Highly stereoselective synthesis of C-vinyl pyranosides via a Pd 0-mediated cycloetherification of 1-acetoxy-2,3-dideoxy-oct-2-enitols

Article abstract of DOI:10.1016/j.carres.2014.07.002

Oct-2-enitols undergo a Pd⁰-mediated cyclization to produce C-vinyl α-gluco- and α-galactopyranosides, and C-vinyl β-mannopyranoside in good yield and with high stereoselectivity. While substrate control demonstrates a clear stereochemical pref

Full text of DOI:10.1016/j.carres.2014.07.002

Carbohydrate Research 396 (2014) 43–47
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
Highly stereoselective synthesis of C-vinyl pyranosides
via a Pd0-mediated cycloetherification of 1-acetoxy-2,
3-dideoxy-oct-2-enitols
⇑
Ernest G. Nolen , Vivian C. Ezeh, Matthew J. Feeney
Colgate University, 13 Oak Drive, Hamilton, NY 13347, USA
a r t i c l e i n f o
a b s t r a c t
Oct-2-enitols undergo a Pd0-mediated cyclization to produce C-vinyl
a-gluco- and a-galactopyranosides,
Article history:
Received 6 June 2014
Received in revised form 2 July 2014
Accepted 3 July 2014
Available online 16 July 2014
and C-vinyl b-mannopyranoside in good yield and with high stereoselectivity. While substrate control
demonstrates a clear stereochemical preference during cyclization, the - and b-epimeric ratios are
enhanced by double diastereoselection using the (S,S) or (R,R)-DACH ligands.
a
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
C-Glycosides
C-Vinyl pyranosides
1,2-Dideoxy-hept-1-enitols
2,3-Dideoxy-oct-2-enitols
Cycloetherification
Pd0-mediated
The C-alkyl glycosides are useful for their enhanced stability
over the natural acetal-linked O-glycosides.1 These glyco-mimetics
are most often prepared from C-alkenyl pyranosides. In particular,
C-allyl and C-vinyl substrates serve as starting points in many syn-
thetic endeavors. Perhaps surprisingly, a literature search reveals
there are greater than five times more citations for C-allyl pyrano-
sides over C-vinyl pyranosides.2 To emphasize the disparity in
availability, one useful approach to a C-vinyl analogue is via the
Pd- or Ir-catalyzed alkene isomerization from a C-allyl substrate.3,4
Thus, the relative shortage of C-vinyl pyranosides served as the
impetus for our exploration of alternative synthetic schemes for
the production of these key starting materials.
low yields of predominantly b-C-vinyl glucosides and manno-
sides.18,19 As a variation of this last approach, Gervay-Hague
recently reported a route to
a-C-vinyl products by first equilibrat-
ing an
a
-galactosyl iodide to the beta-position.11 While most of
these routes transpire on fully protected glycosides, ring opening
of glycal epoxides affords C-vinyl glycosides with a free C-2 OH.
In these examples, the vinyl addition mediated by Al, Zn, and Zr
favor alpha gluco- and galactosides17,20–22 and Mg favors beta
products at lower temperatures.21,23
Our approach to C-vinyl glycosides enlists the Pd0-catalyzed
Tsuji–Trost allylation, which has been generally used for tetrahy-
dropyran syntheses.24–26 Parenthetically, Cossy has recently
reported similar cyclizations using the first-row metal Fe(III).27
Herein we describe a Pd0-catalytic method for the direct synthesis
of C-vinyl glucosides, galactosides, and mannosides using Pd0 itself
and in the presence of C2-asymmetric diaminocyclohexane diph-
enylphosphinobenzoic acid ligands (DACH).28 The retrosynthesis
of C-vinyl pyranosides (Scheme 1) thus requires the allylic ace-
tates, which are available by cross-metathesis between known
1,2-dideoxy-hept-1-enitols and 1,4-diacetoxybutene.
The C-vinyl pyranosides have found utility in the formation of
carbasugars5 and various C-linkages,6 including glycoconjugates
with amino acids,3,7–10 lipids,4,11 nucleoside phosphonates,12 and
other saccharides,13 for the production of compounds with immu-
nogenic, antiproliferative, and glycosidase inhibitory properties.
