,6 9.0,
7216 J. Org. Chem. Vol. 75, No. 21, 2010

Burland et al.
JOCArticle
C(5)H), 3.76 (1H, dd, J3,4 7.0, J4,5 8.5, C(4)H), 4.44-4.54 (1H,
m, C(8)H), 4.59 (1H, ddd, J6,7 3.0, J6,7 8.0, J5,6 9.0, C(6)H), 4.76
(1H, d, J 10.0, ArCH2), 4.81 (1H, d, J 10.0, ArCH2), 4.81 (1H,
dd, J8,9 4.0, J9,10 6.0, C(9)H), 5.04 (1H, d, J1,2 3.5, C(1)H),
5.31-5.35 (2H, m, C(2)H, C(3)H), 6.41 (1H, d, J9,10 6.0, C(10)H),
7.23-7.37 (5H, m, ArH); δC (CDCl3, 100.0 MHz) 20.8 (Me),
20.9 (Me), 34.2 (C-7), 55.2 (OMe), 63.2 (C-8), 71.1 (C-2),
71.2 (ArCH2), 71.5 (C-5), 72.2 (C-6), 75.0 (C-3), 75.4 (C-4),
97.0 (C-1), 106.2 (C-9), 128.0-128.5 (Ar-C), 137.6 (iAr-C),
144.7 (C-10), 169.9-170.4 (RCOOR0); m/z (CI) 437 (MHþ,
35%), 393 (M - Ac, 34%); [C22H28O9]þ requires 437.1712, found
437.1708.
145.2 (C-10); m/z (CI) 533 (MHþ, 37%), 441 (M - OBn, 23%),
426 (22%); [C32H37O7] requires 533.2541, found 533.2534.
Methyl 2,3,4-tri-O-benzyl-6,7-dihydropyran-8-ol galactopyra-
noside (6m): νmax (NaCl disk/cm-1) 3530 br (OH stretching),
3365 m (C;H), 1665 m (CdC stretch), 1520 m (Ar, C;C
stretch), 1130 s (R;O;Me stretch); [R]20 22.2, 95.2 (c 0.5,
D
CHCl3); δH (CDCl3, 250 MHz) 1.80 (1H, ddd, J7a,8 5.0, J6,7a 7.5,
J7a,7b 10.0, C(7a)H), 2.43 (1H, ddd, J6,7b 3.0, J7b,8 7.0, J7a,7b 10.0,
C(7b)H), 3.26 (3H, s, OMe), 3.85 (1H, dd, J4,5 2.5, J5,6 10.0,
C(5)H), 3.96 (1H, dd, J2,3 3.0, J3,4 3.5, C(3)H), 4.04 (1H, dd, J2,3
3.0, J1,2 3.5, C(2)H), 4.05 (1H, ddd, J6,7b 3.0, J6,7a 7.5, J5,6 10.0,
C(6)H), 4.10 (1H, dd, J4,5 2.5, J3.4 3.5, C(4)H), 4.33 (1H, ddd,
J
8,9 2.0, J7a,8 5.0, J7b,8 7.0, C(8)H), 4.56 (1H, d, J 12.0, ArCH2),
Methyl 2,3-di-O-acetyl-4-O-benzyl-6,7-dihydropyran-8-ol ga-
lactopyranoside (6j). νmax (NaCl disk/cm-1) 3530 br (OH
stretch), 3065 m (C;H), 1740 s (CdO carbonyl ester stretch),
1665 m (CdC stretch), 1130 (R;O;Me stretch); [R]20D 136.2
(c 1.8, CHCl3); δH (CDCl3, 400 MHz) 1.61 (1H, dddd, J7a,10 1.0,
J6,7a 4.5, J7a,8 7.0, J7a,7b 11.0, C(7a)H), 1.91 (3H, s, Me), 2.01
