Functionalised bicyclic exo-glycals by alkynol cycloisomerisation of hydroxy 1,3-diynes and hydroxy haloalkynes

Helvetica Chimica Acta Vol. 88 (2005)

1885

Functionalised Bicyclic exo-Glycals by Alkynol Cycloisomerisation of

Hydroxy 1,3-Diynes and Hydroxy Haloalkynes

by Zhiwei Miao, Ming Xu, Barbara Hoffmann, Bruno Bernet, and Andrea Vasella*

Laboratorium f¸r Organische Chemie, ETH-Hˆnggerberg, HCI, CH-8093Z¸rich

Herrn Prof. Dr. Rolf Huisgen mit den besten W¸nschen herzlich zugeeignet.

Functionalised bicyclic exo-glycals are readily obtained by base-catalysed (typically MeONa in MeOH)

alkynol cycloisomerisation of ethynylated cyclic saccharides. Thus, base treatment of the phenylethynyl- and

halogenoethynylated 1-O-acetyl-ribofuranoses 22 24 and the 4-ethynylated 1-thioglucopyranosides 30 33

gave after deacetylation selectively the (Z)-configured exocyclic enol ethers 26 28 (84 91%) and 34 37

(63 76%), respectively, resulting from a trans-5-exo-dig cyclisation. The ring closure to the trans-dioxahex-

ahydroindans 34 37 is favoured by a concerted intramolecular protonation of the intermediate vinyl anion by

the neighbouring HOÀC(3). Cycloisomerisation of the 6-O-acetyl-4-(phenylethynyl)-1-thio-a-d-glucopyrano-

side 39 occurred via the corresponding phenylethynylated allenes to provide the galacto-configured (Z)- and

(E)-cis-dioxahexahydroindans 40 (30%) and 41 (51%). Surprisingly, the HOÀC(4) unprotected a-d-

galactopyranosyl-buta-1,3-diyne 15 and the b-d-glucopyranosyl-buta-1,3-diyne 51 (and its 2-bromoethynyl

analogue) undergo a 6-exo-dig ring closure to the 2,5-dioxabicyclo[2.2.2]octanes 16 19 and 52/53, respectively,

the ring closure requiring a boat conformation (B_1,4for 15, ^1,4B for 51). Ring strain (anti-reflex effect) prevents

an alkynol cycloisomerisation of 4-(phenylbuta-1,3-diynyl, bromoethynyl, or iodoethynyl)levoglucosan 56 59,

and 56 reacted by elimination to the hex-1-ene-3,5-diyne 59 (82%), while isomerisation of 57 and 58 led to

epimeric mixtures of the haloallenes 60 (82%) and 61 (68%).

Introduction.

exo-Glycals are versatile synthetic intermediates used for the

preparation of, e.g., ulosides [1 3], substituted endo-glycals, and functionalised C-

glycosides; their chemistry has recently been summarised by Taillefumier and Chapleur

[4]¹). Methods for the synthesis of exo-glycals comprise the Wittig-type olefination of

glyconolactones and glycosylphosphonium salts, the methylenation of glyconolactones

with Tebbe and Petasis reagent, addition elimination reaction, reductive elimination

of ketopyranosyl bromides, cyclisation of ethenylated alditols induced by electrophiles,

followed by elimination, and the Ramberg B‰cklund rearrangement of glycosyl

sulfones.

While alkynol cyclisation (cycloisomerisation) has been used as early as 1959 for

the structure elucidation of hydroxylated oligoacetylenes, as illustrated by the high-

yielding cyclisation of 1 to 2 [9][10] (Scheme 1), this facile cyclisation has, surprisingly,

not been used for the transformation of carbohydrates into exo-glycals, nor has the high

yielding base- or Ag -promoted cyclisation of hydroxylated haloalkynes and terminal

alkynes, such as 3 to 4 and 5 to 6 [11 14] found such an application²). Acceptor-

1

)

For more recent reports, see [5 8].

2

Alk-3-ynols and alk-4-ynols undergo a ready formal 5-endo-dig and 6-endo-dig cyclisation to endo-glycals

via transition-metal (Mo, Cr, W, Ru, Pd) vinylidene intermediates (see [15 17] and [18] for a recent

review). Sequential cyclisation and addition of alkynols to the resulting endo-glycals was used for the

preparation of oligosaccharides [16][19].

¹ 2005 Verlag Helvetica Chimica Acta AG, Z¸rich

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Helvetica Chimica Acta Vol. 88 (2005)

substituted acetylenes cyclise under basic conditions exclusively to 2-methylideneoxo-

lanes; a 1H-isochromene derivative was identified as an isomerisation product from the

corresponding 1-methylidene-1,3-dihydroisobenzofuran [20][21].

Scheme 1

In the context of the synthesis of acetylenosaccharides (see, e.g., [22 25] and [26]

for a recent review), we investigated the alkynol cycloisomerisation of buta-1,3-

diynylated and haloethynylated alcohols to exo-glycals, and report the results of the

cyclisation of glycofuranose- and glycopyranose-derived hydroxyacetylenes.

Results and Discussion.

To further evaluate the pronounced electrophilic

properties of buta-1,3-diynes and haloalkynes, we calculated the orbital energies of

acetylene (7), buta-1,3-diyne (9), the halogenated acetylenes 11 13, HCN (8), and

propiolonitrile (10) using the semi-empirical programs AM1 [27] and PM3[28])

implemented in the AMPAC 6.55 package [29]. The electrophilicity of these

compounds correlates with the energy and coefficients of the LUMO (Table 1).

According to both AM1 and PM3calculations, the LUMO energies of 8 13 are more

or less below the one of acetylene (7), except for the iodoacetylene 13, as calculated by

PM3(similar energy). The LUMO energy of buta-1,3-diyne ( 9) is markedly lower than

that of acetylene (7) and HCN (8) (AM1: DE(9/7) 1.375, DE(9/8) 1.047; PM3:

DE(9/7) 1.286, DE(9/8) 0.734 eV), evidencing a much higher electrophilicity. The

propiolonitrile (10) is even more electrophilic (AM1: DE(10/7) 1.809, DE(10/8)

1.481; PM3: DE(10/7) 1.862, DE(10/8) 1.310 eV). The LUMO energy of the

halogenated acetylenes 11 13 is higher than the one of buta-1,3-diyne (9), suggesting a

reduced electrophilicity. According to the AM1 calculation, the LUMO energy drops

from chloro- to bromo- and iodoacetylene, while PM3calculation led to an inverse

sequence. This difference is probably due to the decreasing accuracy in semi-empirical

calculations of atoms of the lower rows; the high LUMO energy resulting in the PM3

calculation of the iodide 13 suggests that the heavier atoms are less well implemented in

PM3than in AM1, and that iodoacetylene ( 13) and bromoacetylene (12) are better

acceptors for nucleophiles than chloroacetylene (11).

Helvetica Chimica Acta Vol. 88 (2005)

1887

Table 1. Energy and Coefficients of the LUMO of 7 13 Obtained by AM1 and PM3 Calculations

Energy [eV]

Coefficient at

atom 1

atom 2

atom 3atom 4

PM3 AM1 PM3

AM1

PM3AM1

PMA3 M1

7

8

9

10

11

12

13

2.0532.009

1.725

0.678

0.244

1.6631.713

1.447

À 0.71

À 0.73

À 0.57

À 0.61

À 0.71

À 0.72

À 0.71

0.71

0.69

0.71

0.69

1.457

0.723

0.147

À 0.72

À 0.56

À 0.60

À 0.71

À 0.72

À 0.71

0.430.43 0.43 0.43

À 0.57

À 0.49

À 0.56

À 0.51

0.47

0.69

0.68

0.46

0.69

0.40

À 0.15

À 0.14

À 0.11

0.42

À 0.17

À 0.10

À 0.11

1.763

2.025

1.412

Both AM1 and PM3calculations result in similar coefficients for the LUMO

orbitals of 7 13 (Table 1). The largest coefficient at C(1) of 9 13 predict that

nucleophilic attack is favoured at the unsubstituted acetylenic C-atom.