Strategies for C-vinyl pyranoside syntheses entail vinyl addition
to glucono and galactono-1,5-lactones followed by reduction with
Et3SiH and BF3ꢀEt2O to yield b-C-vinyl products;14–16 alkyne addi-
tion followed by controlled hydrogenation to afford an
a
-C-vinyl
Preparation of the precursors for the Pd0-catalyzed cyclization
required the formation of the 1,2-dideoxy-hept-1-enitols. The
galactoside;17,4 or vinyl addition to
a-halo glycosides to provide
D-gluco-hept-1-enitol 1a was readily available by a highly stereose-
lective divinylzinc addition to commercially available tri-O-benzyl
D
D
-arabinofuranose described by Nicotra.29 The
-manno-hept-1-enitols, 1b and 1c, were also reported by Nicotra
D-galacto- and
⇑
Corresponding author. Tel.: +1 315 228 7234.
E-mail address: enolen@colgate.edu (E.G. Nolen).
http://dx.doi.org/10.1016/j.carres.2014.07.002
0008-6215/Ó 2014 Elsevier Ltd. All rights reserved.

44
E. G. Nolen et al. / Carbohydrate Research 396 (2014) 43–47
by similar Grignard additions to pentoses, but we found the Wittig
methylenation30 of 3,4,6-tri-O-benzyl galactoside 2b31 and manno-
side 2c,32,33 to be more convenient (Scheme 2). Both 2b and 2c are
readily prepared in five steps with minimal chromatographic puri-
fication from their respective pentaacetates on a 30 g scale accord-
ing to the citations listed. The Wittig methylenation runs cleanly,
OBn
O
OBn
OH
R1
R2
R1
R2
BuLi, THF;
Ph3PCH3Br,
BuLi, THF
BnO
OH
BnO
R4
R3
R4
R3
1a
1b
1c
although the lower yield for the D-galacto-hept-1-enitol 1b is solely
(53%)
(78%)
2b
2c
due to difficulty in the separation of the triphenylphosphine
oxide byproduct. Extension to 1-acetoxy-oct-2-enitols was accom-
plished by cross-metathesis with 1,4-diacetoxybutene (5 equiv) in
refluxing dichloromethane using the second generation Grubbs
Ru-catalyst to give oct-2-enitols 3a–c in good yield.
OAc
OAc
a:
b
R
2 = OBn, R1,R3 = H, R4 =OH
: R1 = OBn; R2, R3 = H; R4 = OH
c: R2 = OBn, R1,R4 = H, R3 =OH
Grubbs
2nd gen
CH2Cl2
The final step in the synthesis of C-vinyl pyranosides involves
the Pd0-catalyzed cyclization of the oct-2-enitol compounds. Two
conditions were tested: cyclization utilizing approximately
0.15 mol equiv of Pd(PPh3)4 and triethylamine (Et3N) and an adap-
tation of the Tsuji–Trost allylation that required Pd2(dba)3 with a
C2 symmetric diphenylphosphinobenzoic acid (R,R-DACH or S,S-
DACH, also commonly abbreviated DPPBA). An attraction of these
chiral ligands is their availability in both enantiomeric forms to
explore double diastereoselection. In general, the oct-2-enitols
3a–c were mixed with the Pd0 catalyst in either THF or toluene
under anaerobic atmosphere and left to stir at rt for 24 h to furnish
high yields of C-vinyl pyranosides. The configurational assign-
ments at the pseudo-anomeric position correlated to the literature
OBn
OH
R4
R1
R2
3a
3b
3c
(83%)
(63%)
(82%)
BnO
OAc
R3
Scheme 2.
amplified the selectivity for the b-isomer, giving 6b exclusively.
Turning to the mismatched ligand chirality, the R,R-DACH with
Pd2(dba)3 afforded a reversal in selectivity for 4, albeit in a modest
1.0:3.5 (a:b) diastereomeric ratio. Under the same conditions the
galacto-octenitol 3b failed to react. Consequently, the S,S-DACH
spectral data for a- and b-C-vinyl D-glucopyranoside, at least to the
extent it has been revealed.6,20–23 Our 1H NMR data, including J1,2
coupling constants, COSY, and NOESY, confirmed the known
assignments and established the new C-glycosides reported herein,
switched the diastereomeric ratio for 6 giving 4.7:1.0 selectivity
for the
In summary, we have demonstrated the stereoselective synthe-
ses of C-vinyl -gluco- and -galactopyranosides, and C-vinyl b-
mannopyranoside using a Pd0-mediated cyclization. The
- and
b-epimeric ratios have been enhanced by double diastereoselec-
tion using the (S,S) or (R,R)-DACH ligands for the key cyclization.