(3H, s, Me), 2.51 (1H, ddd, J6,7b 7.0, J7b,8 7.5, J7b,7a 11.0,
C(7b)H), 3.30 (3H, s, OMe), 3.81 (1H, dd, J4,5 2.5, J5,6 9.5,
C(5)H), 4.17 (1H, ddd, J6,7a 4.5, J6,7b 7.0, J5,6 9.5, C(6)H),
4.20-4.23 (1H, m, C(4)H), 4.43 (1H, ddd, J8,9 2.0, J7a,8 7.0,
4.61 (1H, J 12.0, ArCH2), 4.66 (1H, d, J1,2 3.5, C(1)H), 4.77 (1H,
d, J 10.0, ArCH2), 4.81 (1H, d, J 10.0, ArCH2), 4.82-4.84 (1H,
m, C(9)H), 4.86 (1H, d, J 11.0, ArCH2), 4.89 (1H, d, J 12.0,
ArCH2), 6.16 (1H, d, J9,10 6.0, C(10)H), 7.19-7.35 (15H, m,
ArH); δC (CDCl3, 100.0 MHz) 34.8 (C-7), 55.6 (OMe), 62.7
(C-8), 69.3 (ArCH2), 70.5 (C-5), 71.5 (C-4), 72.4 (ArCH2), 73.4
(ArCH2), 73.9 (C-4), 75.7 (C-6), 76.4 (C-2), 79.2 (C-3), 79.2
(ArCH2), 99.2 (C-1), 106.5 (C-9), 127.7-128.6 (Ar-C),
138.8-139.0 (iAr-C), 144.5 (C-10); m/z (CI) 533 (MHþ,
41%), 441 (M - OBn, 15%), 426 (22%); [C32H37O7] requires
533.2541, found 533.2534.
Methyl 2,3-di-O-acetyl-4-O-benzyl-6,7-dihydropyran-8-ol
mannopyranoside (6n): νmax (NaCl disk/cm-1) 3560 br (OH),
3065 m (C-H), 1665 m (CdC stretch), 1525 m (Ar, C;C
stretch), 1130 s (R;O;Me stretch); [R]20D 22.2 (c 0.75, CHCl3);
δH (CDCl3, 250 MHz) 1.51-1.54 (1H, m, C(7a)H), 2.02 (1H,
ddd, J7b,8 7.0, J6,7b 7.5, J7a,7b 9.5, C(7b)H), 3.23 (3H, s, OMe),
3.48 (1H, dd, J1,2 3.0, J2,3 3.5, C(2)H), 3.71 (1H, dd, J5,6 6.0, J4,5
8.0, C(5)H), 3.76 (1H, dd, J4,5 8.0, J3,4 9.0, C(4)H), 4.12 (1H, dd,
J7b,8 7.5, C(8)H), 4.63 (1H, d, J 11.0, ArCH2), 4.69 (1H, d, J 11.0,
ArCH2), 4.82 (1H, dd, J8,9 2.0, J9,10 6.0, C(9)H), 4.99 (1H, d, J1,2
3.0, C(1)H), 5.27-5.33 (2H, m, C(2H), C(3)H), 6.29 (1H, dd,
J7a,10 1.0, J9,10 6.0, C(10)H), 7.22-7.28 (5H, m, ArH); δC
(CDCl3, 100.0 MHz) 21.2 (Me), 21.3 (Me), 34.7 (C-7), 55.7
(OMe), 62.5 (C-8), 69.2 (C-2), 70.7 (C-3), 71.2 (C-5), 71.5 (C-6),
74.7 (C-4), 75.7 (ArCH2), 97.6 (C-1), 106.7 (C-9), 128.2-128.7
(Ar-C), 138.3 (iAr-C), 144.4þ(C-10), 170.6 (RCOOR0), 170.8
(RCOOR0); m/z (CI) 437 (MH , 100%), 420 (M - OMe, 32%),
419 (42%); [C22H28O9]þ requires 437.1712, found 437.1720.