The regioselectivity of the addition of (hard) nucleophiles to acetylenes is also

influenced by the charge distribution. AM1 and PM3calculations led to similar net

atomic charges for 7 13 (Table 2). That 8 10 are more electrophilic than acetylene

(7) is predicted by the lower net atomic charge on C(1) of 8 10. A higher reactivity

towards hard nucleophiles of the buta-1,3-diyne (9) internal C-atoms is predicted on

the basis of their lower net atomic charge. The net atomic charges of propiolonitrile

(10) are in keeping with an expected attack of hard nucleophiles at the cyano C-atom.

The net atomic charge of C(1) decreases in the series chloro-, bromo-, to iodoacetylene

indicating the same relative reactivity as deduced from the LUMO energy values of the

AM1 calculation.

Table 2. Net Atomic Charges of 7 13 Obtained by AM1 and PM3 Calculations

Net atomic charge at

atom 1

AM1

atom 2

PM3AM1

atom 3atom 4

PM3 AM1

PM3AM1

PM3

7

8

9

10

11

12

13

À 0.22

À 0.19

À 0.17

À 0.10

À 0.18

À 0.14

À 0.12

À 0.19

À 0.16

À 0.15

À 0.08

À 0.16

À 0.12

À 0.14

À 0.22

À 0.05

À 0.06

À 0.10

À 0.21

À 0.32

À 0.40

À 0.19

À 0.07

À 0.05

À 0.08

À 0.32

À 0.30

À 0.34

À 0.06

À 0.02

0.16

À 0.05

0.00

0.28

À 0.17

À 0.01

À 0.15

À 0.04

0.22

0.23

0.29

0.28

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Helvetica Chimica Acta Vol. 88 (2005)

Alkynol Cycloisomerisation of a-d-Glucopyranosylbuta-1,3-diynes. Exploratory

experiments performed in 1995 to cyclise partially protected 4-buta-1,3-diynylated

glucopyranosides failed. However, treatment of the C₂-symmetric di(a-d-glucopyr-

anosyl)buta-1,3-diyne 15 obtained from 14 [30][31] with excess Na₂S ¥ 9 H₂O in boiling

MeOCH₂CH₂OH gave the ynenol ether 16 (60%, Entry 1 in Table 3), an exo-glycal,

and not the expected thiophene (Scheme 2). Similarly, benzylation of 15 with NaH and

BnBr in DMF at 08 gave a mixture of the perbenzylated exo-glycals 18 (53%) and 19

(21%). This result was rather surprising, considering that the alkynol cycloisomerisa-

tion of 15 requires a conformational change of the pyranosyl ring from a chair to a B_1,4

boat. Best yields of 16 (70%) were obtained with K₂CO₃albeit in a slower reaction

(24 h vs. 0.6 h; Entry 3); increasing the strength of the base lowered the yield of 19

(Entries 1 3).

Scheme 2

Table 3. Conditions and Yields in the Alkynol Cycloisomerisation of 15 and 16

Entry Starting Solvent

material

Base (8 10 equiv.) and reagent Conditions

Products and yields

1

2

3

4

5

6

7

8

15

16

MeOCH₂CH₂OH Na₂S ¥ 9 H₂O

MeOCH₂CH₂OH MeOCH₂CH₂ONa

MeOCH₂CH₂OH K₂CO₃

0.6 h at reflux 60% of 16

48 h at reflux 45% of 16

24 h at reflux 70% of 16

DMF

NaH, BnBr

3h at 0 8

53% of 18, 21% of 19

MeOCH₂CH₂OH Na₂S ¥ 9 H₂O

MeOCH₂CH₂OH MeOCH₂CH₂ONa

MeOCH₂CH₂OH K₂CO₃

0.6 h at reflux no reaction

48 h at reflux 10% of 17

24 h at reflux 37% of 17

DMF

NaH

3h at 0 8

no reaction

Helvetica Chimica Acta Vol. 88 (2005)

1889

While no product of double ring closure could be detected in the crude product of

15, we obtained the doubly ring-closed, C₂-symmetric dienol ether 17 by subjecting the

ynenol ether 16 to the same conditions as 15, although the yields of the second

cyclisation were distinctly lower (37% with K₂CO₃, 10% with MeOCH₂CH₂Na; Entries

7 and 6 in Table 3).

The enol ether moiety of 16 19 is evidenced by an IR band of medium strength at 1654 1662 cm^À1. The

¹H- and ¹³C-NMR spectra of 16, 18, and 19 evidence an a-d-glucopyranosylethynyl moiety (¹³C-NMR: 2 ss at

87.6 85.8 and at 84.6 83.5 ppm for C(10) and C(9), resp., 6 BnO groups in 16, and 7 BnO groups in 18 and 19).

HOÀC(14) of 16 resonates as d at 2.40 ppm, and J(14,OH) 1.7 Hz evidences an intramolecular H-bond to

BnOÀC(13), which is corroborated by the IR band at 3590 cm^À1(cf. [32][33]). The NMR spectra of 16 and 18

are very similar apart from the replacement of OH by OBn and reveal the same configuration. HÀC(8) of 16

and 18 resonates as a d at 4.64 4.66 ppm, whereas the d of HÀC(8) of 19 is shifted downfield to 5.15 ppm due to

the neighbouring OÀC(3), allowing to unambiguously assign the (E)-configuration to 19 and the (Z)-

configuration to 16 and 18. This assignment is confirmed by strong NOEs between HÀC(8) and HÀC(6) of 16

(8 14%). HÀC(8) of 16, 18, and 19 couples with HÀC(11) (J(8,11) 1.9 2.0 Hz), but not with HÀC(6).

These couplings evidence the 2,5-dioxabicyclo[2.2.2]octane skeleton of 16, 18, and 19 and a 6-exo-dig alkynol

cycloisomerisation of 15³). HÀC(6) of 19 is cis-oriented to the ethynyl group and, therefore, resonates

downfield as a broad d at 5.11 ppm (J(5,6) 3.6 Hz), whereas the signal of HÀC(6) of 18 appears upfield at

4.07 4.09 ppm. Due to virtual coupling [37] (HÀC(4) and HÀC(5) resonate as a narrow AB system at 3.91

3.88 ppm), HÀC(6) of 16 and 18 shows an additional splitting (16: J 3.5 and 1.9, 18: J 2.0 and 1.4 Hz). As it is

typical for enol ethers, the s of C(7) appears at low field (16/18: 159.6, 19: 161.8 ppm) and the d of C(8) at high

field (16/18: 83.4 83.6, 19: 85.35 ppm). The NMR spectra of 17 show a single set of signals and evidence the C₂-

symmetry. HÀC(8) resonates as s at 5.39 ppm (no allylic coupling). The upfield shift of the d of HÀC(6)

(4.14 ppm, J(5,6) 3.0 Hz) ascertains the (Z,Z)-configuration. The s of C(7) of 17 appears at 146.6 and the d of

C(8) at 97.9 ppm.

The formation of 2,5-dioxabicyclo[2.2.2]octanes in the alkynol cycloisomerisation

of 15 and 16 agrees well with the result of the semi-empirical calculation, i.e., an

enhanced electrophilicity at the terminal C-atoms of the buta-1,3-diyne moiety. The

lower yields of 17 than of 16 (see Table 3) evidence the decreased electrophilicity of the

alkynylated enol ether. The cycloisomerisation promoted by K₂CO₃, Na₂S ¥ 9 H₂O, and

MeOCH₂CH₂ONa led selectively to the (Z)-configured enol ethers 16 and 17, whereas

cyclisation of 15 promoted by NaH led to a ca. 7:3mixture ( Z)-18/(E)-19. NaH did not

promote the cyclisation of 16 (Entry 8 in Table 3). That a rather weak base in a protic

solvent and at higher temperature led to the best results of the cycloisomerisation

suggests that a fast chair boat interconversion, and particularly a concerted

protonation of the evolving linear trans-vinyl anion⁴) are favourable. Protonation of

a fully fledged vinyl anion as resulting from the NaH-promoted cyclisation results in a

mixture of the (E)- and (Z)-ynenol ethers 18 and 19.

3

)

A 7-endo-dig alkynol cycloisomerisation of 15 would lead to a 2,5-dioxabicyclo-[3.2.2]non-6-ene skeleton.