This strategy nicely complements the glycal epoxide openings
and provides a unique entry to these C-vinyl pyranosides with a
free C-2 hydroxyl.
a-isomer.
namely the
-mannosides. In addition, the chemical shift of C-1 H was charac-
teristic depending on its conformational placement equatorial or
axial, so for all -C-vinyl products the equatorially positioned C-1
a-C-vinyl D-galactopyranoside and a- and b-C-vinyl
a
a
D
a
a
H was 0.5–0.7 ppm further downfield than its b-C-vinyl isomer
with an axially disposed C-1 H.
Cyclization of the oct-2-enitols using Pd(PPh3)4 showed a clear
substrate preference for
a or b isomers in each example (Scheme 3).
The ratios of isomers were determined by integrating the peaks
associated with the vinyl protons, one of which was clearly
resolved in each case. This cycloetherification showed good
substrate control of diastereoselectivity with greater than 10:1
1. Experimental
1.1. General methods
preference for the
4 and C-vinyl Gal 5. In contrast, the 6b-isomer was preferred 6:1
over the 6 -isomer for -manno-oct-2-enitol 3c cyclization. The
different C-2 configuration between Glc/Gal and Man appears to
play a role in orienting the Pd0 catalyst and subsequently deter-
mining the major product.
By introducing the chiral ligands, (R,R) and (S,S)-DACH with
Pd2(dba)3, we were able to observe matched double diastereoselec-
tion leading to greater selectivity in the cyclization, while mis-
matched cases led to a reversal of selectivity or no cyclization.
a-isomer over the b-isomer for the C-vinyl Glc
Chemicals were purchased from commercial sources and used
without further purification. All reactions were carried out under
an argon atmosphere using oven-dried glassware. Anhydrous
THF, toluene, and dichloromethane were obtained from activated
commercial columns. Thin-layer chromatography was performed
using commercially prepared 60-mesh silica gel plates and visual-
ization was achieved with UV light (254 nm) or a stain made from
mixing phosphomolybdic acid and cerium(IV) sulfate in sulfuric
acid. Silica gel (230–400) was used for flash column chromatogra-
phy. Optical rotations were recorded in CHCl3 using a 1.0 dm cell at
23 °C. All NMR spectral assignments were determined by 1H
(400 MHz), 13C (100 MHz) attached proton tests, COSY, HMQC
and NOESY 2D techniques in CDCl3. Peaks were referenced to resid-
ual chloroform signals (dH 7.26 ppm, or dC 77.0 ppm). Standard
abbreviations s, d, t, dd, br, app, and m refer to singlet, doublet,
triplet, doublet of doublets, broad, apparent, and multiplet, respec-
tively. High-resolution mass spectra were obtained from a Q-TOF
instrument by electron spray ionization (ESI) technique.
a
D
With the S,S-DACH, the selectivity for the
for the gluco- and galacto-substrates, giving solely the
(Table 1). For the manno-substrate, it was the R,R-DACH that
a-isomer was amplified
a
-isomer 5
a
BnO
BnO
BnO
BnO
O
OH
R1
R2
BnO
BnO
OAc
OH
OH
1.2. 1-Acetoxy-5,6,8-tri-O-benzyl-2,3-dideoxy-D-gluco-oct-2-
enitol (3a)
R1 = vinyl, R2 = H
R1 = H, R2 = vinyl
2,3-dideoxy-oct-2-enitols
To Grubbs second generation catalyst (130 mg, 0.152 mmol)
Scheme 1. Retrosynthesis for C-vinyl pyranosides.
under Ar was added a solution of 1a (695 mg, 1.53 mmol) and

E. G. Nolen et al. / Carbohydrate Research 396 (2014) 43–47
45
R1
137.5, 128.2, 128.2, 127.7, 124.8, 80.0, 77.4, 74.5, 74.4, 73.3, 71.2,
70.2, 69.3, 64.2, 20.8; HRMS: m/z calcd for C31H37O7: 521.2534
[M+H]+, found 521.2534.