Methyl 2,3-di-O-acetyl-4-O-benzyl-6,7-dihydropyran-8-ol
mannopyranoside (6k). νmax (NaCl disk/cm-1) 3540 br (OH
stretch), 3055 m (C;H), 1750 s (CdO carbonyl ester stretch),
J2,3 3.5, J3,4 9.0, C(3)H), 4.21-4.27 (1H, m, C(6)H), 4.47 (1H, app
dt, J8,9 = J7a,8 3.5, J7b,8 7.0, C(8)H), 4.52-4.55 (1H, d, J 12.0,
ArCH2), 4.58 (1H, d, J 12.0, ArCH2), 4.63 (1H, d, J1,2 3.0,
C(1)H), 4.68 (1H, d, J 11.5, ArCH2), 4.70 (1H, d, J 11.5, ArCH2),
4.72 (1H, d, J 11.0, ArCH2), 4.76 (1H, d, J 11.0, ArCH2), 4.84
(1H, dd, J8,9 3.5, J9,10 6.0, C(9)H), 6.35 (1H, d, J9,10 6.0, C(10)H),
7.08-7.28 (15H, m, ArH); δC (CDCl3, 100.0 MHz) 34.5 (C-7),
55.0 (OMe), 63.7 (C-8), 71.7 (C-6), 72.3 (C-5), 72.9 (ArCH2), 73.3
(ArCH2), 73.7 (ArCH2), 74.3 (C-3), 75.5 (C-2), 80.6 (C-4), 99.8
(C-1), 105.6 (C-9), 127.7-12 8.6 (Ar-C), 138.5-138.7 (iAr-C),
145.8 (C-10); m/z (CI) 533 (MHþ, 42%), 441 (M - OBn, 21%),
349 (18%); [C32H37O7] requires 533.2541, found 533.2546.
1-Methoxy-7,8-benzylidene spiro[5.5]undex-9-en-8-one man-
nopyranoside (8a): νmax (NaCl disk/cm-1) 3071 m (C-H),
2860 m (aliphatic C;H stretch), 1689 s (CdO, ketone stretch),
1630 m (CdC stretch), 1143 s (R;O;CH3, stretch); [R]20D 91.1
(c 0.4, CHCl3); δH (CDCl3, 400 MHz) 1.71 (1H, dd J1,2a 4.5,
J2a,2b 15.0, C(2a)H), 2.25 (1H, dd, J7a,9 1.0, J7a,7b 16.5, C(7a)H),
2.63 (1H, d, J2a,2b 15.0, C(2b)H), 3.16 (1H, d, J7a,7b 16.5,
C(7b)H), 3.35 (3H, s, OMe), 3.53 (1H, d, J4,5 9.0, C(4)H), 3.75
(1H, ddd, J5,6b 3.0, J5,6a 8.0, J4,5 9.0, C(5)H), 4.34-4.39 (2H, m,
C(6)H), 4.74 (1H, d, J1,2a 4.5, C(1)H), 5.41 (1H, dd, J7,9 1.0, J9,10
6.0, C(9)H), 5.58 (1H, s, ArCH), 7.26-7.47 (6H, m, ArH,
C(10)H); δC (CDCl3, 100 MHz) 36.2 (C-7), 43.1 (C-2), 55.5
(OMe), 58.2 (C-5), 69.2 (C-6), 79.0 (C-3), 81.0 (C-4), 97.4 (C-1),
102.0 (ArCH), 106.0 (C-9), 126.1-129.1 (Ar-C), 137.0
(iAr-C), 161.6 (C-10), 191.3 (C-8; m/z (CI) 349 (MHþ, 34%),
318 (M- OMe, 54%), 305 (17%); [C19H25O6] requires 349.1653,
found 349.1646.
1660 m (CdC stretch), 1140 (R;O;CH3, stretch); [R]20
D
75.6 (c 0.80, CHCl3); δH (CDCl3, 250 MHz) 1.81-1.91 (1H,
m, C(7a)H), 2.00 (3H, s, Me), 2.01 (1H, ddd, J6,7b 7.0, J7b,8
7.5, J7a,7b 9.0, C(7b)H), 2.23 (3H, s, Me), 3.56 (1H, dd, J 2.0,
J 15.0, C(5)H), 3.97-4.01 (2H, m, C(6)H, C(4)H), 4.27 (1H,
app dd, J7b,8 7.5, J 10.0, C(8)H), 4.72 (1H, dd, J1,2 2.0, J2,3 2.5,
C(2)H), 4.77-4.79 (1H, m, C(9)H), 5.19 (1H, dd, J2,3 2.5, J3,4
8.0, C(3)H), 5.23 (1H, d, J1,2 2.0, C(1)H), 5.30 (1H, d, J 10.0,
ArCH2), 5.35 (1H, d, J 10.0, ArCH2), 6.37 (1H, dd, J 1.0, J9,10
6.5, C(10)H), 7.17-7.39 (5H, m, ArH); δC (CDCl3, 100.0
MHz) 20.9 (Me), 21.0 (Me), 30.1 (C-7), 55.1 (OMe), 63.5 (C-
8), 69.9 (C-5), 71.3 (C-6), 72.0 (C-3), 72.4 (ArCH2), 72.7 (C-6),
75.1 (C-2), 77.7 (C-4), 99.0 (C-1), 106.1 (C-9), 127.7-128.5
(Ar-C), 137.9 (iAr-C), 145.1 (þC-10), 169.9 (RCOOR0), 170.2
(RCOOR0); m/z (CI) 437 (MH , 22%), 393 (M - Ac, 32%),
351(26%); [C22H28O9]þ requires 437.1712, found 437.1718.