One expects a vicinal coupling J(6,7) of 6.6 Hz (MM3* modeling [34]) and the absence of a coupling

between HÀC(7) and HÀC(11); compare with corresponding values of

8 and 9.5 Hz of a

bicyclo[3.2.2]non-7-ene and a bicyclo[3.2.2]non-8-en-7-one, respectively [35][36].

4

)

As shown by AM1 calculations, deprotonation at C(1') of (E)- and (Z)-6-(but-2-ynylidene)-2,5-

dioxabicyclo[2.2.2]octane leads to the same almost linear (Z)-vinyl anion (CC^ÀÀC bond angle 1638,

OÀCC^ÀÀC dihedral angle À 0.28), whereas deprotonation of 6-methylidene-2,5-dioxabicyclo[2.2.2]oc-

tane gives two trihedral anions (CC^ÀÀH bond angles 122 1258). The (E) anion is favoured by an

anomeric effect. Treatment of 2-(but-2-ynyl)phenol with aqueous NaOH led indeed selectively to the (Z)-

configured enol ether [38].

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Helvetica Chimica Acta Vol. 88 (2005)

The successful alkynol cycloisomerisation of 15 prompted us to further investigate

such cyclisations of monosaccharides.

Alkynol Cycloisomerisation of d-ribo-Hex-5-ynofuranoses. The alkyne 20 was

prepared from d-ribose (22% overall yield) via a Corey Fuchs reaction [39].

Acetolysis of 20 (AcOH, Ac₂O, and conc. H₂SO₄) in THF at room temperature gave

81% of the b-d-configured acetate 21⁵) (Scheme 3). Sonogashira coupling between 21

and PhCꢀCBr yielded 81% of the butadiyne 22. Treatment of 21 with NBS and

catalytic amounts of AgNO₃[41] or with N-iodosuccinimide (NIS) and 1.5 equiv. of

AgNO₃[41][42] gave the bromide 23 (95%) and the iodide 24 (80%), respectively.

Chlorination of 21 with N-chlorosuccinimide (NCS) was sluggish. Treatment of 21

with 5.25% aqueous NaOCl [42] led to complete chlorination, but also cleaved the

anomeric AcO group. The intermediate hemiacetal cyclised in situ to the chloro-enol

ether 25 (90%). Deacetylation of 22 24 with MeONa in MeOH was accompanied by

cyclisation to the exo-glycals 26 (91%), 27 (84%), and 28 (91%), respectively. The

cyclisation of the halides 23 and 24 occurred at room temperature (overnight) and that

of the butadiyne 22 at 788 (4 h).

Scheme 3

a) Ac₂O, conc. H₂SO₄, AcOH/THF 1:1; 81%. b) (Bromoethynyl)benzene, [Pd₂(dba)₃], CuI, P(fur)₃, Et₃N,

DMF; 81% of 22. c) NBS, AgNO₃, acetone; 95% of 23. d) NIS, AgNO₃, NH₃/H₂O, acetone; 80% of 24.

e) NaOCl, H₂O; 90%. f) MeONa, MeOH; 91% of 26; 84% of 27; 91% of 28.

The ribo-hexofuranosides 21 28 show couplings of ca. 0 Hz for J(1,2) and J(3,4) (Table 4 in the Exper.

Part). This evidences an E_Oconformation also for the acetates 21 24 where the C(1) and C(4) substituents are

pseudoaxial. The enol ether moiety of 26 28 is evidenced by an IR band at 1692 1674 cm^À1. The s of the

5

)

For the use of an anomeric mixture containing 21, see [40].

Helvetica Chimica Acta Vol. 88 (2005)

1891

olefinic HÀC(6) resonates at 4.94 (26) and 5.82 5.83ppm ( 25, 27, and 28). The absence of coupling between

HÀC(6) and HÀC(4) agrees with a 3-methylidene-2,7-dioxabicyclo[2.2.1]heptane but not with a 2,8-

dioxabicyclo[3.2.1]oct-3-ene skeleton, where a vicinal coupling of ca. 6 Hz between the olefinic and bridgehead

H is expected. HÀC(4) of 25 28 resonates at 4.93 4.95 ppm at a similar position as H ÀC(4) of 21 24 (4.87

4.97 ppm); the absence of a downfield shift evidences the (Z)-configuration. The s of C(5) appears at 155.2 (26),

153.0 (28), 148.7 (27), and 146.8 ppm (25). As expected, C(6) resonates as a d at high field and the chemical shift

is strongly influenced by the substituent (88.6 ppm for the chloride 25, 80.1 ppm for the acetylene 26, 74.5 ppm

for the bromide 27, and 41.6 ppm for the iodide 28). The signals for the CꢀC group of 26 were assigned

according to [43], C(7) resonating at 82.61 and C(8) at 92.43 ppm.

The (Z)-configuration of 25 28 (dihedral angle OÀC(5)ÀC(6)ÀX (X C(7) or

halogen) ꢁÆ 1.08) was established by X-ray crystal-structure analysis. The unit cell of

26 28 contains a single molecule, whereas the unit cell of the chloride 25 contains two

slightly different molecules (Fig. 1)⁶). The analysis shows typical bond lengths and

bond angles, such as C(1)ÀOC(5) of 1.453 1.472 ä, C(5) ÀO of 1.366 1.397 ä,

C(5)C(6) of 1.307 1.328 ä, OÀC(5)C(6) of 124.1 125.98, and C(5)ÀC(6)ÀX

(X C(7) or halogen) of 122.3 127.8 8. The CÀHal bond lengths are 1.735 and 1.741 ä

(chloride 25), 1.869 ä (bromide 27), and 2.063ä (iodide 28). The CꢀC bond length of

26 is 1.199 ä, and a slight deviation of the acetylene group from linearity is indicated by

the bond angles C(6)ÀC(7)ꢀC(8) of 172.38 and C(7)ꢀC(8)ÀC(1') of 176.88. The p-

planes of the enol-ether moiety and the Ph group of 26 are orthogonal.

Fig. 1. Crystal structure of the 1-5-anhydro-d-ribo-hex-5-enofuranoses 25 28

6

)

The crystallographic data have been deposited with the Cambridge Crystallographic Data Centre as

deposition No. CCDC-248024 (26), CCDC-248027 (27), CCDC-248026 (28), CCDC-248025 (25), CCDC-

248028 (57), and CCDC-248029 (59). Copies of the data can be obtained, free of charge, on application to

the CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax. 44(1223)336033; e-mail: deposit@ccdc.

cam.ac.uk).

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Helvetica Chimica Acta Vol. 88 (2005)

The exclusive formation of 25 28 shows that a 5-exo-dig alkynol cycloisomerisa-

tion of d-ribo-hex-5-ynofuranoses is favoured, probably by proximity of the reacting

centers, although a 6-endo-dig cyclisation does not suffer from additional steric strain.

However, a 5-exo-dig alkynol cycloisomerisation of C(6)O unprotected 4-ethynyl-

glucopyranosides leading to trans-dioxahexahydroindans is sterically disfavoured. We

wondered whether such glucopyranosides would undergo a 6-endo-dig cyclisation to

trans-dioxadecalins.

Alkynol Cycloisomerisation of 4-Ethynyl-d-glucopyranosides. The buta-1,3-diyne

30 (82%), the bromide 32 (83%), and the iodide 33 (73%; Scheme 4) were prepared

from the 4-ethynyl-1-thio-b-d-glucopyranoside 29 [44], similarly as described for the

synthesis of 22 24. The chloride 31 was obtained in 64% yield by lithiation of 29 in

Scheme 4

a) (Bromoethynyl)benzene, [Pd₂(dba)₃], CuI, P(fur)₃, Et₃N, DMF; 82% of 30, 82% of 39. b) BuLi, then NCS,

THF; 64% of 31. c) NBS, AgNO₃, THF; 83% of 32. d) NIS, AgNO₃, NH₃/H₂O, acetone; 73% of 33. e) MeONa,

MeOH, reflux; 76% of 34, 63 % of 35, 74% of 36, 64% of 37, 30% of 40, and 51% of 41. f) Cu(OAc)₂, pyridine;

88%. g) NaOH, THF/MeOH/H₂O, 608; 99%. h) Na₂S ¥ 9 H₂O, 2-methoxyethanol; 20% of 44 and ca. 10% of an

unassigned 4 :3:2 mixture.