R1
OBn
O
OBn
O
Pd(PPh3)4,
Et3N, tol
R2
BnO
3a
3b
R2
BnO
HO
HO
1.4. 1-Acetoxy-5,6,8-tri-O-benzyl-2,3-dideoxy-D-manno-oct-2-
enitol (3c)
4
α
5
α
4
90%
81%
(10:1)
(16:1)
β
5β
The diol 2c (2.05 g, 4.55 mmol) was dissolved in THF (35 mL),
and 1.6 M BuLi (5.3 mL, 8.6 mmol) was slowly added over 15 min
at ꢁ78 °C. The reaction was stirred and allowed to warm to rt over
1 h. In a separate flask, Ph3PCH3Br salt (9.6 g, 27 mmol) was sus-
pended in THF (68 mL), and 1.6 M BuLi (16.4 mL, 26.3 mmol) was
added at 0 °C. The suspension was stirred for 10 min at 0 °C, and
warmed to rt over 1 h. The 2c solution was slowly cannulated over
to the ylide suspension, heated to 45 °C, and stirred for 2.5 h. After
cooling to rt, it was quenched with acetone (10 mL) and stirred
overnight. The suspension was filtered, concentrated onto SiO2
gel, and chromatography using 20–30% EtOAc/Hex afforded 1c29
(1.58 g, 78%).
OH
Pd(PPh3)4,
Et3N, tol
BnO
BnO
BnO
OH
O
BnO
BnO
BnO
O
3c
6
α
6
β
75%
(1:6)
Scheme 3. Substrate control during cycloetherification.
1,4-diacetoxy-2-butene (1.2 mL, 7.6 mmol) in CH2Cl2 (3.0 mL). The
reaction was refluxed for 3 h, cooled, and stirred with 20 L 1:1
l
DMSO/ethyl vinyl ether for 30 min. The sample was concentrated
To Grubbs second generation catalyst (86 mg, 0.10 mmol) under
Ar was added a solution of 1c (455 mg, 1.02 mmol) and 1,4-diacet-
onto SiO2 gel and chromatography using 20–30% EtOAc/Hex affor-
a]
+5.5 (c 1.9, CHCl3); 1H NMR (400 MHz,
D
oxy-2-butene (817
lL, 5.08 mmol) in CH2Cl2 (2.0 mL). The reaction
ded 3a (661 mg, 83%). [
CDCl3): 7.46–7.25 (m, 14H), 5.94–5.75 (m, 2H), 4.75 (d,
was refluxed for 3 h, cooled, and stirred with 15
l
L 1:1 DMSO/ethyl
d
vinyl ether for 30 min. The sample was concentrated onto SiO2 gel
J = 11.4 Hz, 1H), 4.70–4.43 (m, 7H), 4.21–4.06 (m, 1H), 3.83–3.64
(m, 3H), 3.31 (s, 2H), 2.06 (s, 2H); 13C NMR (100 MHz, CDCl3): d
170.5, 137.8, 137.6, 137.6, 134.4, 128.2, 128.2, 128.2, 128.1,
127.8, 127.7, 127.6, 127.6, 125.0, 81.4, 78.5, 74.3, 73.5, 73.2, 70.8,
70.7, 70.5, 64.1, 20.7; HRMS: m/z calcd for C31H37O7: 521.2534
[M+H]+, found 521.2532.
and chromatography using 30% EtOAc/Hex afforded 3c (436 mg,
82%).
[
a]
D
+4.5 (c 2.0, CHCl3); 1H NMR (400 MHz, CDCl3):
d 7.43–7.25 (m, 15H), 5.96 (ddd, J = 17.2, 10.5, 5.2 Hz, 1H), 5.44
(dt, J = 17.2, 1.7 Hz, 1H), 5.26 (dt, J = 10.5, 1.6 Hz, 1H), 4.71 (d,
J = 11.3 Hz, 1H), 4.64–4.46 (m, 6H), 4.16–4.06 (m, 1H), 3.88 (dd,
J = 6.7, 3.0 Hz, 1H), 3.73–3.62 (m, 3H), 2.99 (d, J = 5.9 Hz, 1H), 2.92
(d, J = 6.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 170.6, 137.6,
137.5, 134.1, 128.3, 128.3, 128.2, 128.2, 128.1, 127.8, 125.5, 80.2,
78.1, 73.3, 73.2, 73.0, 70.9, 70.7, 69.9, 64.2, 20.7; HRMS: m/z calcd
for C31H37O7: 521.2534 [M+H]+, found 521.2533.