Methyl 2,3,4-tri-O-benzyl-6,7-dihydropyran-8-ol glucopyra-
noside (6l). νmax (NaCl disk/cm-1) 3530 br (OH), 3075 m
(C;H), 1673 m (CdC, stretch), 1140 s (R;O;CH3, stretch);
[R]20 11.4 (c 0.35, CHCl3); δH (CDCl3, 250 MHz) 1.39-1.49
D
(1H, m, C(7a)H), 1.96 (1H, ddd, J6,7a 7.0, J7b,8 8.0, J7a,7b 9.5,
C(7b)H), 3.29 (3H, s, OMe), 3.45-3.50 (2H, m, C(2)H, C(3)H),
3.65 (1H, app t, J3,4 = J4,5 8.5, C(4)H), 3.90 (1H, dd, J5,6 7.5, J4,5
8.5, C(5)H), 4.21 (1H, dd, J5,6 7.5, J6,7a 8.0, C(6)H), 4.40 (1H,
ddd, J7a,8 3.0, J8,9 3.5, J7b,8 8.0, C(8)H), 4.52 (1H, d, J 12.0,
ArCH2), 4.55 (1H, d, J 12.0, ArCH2), 4.57 (1H, d, J 11.0,
ArCH2), 4.63 (1H, d, J 11.0, ArCH2), 4.74 (1H, d, J 2.0, C(1)H),
4.78 (1H, d, J 10.0, ArCH2), 4.84 (1H, d, J 10.0, ArCH2), 4.92
(1H, d, J8,9 3.5, J9,10 6.5, C(9)H), 6.27 (1H, d, J9,10 6.5, C(10)H),
7.19-7.29 (15H, m, ArH); δC (CDCl3, 100.0 MHz) 34.9 (C-7),
55.5 (OMe), 63.6 (C-8), 71.5 (ArCH2), 71.9 (C-5), 73.7 (ArCH2),
75.5 (ArCH2), 76.0 (C-3), 77.1 (C-6), 79.8 (C-2), 82.5 (C-4), 98.7
(C-1), 106.2 (C-9), 127.9-128.7 (Ar-C), 138.3-138.9 (iAr-C),
Methyl 3-O-acetyl-4-oxy-6-O-benzyl-8-oxy-10-methoxyocta-
hydroisochromen-1-ol (8b): νmax (NaCl disk/cm-1) 3082 m
(C;H), 1752 s (CdO, carbonyl ester stretch), 1723 s (CdO,
ketone stretch), 1720 s (CdO, ketone stretch), 1121 s (R;O;
Me, stretch); [R]20 54 (c 0.4, CHCl3); δH (CDCl3, 400 MHz)
D
2.04 (3H, s, OMe), 2.47 (1H, app dt, J2,7a = J7a,9a 2.0, J7a,7b 15.5,
C(7a)H), 2.57 (1H, dd, J2,7b 7.5, J7a,7b 15.5, C(7b)H), 2.68 (1H,
J. Org. Chem. Vol. 75, No. 21, 2010 7217

Burland et al.