Helvetica Chimica Acta Vol. 88 (2005)

1893

THF with BuLi at À 788, followed by chlorination with NCS. Treatment of 30 33 with

MeONa in boiling MeOH for 4 h led to deacetylation and selective cyclisation of the

intermediate triols to the gluco-configured exocyclic enol ethers 34 37 (63 76%).

The buta-1,3-diyne 39 (82%) was obtained by Sonogashira coupling of 4-ethynyl-1-

thio-a-d-glucopyranoside 38 [30] and (bromo-ethynyl)benzene, while Eglinton cou-

pling of 38 yielded 88% of the C₂-symmetric acetylated buta-1,3-diyne 42 (Scheme 4).

MeONa in MeOH (4 h at reflux) transformed the acetate 39 into the corresponding

alcohol, which cyclised in situ to the galacto-configured (Z)- and (E)-ynenol ethers 40

(30%) and 41 (51%). Treatment of the diyne 42 with NaOH in THF/MeOH/H₂O for

15 min at 608 led in 99% yield to the diol 43. Boiling the diol 43 and Na₂S ¥ 9 H₂O in 2-

methoxyethanol for 30 min led to the gluco- and galacto-configured enol ether 44

(20%), and to a 4 :3:2 mixture of alkenes ( ca. 10%) that were not isolated⁷). Heating

43 in 2-methoxymethanol in the presence of excess K₂CO₃or treatment of 43 with NaH

in DMF at 08 did not afford 44.

The gluco-configuration of 30 37, 39, 42, 43, and of the directly alkynylated moiety of 44 is evidenced by

large J(3,4) and J(4,5) values (9.7 11.1 Hz), whereas the galacto-configuration of 40 and 41 is revealed by

distinctly smaller J(3,4) and J(4,5) values (3.4 7.0 Hz; see Tables 5 and 6 in the Exper. Part). In agreement with

the galacto-configuration, the olefinic HÀC(2') of 44 resonates as a br. s showing a w_1/2value of 8.7 Hz. The

trans-annulation of 34 37 is also evidenced by large J(5,6a) and J(5,6b) values (6.6 6.7 and 9.6 9.7 Hz, resp.)

whereas small J(5,6a) and J(5,6b) values (0 4.2 Hz) reveal the cis-annulation of 40, 41, and 44. Characteristic

geminal J(6a,6b) values (34 37: 7.8 8.0; 40, 41, and 44: 10.0 10.1 Hz) reflect the different orientation of both

HÀC(6) and the lone pairs at OÀC(6) (cf. [45]). The galacto-configuration of 40 and 41 was corroborated by

NOEs between HÀC(3) and HÀC(4) (7.5 12%; see Exper. Part).

The olefinic H-atom of the gluco-configured enol ethers 34 37 resonates as a d at 5.15 5.45 ppm (Table 5

in the Exper. Part). The chemical shift depends only weakly on the substituents and evidences that 34 37

possess the same configuration of the CC bond. J(4,CHC) of 2.1 2.4 Hz is compatible with an allylic

coupling of an exocyclic enol ether, but also with a vicinal coupling of an endocyclic enol ether (according to

MM3* calculation both couplings are 2.6 Hz). An endocyclic enol ether may, however, be excluded as it should

show similar J(5,6_eq), J(5,6_ax), and J(6_eq,6_ax) values as the corresponding 4,6-O-benzylidene acetal (typically 4.5,

10.5, and 10.5 Hz, resp.). The olefinic H-atom of the galacto-configured enol ethers 40 and 41 resonates as a d at

5.98 and 5.34 ppm, respectively (Table 6 in the Exper. Part). The large Dd value (0.64 ppm) is suggestive of an

(E)/(Z)-pair. Since the olefinic H-atom of both isomers is close to an O-atom ((Z)-isomer to BnOÀC(4); (E)-

isomer to OÀC(6)), the relative deshielding does not allow an unambiguous assignment of the configuration

although a comparison with the gluco analogue 34 suggests the (Z)-configuration for 40. Moreover, the coupling

of the olefinic H-atom with HÀC(4) (40: 2.2, 41: 1.9 Hz) and the small J(5,6_eq) and J(5,6_ax) values of 40 (0 and

2.2 Hz, resp.) do not allow to exclude the structure of an endocyclic enol ether. The structure of an exocyclic

enol ether is, however, evidenced by cross-peaks in the HMBC spectrum of 40 between HÀC(3) and the s at

164.23ppm, between H ÀC(5) and the s at 164.23ppm, and between H ÀC(2') and C(1)/C(2)/C(6) of the

PhCꢀC moiety. Similar cross-peaks are missing in the HMBC spectrum of 41, but here J(5,6_a) 3.1 and

J(5,6_b) 6.0 Hz exclude an endocyclic enol ether (according to MM3* calculation J(5,6_a) 1.0 and J(5,6_b)

3.0 Hz). The (Z)-configuration of 40 was evidenced by NOEs for HÀC(4) (2.6%) and HÀC(2) (2.4%)

observed upon irradiation of HÀC(2'). As expected, no NOE was observed upon irradiation of HÀC(2') of the

(E)-configured 41. In addition, the C(1') s of the enol ether moiety of 40 and 41 show the same relative shifts

(40: 164.2, 41: 168.6 ppm) as the (Z)- and (E)-lactone oximes and hydrazones (cf. [46 48]). HÀC(2') of the

dimer 44 resonates as a t at 5.31 ppm. It shows an allylic coupling with HÀC(4_Gal) and a homopropargylic

coupling with HÀC(4_Glc) (both 1.5 Hz). Signal overlap for HÀC(2), HÀC(3), HÀC(5), and H_aÀC(6) of the

galactose unit of 44 prevents an assignment of J(2,3), J(3,4), J(4,5), and J(5,6_a), while the similarity of

The ¹H-NMR spectrum of this mixture showed two signals at 5.18 and 5.14 ppm for olefinic H-atoms, and

7

)

two signals at 3.33 and 2.92 ppm for HÀC(4) of the glucopyranosyl residues.

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Helvetica Chimica Acta Vol. 88 (2005)

d(HÀC(2') and J(5,6_b) of the galactose unit of 44 and the corresponding values of 40 indicates the (Z)-

configuration.

4

The conformations of the pyranose ring of 40 and 41 differ. A flattened C₁is

evidenced for the (Z)-configured 40 by J(1,2) 4.8, J(2,3) 10.0, J(3,4) 5.6, and

4

J(4,5) 3.4 Hz (Table 6 in the Exper. Part). The C₁conformer of the (Z)-configured

41 is destabilised by a steric interaction between PhC ꢀ C and both BnO groups, and a

O

boat conformation is preferred. MM3* modeling of the S₂conformer of 41 predicts

vicinal coupling constants that are similar to the experimentally determined ones.

Only products of a formal 5-exo-dig alkynol cycloisomerisation of 30 33, 39, and

43 were observed. There is a striking difference between the b-d-glucopyranosides 30

33 affording only the gluco-configured (Z)-enol ethers and the a-d-glucopyranosides

39 and 43 affording a (E)/(Z) mixture of the galacto-configured enol ethers. We assume

that this difference results from a neighbouring group participation of HOÀC(3) and

not from the different anomeric configuration, cyclisation to a strained trans-

dioxahexahydroindan being favoured by concerted protonation of the evolving vinyl

anion by HOÀC(3) of the intermediate triols derived from 30 33. In the absence of

this intramolecular protonation, the alcohol derived from 39 (and similarly 43) may

equilibrate with the allenes A and further with the galacto isomer B (Scheme 4). The

allenes A may cyclise to the cis-dioxahexahydroindans 40 and 41 by an 5-exo-dig

processs, leading to an intermediate dihydrofuran that isomerises to the product by

migration of the double bond. Such a process appears more probable than a direct 5-

endo-dig cyclisation⁸)⁹). Alternatively, the galacto-configured buta-1,3-diyne B may

cyclise to the cis-dioxahexahydroindans 40 and 41. It is not clear why this cyclisation

with NaOMe in MeOH (concerted intermolecular protonation of the emerging vinyl

anion) leads preferentially to the sterically disfavoured 41, unless protonation leading

to 41 is (sterically?) favoured.