1.3. 1-Acetoxy-5,6,8-tri-O-benzyl-2,3-dideoxy-D-galacto-oct-2-
enitol (3b)
To 2b (2.05 g, 4.55 mmol) in THF (34 mL) was added 2 equiv of
2.5 M BuLi (3.46 mL, 8.65 mmol) at ꢁ78 °C over 15 min. The mix-
ture was stirred for 10 min and then allowed to warm to rt for
the next 1 h. In a separate flask, to triphenylphosphonium bromide
(4.88 g, 13.6 mmol) in THF (34 mL) was added BuLi (5.28 mL,
13.2 mmol) at ꢁ78 °C, stirred for 10 min, and then 1 h at rt. The
ylide solution was slowly cannulated into the 2b solution, forming
a cloudy orange mixture. The reaction was then heated to 45 °C for
2 h, then it was concentrated in vacuo, and chromatography with
20% EtOAc/Hex produced 1b29 (1.10 g, 53%).
1.5. General cyclization procedure of oct-2-enitols with
Pd(PPh3)4
To a solution of the appropriate oct-2-enitol in toluene (3 mL)
under Ar was added via cannula a yellow solution of 0.15 mol equiv
of Pd(PPh3)4 and Et3N (48 lL) in toluene (3 mL) giving rise to an
immediate dark brown color. The reaction was left to stir at rt
for 20 h and concentrated on SiO2. Chromatography with 15%
EtOAc/hexanes afforded the C-vinyl compounds as oils.
To Grubbs second generation catalyst (73 mg, 0.085 mmol)
under Ar was added a solution of 1b (384 mg, 0.856 mmol) and
1.6. (2
a,3S,4R,5R,6R)-4,5-Bis(benzyloxy)-6-((benzyloxy)methyl)-
1,4-diacetoxy-2-butene (410
The reaction was refluxed for 3 h, cooled, and stirred with 20
lL, 2.57 mmol) in CH2Cl2 (1.7 mL).
21
2-vinyltetrahydro-2H-pyran-3-ol (4
a)
lL
1:1 DMSO/ethyl vinyl ether for 30 min. The sample was concen-
trated onto SiO2 gel and chromatography using 20–30% EtOAc/
Compound 3a (119 mg, 0.229 mmol), Pd(PPh3)4 (31.8 mg,
0.0275 mmol) yielded 103 mg, 98% of [4
:4b] = [10:1]. 1H NMR
(400 MHz, CDCl3,
a
Hex afforded 3b as a solid (281 mg, 63%), mp 65–69 °C; [
a
]
ꢁ1.0
D
(c 2.0, CHCl3); 1H NMR (400 MHz, CDCl3): d 7.46–7.27 (m, 16H),
6.00–5.83 (m, 2H), 4.79–4.70 (m, 2H), 4.68–4.48 (m, 6H), 4.45 (d,
J = 4.6 Hz, 1H), 4.10 (s, 1H), 3.88–3.74 (m, 2H), 3.57 (ddd, J = 34.2,
9.4, 6.3 Hz, 2H), 2.73 (d, J = 9.0 Hz, 1H), 2.64 (d, J = 7.5 Hz, 1H),
2.06 (s, 3H); 13C NMR (100 MHz, CDCl3): d 170.6, 137.7, 137.5,
a
-isomer): d 7.40–7.24 (m, 15H, 3ꢂ PhH), 6.09
(ddd, J = 5.4, 10.8, 16.8 Hz, 1H, H-A), 5.47 (dt, J = 1.6, 17.5 Hz, 1H,
H-B0), 5.41 (dt, J = 1.6, 10.8 Hz, 1H, H-B00), 4.89–4.55 (m, 6H, 3ꢂ
CH2Ph), 4.52 (app t, J = 4.9 Hz, 1 H, H-1), 4.06 (q, J = 5.1 Hz, 1H,
H-5), 3.81 (m, 1H, H-2), 3.77–3.69 (m, 4H, H-3, H-4 and H-6a,b),
2.74 (d, J = 6.4 Hz, 1H, OH); 13C NMR (100 MHz, CDCl3,
a-isomer):
Table 1
d 138.1, 138.0, 137.6, 135.1, 132.9, 128.5, 128.4, 128.3, 127.9,
127.8, 127.6, 118.9, 80.7, 79.8, 78.8, 76.2, 74.1, 73.6, 73.6, 73.3,
Synthesis of C-vinyl pyranosides with and without asymmetric ligands
Oct-2-enitol
C-Vinyl pyranoglycosides 4–6, Yielda (%) [
a/b]
73.2, 70.6, 68.3; HRMS: m/z calcd for
C29H36NO5 478.2588
[M+NH4]+; found 478.2590.