JOCArticle
app dt, J9a,10=J7a,9a 2.5, J9a,9b 15.0, C(9a)H), 2.82 (1H, dd,
J 1.0, J1,2 4.0, J1,2 4.5, J2,3 5.0, C(2)H), 5.47 (1H, dd, J7a,9 1.0, J9,10
6.0, C(9)H), 5.59 (1H, dd, J3,4 3.5, J2,3 5.0, C(3)H), 7.38 (1H, d,
9,10 6.0, C(10)H); δC (CDCl3, 62.8 MHz) 20.8 (Me), 21.0 (Me),
J9b,10 3.5, J9a,9b 15.0, C(9b)H), 3.13 (3H, s, OMe), 3.23 (1H, ddd,
2,7a 2.0, J1,2 4.0, J2,7b 7.5, C(2)H), 3.38 (3H, s, OMe), 3.75 (1H,
J
J
dd, J5,6a 6.5, J6a,6b 11.0, C(6a)H), 3.95 (1H, dd, J5,6b 3.0, J6a,6b
11.0, C(6b)H), 4.04 (1H, dd, J9a,10 2.5, J9b,10 3.5, C(10)H), 4.54
(2H, s, ArCH2), 4.75 (1H, d, J1,2 4.0, C(1)H), 4.95 (1H, dd, J5,6a
3.0, J5,6b 6.5, C(5)H), 7.16-7.54 (5H, m, ArH); δC (CDCl3, 100.0
MHz) 21.0 (Me), 38.7 (C-7), 41.9 (C-9), 42.2 (C-2), 56.0 (OMe),
58.4 (OMe0), 68.0 (C-6), 73.8 (ArCH2), 74.4 (C-5), 77.1 (C-3),
83.4 (C-10), 100.7 (C-1), 127.9-129.7 (Ar-C), 138.5 (iAr-C),
169.5 (RCOOR0), 202.8 (C-4), 207.1 (C-8); m/z (CI) 407 (MHþ,
100%), 375 (M - OMe, 65%), 342 (M - (OMe)2, 34%);
[C21H27O8]þ requires 407.1706, found 407.1712.
Methyl 2,3-di-O-acetate-4,5-ene-6,7-dihydropyran-8-one
mannopyranoside (8c). νmax (NaCl disk/cm-1) 3047m(C-Hing),
1759 s (CdO, carbonyl ester stretching), 1695 s (CdO carbonyl
stretching), 1630 m (CdC stretching), 1125 s (R;O;Me,
stretching); δH (CDCl3, 250 MHz) 2.06 (3H, s, Me), 2.12 (3H, s,
Me), 2.61 (1H, ddd, J7a,9 1.0, J6,7a 4.0, J7a,7b 16.5, C(7a)H), 2.85
39.1 (C-7), 39.3 (C-70), 56.5 (OMe), 56.7 (OMe), 63.4 (C-3), 65.2
(C-2), 65.5 (C-20), 77.7 (C-6), 98.1 (C-4), 98.5 (C-40), 98.8 (C-1),
98.9 (C-10), 107.4 (C-9), 107.5 (C-90), 149.0 (C-5), 149.1 (C-50),
162.3 (C-10), 162.4 (C-100), 170.0 (RCOOR0), 170þ.1 (RCOOR0),
191.1 (C-80), 191.2 (C-8); m/z (CI) 327 (MH , 44%), 296
(M - OMe, 100%), 258 (M - OAc, 34%); [C15H18O8]þ requires
327.1032, found 327.1040.
Acknowledgment. Financial support from MNL Pharma,
the School of Pharmacy (studentship to P.A.B.), and the
University of Reading (studentship to D.C.) is gratefully
ꢀ
acknowledged. We are also grateful to Dr Andre Cobb for
access to the microwave reactor and to Professor Laurence
Harwood for access to the high-pressure reactor.
0
(1H, dd, J6,7b 8.0, J7a,7b 13.5, C(7b)H), 2.89 (1H, dd, J 8.5, J6,7b
Supporting Information Available: Experimental proce-
dures as well as NMR spectra and characterization data. This
material is available free of charge via the Internet at http://
pubs.acs.org.
10.5, C(7b0)H), 3.51 (3H, s, OMe), 3.52 (3H, s, OMe), 4.84 (1H,
dt, J6,7a 3.5, J6,7b 13.5, C(6)H), 5.01 (1H, d, J1,2 4.0, C(1)H), 5.03
(1H, d, J1,2 C(10)H), 5.08 (1H, d, J3,4 3.0, C(4)H), 5.22 (1H, ddd,
7218 J. Org. Chem. Vol. 75, No. 21, 2010