Alkynol Cycloisomerisation of b-d-Galactopyranosylethynes. The configuration at

C(1) and C(4) of the a-d-glucopyranosylethynes (Scheme 2) and of the b-d-

galactopyranosylethynes 49 51 (Scheme 5) differ, but the alkynyl and the hydroxy

substituents of all these compounds are cis-oriented. One expects that the galactopyr-

anosyl C-glycosides 49 51 will cyclise about as readily as the gluco-alkynols 14 and 15

and lead to epimeric 1,5-dioxabicyclo[2.2.2]octanes. The b-d-galactopyranosylethyne

49 was prepared from the diol 45 [63] by standard reactions. 4-Methoxybenzylation of

45 (!46), deallylation (!47), and Swern oxidation yielded the galactono-1,5-lactone

48 in 65% overall yield. The anomeric 1-ethynylated galactopyranoses were obtained

8

)

Treatment of allenic alcohols with various bases induces a 5-exo-dig cyclisation to endocyclic enol ethers

by attack on the central sp hybridised C-atom of the allenyl moiety [49 52]. However, treatment of (À)-

marasin, a buta-1,3-diynylated allenylethanol, with aqueous NaOH resulted in the formation of (Z)-2-

(penta-2,4-diynylidene)oxolane [53][54]. The protic and Lewis acid (silver salts or BF₃) catalysed 5-endo-

dig and 6-endo-dig cyclisation of a- and b-allenic alcohols to 2,5-dihydrofurans and 3,6-dihydro-2H-pyrans

have been described (see [55 57]). The HgO- or Pd(PPh₃)₄-catalysed allenol cycloisomerisation gave

endo- [58][59] and exocyclic enol ethers [60].

A 5-exo-dig cyclisation, followed by migration of the double bond, or a 5-endo-dig cyclisation appears

more probable than isomerisation to the corresponding triynol, followed by a 5-exo-dig cyclisation,

considering that distillation of pent-4-yn-1-ol (possessing an isolated, non-activated CꢀC bond) in the

presence of a catalytic amount of NaNH₂gave 2-methylideneoxolane [61][62].

9

)

Helvetica Chimica Acta Vol. 88 (2005)

1895

by treating 48 with lithium (trimethylsilyl)acetylide and reduced with Et₃SiH and BF₃¥

Et₂O. Under these conditions, the 4-methoxybenzyl ethers were also cleaved (compare

[64]) and the diol 49 was isolated in 63% yield. C-Desilylation (NaOMe in MeOH) to

50 and Sonogashira coupling with (bromoethynyl)benzene gave 85% of the buta-1,3-

diyne 51. Bromination of 50 with NBS and AgNO₃in THF at room temperature led to

the bromoacetylene which cyclised in situ to the enol ether 52 (93%). Cyclisation of 51

(NaOMe in MeOH) yielded 93% of the ynenol ether 53 which was acetylated to 54

(95%).

Scheme 5

a) PMBCl (4-methoxybenzyl chloride), NaH, DMF; 90%. b) [Ir(COD)(PPh₂Me)PF₆], H₂, THF, then I₂and

H₂O; 82%. c) DMSO/Ac₂O 2 :1; 88%. d) BuLi, Me₃SiCꢀCH, THF; Et₃SiH, BF₃¥ Et₂O, CH₂Cl₂/MeCN 1:1;

63%. e) MeONa, MeOH; 93%. f) (Bromoethynyl)benzene, [Pd₂(dba)₃], CuI, P(fur)₃, Et₃N, DMF; 85%. g) 50,

NBS, AgNO₃, THF; 93% of 52. h) 51, MeONa, MeOH; 93% of 53. i) Ac₂O, pyridine; 95%.

The b-d-configuration of the galactopyranosylethynes 49 51 is evidenced by J(1,2) 9.6 9.9 Hz (Table 7

in the Exper. Part). HOÀC(4) of 49 51 resonates as a dd at 2.64 2.70 ppm. In CDCl₃, the small J(4,OH)

1.5 2.0 Hz and the W-coupling with HÀC(5) (1.0 1.5 Hz) evidence an intramolecular H-bond of HOÀC(4) to

BnOÀC(3) (cf. [65]). J(6_b,OH) 7.2 8.4 Hz, and J(6_a,OH) 3.3 4.8 Hz of the diols 49 51 and the

monoalcohols 52 and 53 reveal an intramolecular H-bond of HOÀC(6) to OÀC(5). The enol ether moiety

of 52 54 is evidenced by an IR band at 1658 1664 cm^À1. The small coupling between the olefinic H-atom and

HÀC(1) of 52 54 (ꢁ1.0 Hz) reveals the dioxabicyclo[2.2.2]octane structure, and allows us to exclude a

dioxabicyclo[3.2.2]nonane structure (cf. Sect. 2.1). The upfield shift of HÀC(1) at 4.24 4.29 ppm evidences the

(Z)-configuration of 52 54, which is corroborated by NOEs of 9 14% between HÀC(1) and HÀC(2') of 53

(see Exper. Part).

As expected from the cyclisation of the a-d-gluco-analogues 15 and 16, a 6-exo-dig

alkynol cycloisomerisation of 51 and the corresponding bromoacetylene required the

conformational change from ⁴C₁to ^1,4B, and the bromoacetylene cyclised already under

the mild conditions of its preparation. No 2-methylidene-3,9-dioxabiyclo[3.3.2]nonane

resulting from a 6-exo-dig alkynol cycloisomerisation involving the primary OH group

4

1

and requiring a change of the ring conformation from C₁to C₄was found.

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Helvetica Chimica Acta Vol. 88 (2005)

Attempted Alkynol Cycloisomerisation of 4-Ethynylated Levoglucosans. We ex-

plored the limits of strain compatible with alkynol cyclisation by attempting to cyclise

the 4-ethynylated levoglucosan derivatives 56 58, which are easily accessible from the

known diol 55 [66] (Scheme 6). Due to the short CH₂O bridge in levoglucosans, the

distance between the axial substituents at C(2) and C(4) is considerably larger than the

typical distance between 1,3-diaxial substituents of cyclohexane (anti-reflex effect; see

[67] and refs. cit. therein). Thus, the O ¥¥¥ O distance between the 1,3-diaxial OH groups

is 3.299 ä in crystalline levoglucosan, but only 2.768 ä in crystalline 1,3,5-methylidyne-

myo-inositol [67]. A 5-endo-dig alkynol cycloisomerisation of 4-ethynylated levoglu-

cosans would lead to a severely strained anti-2,8,9-trioxatricyclo[4.2.1.1^2,5]decane¹⁰).

Scheme 6

a) (Bromoethynyl)benzene, [Pd₂(dba)₃], CuI, P(fur)₃, Et₃N, DMF; 76% of 56. b) NBS, AgNO₃, THF; 92% of

57. c) NIS, AgNO₃, NH₃, acetone/H₂O; 87% of 58. d) MeONa or t-BuOK, MeOH; 82% of 59, 62% of 60, 68%

of 61.

The solid-state structure of 57 was determined by X-ray analysis (Fig. 2)⁶). The

distance between OÀC(2) and C(1') is 3.196 ä. HOÀC(2) is involved in a intra-

molecular H-bond to OC(5) (OH ¥¥¥ OC(5) distance 2.395 ä, HÀC(2)ÀOÀH dihedral

angle À 159.68), whereas HOÀC(3) is engaged in an intermolecular H-bond to

OÀC(6). The ethynyl moiety does not act as additional H-acceptor of the

intermolecular H-bond revealed by the OH ¥¥¥ C(1') distance of 2.732 ä. It is slightly

bent, as indicated by the bond angles for C(4)ÀC(1')ÀC(2') and C(1')ÀC(2')ÀBr of

175.6 and 177.88, respectively.

Treatment of the buta-1,3-diyne 56 with MeONa in MeOH gave the diynenitol 59 in

82% yield. A similar treatment of the bromide 57 and the iodide 58 (with t-BuOK

instead of MeONa) led to a 9 :1 mixture of the epimeric bromoallenes 60 (82%) and to

a 1:1 mixture of the epimeric iodoallenes 61 (68%). As expected, no cyclisation

products could be found in the crude products obtained from 56 58.