Pd(PPh3)4
Pd2(dba)3 + R,R-DACH
Pd2(dba)3 + S,S-DACH
gluco 3a
galacto 3b
manno 3c
4 90 [10:1]
5 81 [16:1]
6 75 [1:6]
99 [1:3.5]
NR
55 [b only]
90 [31:1]
1.7. (2
a,3S,4R,5S,6R)-4,5-Bis(benzyloxy)-6-((benzyloxy)methyl)-
81 [
a only]
77 [4.7:1]
2-vinyltetrahydro-2H-pyran-3-ol (5
a)
a
Isolated yield after column chromatography primarily to filter out catalysts.
Compound 3b (128 mg, 0.246 mmol), Pd(PPh3)4 (35 mg,
0.031 mmol) yielded 92 mg, 81% of [5
:5b] = [16:1]. 1H NMR
Controls indicate that the diastereomeric ratio was not altered during
chromatography.
a

46
E. G. Nolen et al. / Carbohydrate Research 396 (2014) 43–47
(400 MHz, CDCl3,
a
-isomer): d 7.40–7.28 (m, 15H, 3ꢂ PhH), 6.03
1.13. (2b,3R,4R,5R,6R)-4,5-Bis(benzyloxy)-6-
((benzyloxy)methyl)-2-vinyltetrahydro-2H-pyran-3-ol (6b)
(ddd, J = 5.1, 10.9, 15.3 Hz, 1H, H-A), 5.50 (dt, J = 3.7, 17.6 Hz, 1H,
H-B0), 5.40 (dt, J = 3.7, 10.9 Hz, 1H, H-B00), 4.79 (dd, J = 11.6,
11.6 Hz, 2H, –CH2Ph), 4.64–4.51 (m, 5H, 2ꢂ CH2Ph and H-1), 4.24
(br m, 1H, H-2), 4.11 (m, 1H, H-5), 4.06 (t, J = 2.7 Hz, 1H, H-4),
3.80 (dd, J = 3.0, 6.7 Hz, 1H, H-6), 3.70 (dd, J = 4.0, 5.9 Hz,1H, H-
6), 3.63 (dd, J = 2.5 5.9 Hz, 1H, H-3), 2.28 (d, J = 3.2 Hz, 1H, OH);
Compound 3c (98 mg, 0.189 mmol), Pd2(dba)3ꢀCHCl3 (20.2 mg,
0.0155 mmol, 0.08 mol equiv), (R,R)-DACH (19.2 mg, 0.0278 mmol,
0.15 mol equiv). Yielded 48 mg, 55% of 6b. [a] + 1.0 (c 1, CHCl3);
D
other spectral data reported in Section 1.8.
13C NMR (100 MHz, CDCl3,
a-isomer): d 138.3, 138.1, 137.9,
131.9, 128.5, 128.4, 128.3, 127.9, 127.8, 127.7, 127.7, 127.7,
1.14. (2a,3R,4R,5R,6R)-4,5-Bis(benzyloxy)-6-
118.6, 79.1, 73.7, 73.5, 73.4, 72.2, 68.4, 67.9; HRMS: m/z calcd for
C
((benzyloxy)methyl)-2-vinyltetrahydro-2H-pyran-3-ol (6a)
29H36NO5 478.2588 [M+NH4]+, found 478.2584.