In CDCl₃solution, HOÀC(2) of 56 58 is engaged in a bifurcated intramolecular H-bond to OÀC(5) and

the acetylene group as evidenced by J(2,OH) 11.8 11.9 Hz, and HOÀC(3) forms an intramolecular H-bond

to OÀC(6) (J(3,OH) 7.7 7.8 Hz ) . J(2,OH) of 59 11.2 Hz evidences in solution a bifurcated intramolecular

anti-2,8,9-Trioxatricyclo[4.2.1.1^2,5]decanes are not known. anti-2,8,9-Tricyclo[4.2.1.1^2,5]decane is 23.7 kcal/

10

)

mol higher in energy than the isomeric adamantane [68].

Helvetica Chimica Acta Vol. 88 (2005)

1897

Fig. 2. Crystal structure of the 4-ethynylated levoglucosans 57 and 59

H-bond to OÀC(5) and the CC bond. In the solid state of 59, however, HOÀC(2) is involved only in

intermolecular H-bonding (Fig. 2). J(2,OH) and J(3,OH) values of the allenes 60 and 61 are 8.2 8.7 and 6.8

7.1 Hz, and evidence intramolecular H-bonds to OÀC(5) and OÀC(6), respectively. The CCH group of 59 is

evidenced by the IR band at 1680 cm^À1, the downfield shift of HÀC(3) at 6.23 ppm, and the downfield shift of

C(3) (d at 133.5 ppm) and C(4) (s at 125.36 ppm). The allenyl moieties of 60 and 61 show the expected

spectroscopic characteristics (cf. [69]); i.e., an IR band at 1964 and 1955 cm^À1, a strong downfield shift of C(1') at

198.6 and 201.0 ppm, a weak upfield shift for C(4) at 108.6 and 102.1 ppm, and a strong upfield shift for C(2') at

73.1/73.2 and 39.0/38.3 ppm, respectively.

Conclusions.

Base-promoted alkynol cycloisomerisation of hydroxybuta-1,3-

diynes and haloalkynes occurs readily, and a 5- or a 6-exo-dig ring closure to exo-

methylidene-tetrahydofurans and -pyrans is preferred. If this ring closure is disfavoured

by ring strain, isomerisation to the isomeric allenes is preferred over an alkynol

cycloisomerisation. In keeping with earlier work on non-carbohydrate alkynols, our

results show that alkynol cycloisomerisation is favoured by cumulated triple bonds, a 1-

iodo 1-bromo, 1-chloro, 1-phenylchalcogeno (S or Se), or 1-(hetero)aryl substituent,

and the proximity of the reacting groups [11][12]. Alkynol cycloisomerisation promises

to become a useful additional route to (further functionalised) exo-glycals.

We thank Dr. B. Schweizer for the crystal-structure determination, C. J‰ger for the help in the synthesis of

the galacto-dimers, and the Swiss National Science Foundation and F. Hoffmann-La Roche AG, Basel, for

generous support.

Experimental Part

General. See [30].

1,1'-[Buta-1,3-diyne-1,4-diyl]bis[2,3,6-tri-O-benzyl-a-d-glucopyranosyl] (15). Under Ar,

a soln. of

Cu(OAc)₂(11.9 g, 65.7 mmol) in pyridine (110 ml) was heated to 608, stirred for 3h, treated with a soln. of

14 [30] (11.9 g, 65.7 mmol) in pyridine (10 ml), stirred for 1 h, and evaporated. Pyridine was removed by co-

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Helvetica Chimica Acta Vol. 88 (2005)

evaporation with toluene. FC (hexane/AcOEt 5 :1 ! 1 :1) gave 15 (1.24 g, 83%). R_f(hexane/AcOEt 3:1) 0.28.

[a]²_D⁵ 189.2 (c 1.0, CHCl₃). IR (CHCl₃): 3587m, 3510w, 3089w, 3066w, 2913m, 2871m, 2157w, 1603w, 1496m,

1454m, 1364m, 1330m, 1248m, 1069s, 1028s, 910w. ¹H-NMR (300 MHz, CDCl₃): 7.42 7.24 (m, 15 arom. H); 5.03

(d, J 11.4, PhCH); 4.81 (d, J 5.8, HÀC(1)); 4.78 (d, J 11.1), 4.73( d, J 12.0), 4.69 (d, J 12.0), 4.59 (d, J

12.3), 4.54 (d, J 12.0) (5 PhCH); 3.95 (br. dt, J ꢂ 9.6, 3.9, HÀC(5)); 3.79 (t, J 9.1, HÀC(3)); 3.73 (dd, J

10.5, 4.2, HÀC(6)); 3.69 (dd, J 10.5, 3.3, H'ÀC(6)); 3.615 (dd, J 9.3, 5.8, HÀC(2)); 3.62 (td, J 9.2, 2.3, addn.

of D₂O ! t, J 9.2, HÀC(4)); 2.44 (d, J 2.3, exchange with D₂O, HOÀC(4)). ¹³C-NMR (75 MHz, CDCl₃):

138.59, 137.74, 137.55 (3s); 128.50 127.66 (several d); 82.54 (d, C(3)); 78.52 (d, C(2)); 75.54, 73.72, 73.02 (3t, 3

PhCH₂); 74.81 (s, CꢀCÀC(1)); 73.15 (s, CꢀCÀC(1)); 73.89 (d, C(5)); 70.54 (d, C(4)); 69.44 (t, C(6)); 67.44 (d,

C(1)). HR-MALDI-MS: 937.391 ([M Na] , C₅₈H₅₈NaO₁₀; calc. 937.392).

(7Z)-2,6 :3,7 :11,15-Trianhydro-1,4,5,12,13,16-hexa-O-benzyl-8,9,10-trideoxy-d-erythro-l-ido-l-gulo-hexa-

dec-7-en-9-ynitol (16). a) A soln. of 15 (355 mg, 0.38 mmol) in MeOCH₂CH₂OH (10 ml) was treated with Na₂S ¥

9 H₂O (745.5 mg, 3.10 mmol), stirred for 40 min under reflux, cooled to 238, diluted with AcOEt (0.5 ml) and

hexane (0.8 ml), stirred for 30 min, and filtered through Celite. Evaporation of the filtrate and FC (hexane/

AcOEt 10 :1 ! 3:1) gave 16 (212 mg, 60%).

b) A soln. of 15 (20 mg, 22 mmol) in MeOCH₂CH₂OH (3ml) was treated with K ₂CO₃(24 mg, 0.17 mmol),

kept for 24 h at reflux, and evaporated. A soln. of the residue in AcOEt (10 ml) was washed with H₂O (5 ml),

dried (MgSO₄), and evaporated. FC (hexane/AcOEt 10 :1 ! 3:1) gave 16 (14 mg, 70%). R_f(hexane/AcOEt

3:1) 0.85. [ a]²_D⁵ 150.6 (c 1.0, CHCl₃). IR (CHCl₃): 3590w, 3066w, 2917m, 2870m, 2209w, 1661m, 1603w,

1496m, 1454m, 1335m, 1094s, 1027s, 909w. ¹H-NMR (500 MHz, CDCl₃, assignment based on a DQFCOSY.-

GRASP and a HSQC.GRASP spectrum): 7.38 7.22 (m, 30 arom. H); 4.98 (d, J 11.1, PhCH); 4.98 (dd, J 5.5,

2.0, HÀC(11)); 4.75 (d, J 11.4), 4.72 (d, J 11.9), 4.65 (d, J 11.8) (3PhC H); 4.66 (d, J 2.0, irrad. at 4.09 !

NOE of 14%, HÀC(8)); 4.59 (d, J 12.1), 4.45 (s, irrad. at 4.09 ! NOE of 5%, 2 H), 4.53( d, J 11.4, 2 H), 4.49

(d, J 11.9), 4.47 (d, J 11.6), 4.41 (d, J 11.9) (8 PhCH); 4.43 4.42 ( m, HÀC(3)); 4.38 (br. t, J ꢂ 6.5,

HÀC(2)); 4.09 (dd, J 3.5, 1.9, with virtual coupling, irrad. at 4.61 ! NOE of 8%, HÀC(6)); 4.01 (dt, J ꢂ 9.6,

3.9, HÀC(15)); 3.91 3.89 (m, irrad. at 4.09 ! NOE of 7%, HÀC(4), HÀC(5)); 3.82 (t, J 9.1, HÀC(13)); 3.73

(dd, J 10.7, 4.2, HÀC(16)); 3.68 (dd, J 10.6, 3.4, H'ÀC(16)); 3.65 (d, J 6.4, 2 HÀC(1)); 3.63 (dd, J 9.4, 5.6,

HÀC(12)); 3.61 (br. t, J 8.8, HÀC(14)); 2.40 (d, J 1.7, HOÀC(14)). ¹³C-NMR (75 MHz, CDCl₃, assignment

based on a HSQC.GRASP spectrum): 159.55 (s, C(7)); 138.92, 138.32, 137.06, 137.90, 137.52, 137.35 (6s);

128.32 127.47 (several d); 87.44 (s, C(10)); 83.56 (s, C(9)); 83.43 (d, C(8)); 82.20 (d, C(13)); 80.55, 79.53 (2d,

C(4), C(5)); 78.71 (d, C(12)); 75.41 (d, C(2)); 75.12, 73.37, 73.15, 72.28, 71.77, 71.43 (6t, 6 PhCH₂); 72.79 (d,

C(15)); 70.99 (d, C(3)); 70.64 (d, C(14)); 69.76 (t, C(1)); 69.52 (t, C(16)); 69.04 (d, C(6)); 67.27 (d, C(11)). HR-

MALDI-MS: 937.393 ([M Na] , C₅₈H₅₈NaO₁₀; calc. 937.392).

(7Z,9Z)-2,6 :3,7 :10,14 :11,15-Tetraanhydro-1,4,5,12,13,16-hexa-O-benzyl-8,9-dideoxy-d-erythro-l-ido-l-

gulo-hexadeca-7,9-dienitol (17). a) A soln. of 16 (27 mg, 29.5 mmol) in MeOCH₂CH₂OH (3ml) was treated with

K₂CO₃(40.7 mg, 0.29 mmol), kept for 48 h at reflux, and evaporated. A soln. of the residue in AcOEt (10 ml)

was washed with H₂O (8 ml), and the aq. layer was extracted with AcOEt (3 Â 10 ml). The combined org. layers

were washed with brine, dried (MgSO₄), and evaporated. FC (hexane/AcOEt 10 :1 ! 3:1) gave 17 (10 mg,

37%).

b) A soln. of 16 (20 mg, 21.9 mmol) in MeOCH₂CH₂OH (2 ml) was treated 1M MeOCH₂CH₂ONa in

MeOCH₂CH₂OH (200 ml, 0.22 mmol), kept for 70 h at reflux, and evaporated. A soln. of the residue in AcOEt

(10 ml) was washed with H₂O (8 ml), and the aq. layer was extracted with AcOEt (3x 10 ml). The combined

org. layers were washed with brine, dried (MgSO₄), and evaporated. FC (hexane/AcOEt 10 :1 ! 3:1) gave 17

(2 mg, 10%). R_f(hexane/AcOEt 3:1) 0.62. [ a]_D²⁵ 139.2 (c 0.5, CHCl₃). IR (CHCl₃): 3089w, 3066w, 2961m,

1

2869m, 1654m, 1604w, 1496m, 1454m, 1363m, 1324m, 1261s, 1101s, 1027s, 909w. H-NMR (300 MHz, CDCl₃):

7.39 7.23 (m, 15 arom. H); 5.39 (s, HÀC(8)); 4.60 (d, J 12.3), 4.55 (d, J 12.0), 4.51 (d, J 12.0), 4.50 (d, J

12.0), 4.49 (d, J 11.9), 4.41 (d, J 12.0) (6 PhCH); 4.41 4.34 (m, HÀC(2), HÀC(3)); 4.14 (d, J 3.0,

HÀC(6)); 3.92 3.86 (m, HÀC(4), HÀC(5)); 3.65 (d, J ꢂ 6.0, 2 HÀC(1)). ¹³C-NMR (75 MHz, CDCl₃): 146.59

(s, C(7)); 137.91, 137.63, 137.47 (3s); 128.33 127.56 (several d); 97.88 (d, C(8)); 81.17, 79.70 (2d, C(4), C(5));

75.93( d, C(2)); 73.21, 71.68, 71.17 (3t, 3 PhCH₂); 70.58 (d, C(3)); 70.05 (t, C(1)); 69.86 (d, C(6)). HR-MALDI-

MS: 937.391 ([M Na] , C₅₈H₅₈NaO₁₀; calc. 937.392).

Benzylation of 15. Under Ar, a soln. of 15 (737 mg, 0.80 mmol) in DMF (36 ml) was cooled to 08, treated

with 60% NaH in oil (270 mg, 8.0 mmol), stirred for 15 min, treated with BnBr (478 ml, 5.02 mmol), stirred for

3h, treated dropwise with MeOH (1.0 ml), and diluted with H ₂O (30 ml) and Et₂O (50 ml). After separation of

the layers, the aq. layer was extracted with Et₂O (2 Â 50 ml). The combined org. layers were washed with brine,

dried (MgSO₄), and evaporated. FC (hexane/Et₂O 10 :1 ! 5 :1) gave 18 (391 mg, 53%) and 19 (155 mg, 21%).

Helvetica Chimica Acta Vol. 88 (2005)

1899

Data of (Z)-2,6 :3,7:11,15-Trianhydro-1,4,5,12,13,14,16-hepta-O-benzyl-8,9,10-trideoxy-d-erythro-l-ido-l-

gulo-hexadeca-7-en-9-ynitol (18). R_f(hexane/AcOEt 3:1) 0.70. [ a]²_D⁵ 166.4 (c 0.5, CHCl₃). IR (CHCl₃):

3088w, 3066w, 2917m, 2867m, 2209w, 1662m, 1496m, 1454m, 1363m, 1089s, 1027s, 910w. ¹H-NMR (500 MHz,

CDCl₃; assignment based on a HSQC.GRASP spectrum): 7.38 7.21 (m, 33 arom. H); 7.14 7.13 (m, 2 arom. H);

4.98 (d, J 11.2, PhCH); 4.97 (dd, J 5.6, 2.0, HÀC(11)); 4.84 (d, J 10.6), 4.81 (d, J 10.9), 4.72 (d, J 11.9),

4.68 (d, J 11.9) (4 PhCH); 4.64 (d, J 2.0, HÀC(8)); 4.62 (d, J 12.1), 4.54 (s, 2 H), 4.51 (d, J 11.6), 4.48 (d,

J 11.0, 2 H), 4.47 (d, J 12.1), 4.45 (d, J 11.6), 4.41 (d, J 12.0) (9 PhCH); 4.43 4.42 ( m, HÀC(3)); 4.38

(br. t, J ꢂ 6.8, HÀC(2)); 4.07 (dd, J 2.0, 1.4, with virtual coupling, HÀC(6)); 4.04 (ddd, J 9.9, 3.3, 2.1,

HÀC(15)); 3.99 (t, J 9.2, HÀC(13)); 3.89 3.88 (m, HÀC(4), C(5)); 3.77 (dd, J 10.8, 3.5, HÀC(16)); 3.68

(dd, J 10.8, 2.0, H'ÀC(16)); 3.65 (dd, J 9.4, 5.5, HÀC(12)); 3.63 (d, J 6.7, 2 HÀC(1)); 3.61 (t, J 9.7,

HÀC(14)). ¹³C-NMR (75 MHz, CDCl₃; assignment based on a HSQC.GRASP spectrum): 159.57 (s, C(7));

138.92, 138.32, 138.12, 138.00, 137.89, 137.51, 137.35 (7s); 128.49 127.52 (several d); 87.64 (s, C(10)); 83.60 (s,

C(9)); 83.57 (d, C(8)); 83.09 (d, C(13)); 80.64, 79.63 (2d, C(4), C(5)); 79.25 (d, C(12)); 77.59 (d, C(14)); 75.60,

75.47, 75.13, 73.39, 72.57, 71.83, 71.48 (7t, 7 PhCH₂); 75.47 (d, C(2)); 73.20 (d, C(15)); 71.03( d, C(3)); 69.84 (t,

C(1)); 69.12 (d, C(6)); 68.62 (t, C(16)); 67.34 (d, C(11)). HR-MALDI-MS: 1027.442 ([M Na] , C₆₅H₆₄NaO₁₀

;

calc. 1027.445).