Compound 3c (102 mg, 0.197 mmol), Pd2(dba)3ꢀCHCl3 (16.9 mg,
0.0163 mmol, 0.08 mol equiv), (S,S)-DACH (23.5 mg, 0.0340 mmol,
1.8. (2b,3R,4R,5R,6R)-4,5-Bis(benzyloxy)-6-((benzyloxy)methyl)-
2-vinyltetrahydro-2H-pyran-3-ol (6b)
0.17 mol equiv). Yielded 70 mg, 77% of [6
(400 MHz, CDCl3, -isomer reported from the mixture): d 7.43–
a
:6b] = [4.7:1]. 1H NMR
a
Compound 3c (112 mg, 0.216 mmol), Pd(PPh3)4 (37.1 mg,
7.23 (m, 15H, 3ꢂ PhH), 5.88 (ddd, J = 5.3, 10.7, 15.9 Hz, 1H, H-A),
5.35 (dt, J = 1.5, 17.4 Hz, 1H, H-B0), 5.31 (dt, J = 1.4, 10.7 Hz, 1H,
H-B00), 4.74–4.51 (m, 7H, 3ꢂ CH2Ph and H-1), 4.06 (t, J = 3.1 Hz,
1H, H-2), 3.92–3.83 (m, 2H, H-4 and H-6a), 3.80–3.67 (m, 4H, H-
0.0321 mmol) yielded 74 mg, 75% of [6a
:6b] = [1:6]. 1H NMR
(400 MHz, CDCl3, b-isomer): d 7.43–7.20 (m, 15H, 3ꢂ PhH), 6.03
(ddd, J = 5.3, 10.7, 15.9 Hz, 1H, H-A), 5.48 (dt, J = 1.5, 17.4 Hz, 1H,
H-B0), 5.35 (dt, J = 1.4, 10.7 Hz, 1H, H-B00), 4.92–4.54 (m, 6H, 3ꢂ
CH2Ph), 4.06 (d, J = 2.6 Hz, 1H, H-2), 3.97 (dd, J = 1.2, 5.2 Hz, 1H,
H-1), 3.89 (t, J = 9.4 Hz, 1H, H-4), 3.78 (m, 2H, H-6a,b), 3.69 (dd,
J = 3.1, 9.1 Hz, 1H, H-3), 3.52 (ddd, 1H, H-5), 2.3 (s, 1H, OH); 13C
NMR (100 MHz, CDCl3, b-isomer): d 138.4, 138.3, 137.9, 134.6,
128.7, 128.5, 128.4, 128.2, 128.0, 127.9, 127.8, 127.7, 117.5, 83.3,
79.3, 78.6, 75.3, 74.5, 73.6, 71.7, 69.4, 69.2; HRMS: m/z calcd for
3, H-5 and H-6b), 2.63 (s, 1H, OH); 13C NMR (100 MHz, CDCl3,
a-
isomer): d 138.3, 138.2, 137.8, 134.0, 128.7, 128.5, 128.4, 128.2,
128.1, 128.0, 127.9, 127.8, 127.7, 118.6, 79.6, 76.4, 74.8, 74.6,
73.5, 73.4, 72.3, 69.4, 69.2; HRMS: m/z calcd for C29H36NO5
478.2588 [M+NH4]+, found 478.2590.
Acknowledgements
C
29H36NO5 478.2588 [M+NH4]+, found 478.2590.
The authors EGN and MJF express appreciation to the Jean Drey-
fus Boissevain program for their support.
1.9. General cyclization procedure of oct-2-enitols with
Pd2(dba)3ꢀCHCl3 and (R,R)-DACH or (S,S)-DACH
Supplementary data
A mixture of Pd2(dba)3ꢀCHCl3 and either (R,R) or (S,S) DACH
ligand was dissolved in THF (3 mL) to give a deep-red solution.
The solution was stirred for 30 min under a flow of Ar until the
color turned yellow. The activated catalyst was transferred via a
cannula to a solution of the appropriate oct-2-enitol in THF
(5 mL). The reaction was left to stir at rt for 24 h and concentrated
onto SiO2. Chromatography with 15% EtOAc/hexanes afforded the
C-vinyl compounds as oils.
Supplementary data (1H and 13C NMR data for all new pure
compounds 3a–c, 5a
, and 6b and 1H NMR data illustrating the dia-
stereomeric determinations for 4, 5, and 6) associated with this
article can be found, in the online version, at http://dx.doi.org/
10.1016/j.carres.2014.07.002.
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a,3S,4R,5R,6R)-4,5-Bis(benzyloxy)-6-
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D
other spectral data reported in Section 1.7.

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47
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