Data of (E)-2,6 :3,7:11,15-Trianhydro-1,4,5,12,13,14,16-hepta-O-benzyl-8,9,10-trideoxy-d-erythro-l-ido-l-

gulo-hexadeca-7-en-9-ynitol (19). R_f(hexane/AcOEt 3:1) 0.75. [ a]²_D⁵ 65.4 (c 0.5, CHCl₃). IR (CHCl₃):

3089w, 3066w, 2925m, 2868m, 2208w, 1654m, 1496m, 1454m, 1364m, 1090s, 1027s, 910w. ¹H-NMR (500 MHz,

CDCl₃, assignment based on a DQFCOSY.GRASP and a HSQC.GRASP spectrum): 7.32 7.19 (m, 33 arom.

H); 7.12 7.10 (m, 2 arom. H); 5.15 (d, J 1.9, HÀC(8)); 5.11 (br. d, J 3.6, HÀC(6)); 4.93( d, J 10.9, PhCH);

4.86 (dd, J 5.6, 1.9, HÀC(11)); 4.78 (d, J 10.8), 4.77 (d, J 10.9), 4.66 (d, J 11.4), 4.64 (d, J 11.4), 4.61 (d,

J 12.0), 4.53( d, J 12.1), 4.50 (d, J 11.9), 4.48 (s, 2 H), 4.48 (d, J 12.0), 4.43( d, J 11.6), 4.39 (d, J 12.2),

4.27 (d, J 11.3) (13 PhCH); 4.39 4.34 (m, HÀC(2), HÀC(3)); 3.93 3.91 (m, HÀC(15)); 3.91 (t, J 9.1,

HÀC(13)); 3.89 (t, J 3.5, irrad. at 5.11 ! d, J 3.5, HÀC(5)); 3.80 (dt, J 3.4, 1.6, irrad. at 4.36 ! d, J 3.4,

HÀC(4)); 3.67 (br. d, J 6.7, irrad. at 4.36 ! s, 2 HÀC(1)); 3.63 (dd, J 10.7, 3.5, HÀC(16)); 3.61 (t, J 9.8,

HÀC(14)); 3.60 (dd, J 9.4, 5.7, HÀC(12)); 3.48 (dd, J 10.7, 2.0, H'ÀC(16)). ¹³C-NMR (75 MHz, CDCl₃,

assignment based on a HSQC.GRASP spectrum): 161.76 (s, C(7)); 138.80, 138.30, 138.00, 137.90, 137.85, 137.40,

137.39 (7s); 128.56 127.53(several d); 85.86 (s, C(10)); 84.59 (s, C(9)); 85.35 (d, C(8)); 83.40 (d, C(14)); 80.42

(d, C(4)); 79.04 (d, C(12)); 78.73( d, C(5)); 77. 50 (d, C(14)); 75.66, 75.09, 73.48, 73.44, 73.29, 72.81, 71.77 (7t, 7

PhCH₂); 75.44 (d, C(2)); 73.48 (d, C(15)); 71.50 (d, C(3)); 69.97 (t, C(1)); 68.45 (t, C(16)); 67.44 (d, C(11)); 65.33

(d, C(6)). HR-MALDI-MS: 1027.438 ([M Na] , C₆₅H₆₄NaO₁₀; calc. 1027.445).

1-O-Acetyl-5,6-dideoxy-2,3-O-isopropylidene-b-d-ribo-hex-5-ynofuranose (21). A suspension of 20 [39]

(500 mg, 2.5 mmol) in THF (5 ml) was treated with AcOH (5 ml) and Ac₂O (1.4 g, 13.9 mmol), cooled to 58,

stirred for 0.5 h, treated dropwise with conc. H₂SO₄(0.25 ml) over a period of 5 min, and stirred at 238 for 12 h.

The mixture was poured on ice (20 g), stirred for 1 h, and extracted with AcOEt (3 Â 20 ml). The combined org.

fractions were washed with sat. NaHCO₃soln. (20 ml), H₂O (20 ml) and brine (20 ml), dried (MgSO₄), and

evaporated. FC (hexane/Et₂O 2 :1) gave 21 (460 mg, 81%). White solid. R_f(hexane/Et₂O 1 :1) 0.63. M.p. 75

768. [a]²_D⁵ À102.3( c 1.0, CHCl₃). IR (CHCl₃): 3307m, 3029w, 2995w, 2943w, 2124w, 1746s, 1602w, 1458w,

1430w, 1376s, 1228s, 1204m, 1159m, 1104s, 1058m, 1015s, 971s, 922w, 864s. ¹H-NMR (300 MHz, CDCl₃): see

Table 4; additionally, 2.01 (s, AcO). ¹³C-NMR (75 MHz, CDCl₃): see Table 4; additionally, 169.19 (s, CO);

21.08 (q, Me). ESI-MS: 211 ([M À Me] ). Anal. calc. for C₁₁H₁₄O₅(226.23): C 58.40, H 6.24; found: C 58.24, H

6.21.

1-O-Acetyl-5,6,7,8-tetradeoxy-2,3-O-isopropylidene-8-C-phenyl-b-d-ribo-octa-5,7-diynofuranose (22). A

suspension of [Pd₂(dba)₃] (15.7 mg, 0.0339 mmol), CuI (5.26 mg, 0.0274 mmol), P(fur)₃(16 mg, 0.068 mmol),

21 (310 mg, 1.37 mmol), and (bromoethynyl)benzene (250 mg, 1.37 mmol) in DMF (5 ml) was degassed twice

and stirred at 228 for 5 min. The mixture was treated with Et₃N (0.7 ml) and stirred for 12 h at 228. The soln. was

diluted with Et₂O (20 ml), and treated with H₂O (20 ml) and 0.1m aq. HCl (5.5 ml). The org. layer was washed

with H₂O (2 Â 15 ml), and the aq. layer was extracted with Et₂O (4 Â 15 ml). The combined org. fractions were

dried (MgSO₄) and evaporated. FC (hexane/AcOEt 4 :1) gave 22 (360 mg, 81%). Pale yellow solid. R_f(hexane/

AcOEt 2 :1) 0.56. M.p. 86 878. [a]²_D⁵ À112.1 (c 1.0, CHCl₃). IR (CHCl₃): 3030w, 3014w, 2981w, 2246w, 1747s,

1491w, 1443w, 1384m, 1376m, 1227s, 1204m, 1159m, 1101s, 1054s, 1014m, 971s, 877w, 861w. ¹H-NMR (300 MHz,

CDCl₃): see Table 4; additionally, 7.50 7.25 (m, 5 arom. H); 2.13( s, AcO). ¹³C-NMR (75 MHz, CDCl₃): see

Table 4; additionally, 169.36 (s, CO); 132.52 (2d); 129.48 (d); 128.40 (2d); 121.05 (s); 21.22 (q, Me). MALDI-

MS: 349 ([M Na] ). HR-MALDI-MS: 349.1045 ([M Na] , C₁₉H₁₈NaO₅; calc. 349.1046). Anal. calc. for

C₁₉H₁₈O₅(326.35): C 69.93, H 5.56; found: C 70.08, H 5.57.

1900

Helvetica Chimica Acta Vol. 88 (2005)

Table 4. Selected ¹H- and ¹³C-NMR Chemical Shifts [ppm], and Coupling Constants [Hz] of the Unsaturated d-ribo-

Hexofuranoses 21 28 in CDCl₃

21

22

23

6.20

4.934.934.54

4.81

4.87

24

26^a)

25

5.34

27

5.28

28

HÀC(1) 6.21

HÀC(2) 4.94

HÀC(3) 4.82

HÀC(4) 4.88

HÀC(6) 2.55^b)

6.24

4.99

4.84

6.20

5.86

5.07

4.41

4.50

4.51

4.81

4.97

4.44

4.95

4.94

1.47, 1.32

0

4.41

4.934.934.95

5.82

1.46, 1.31

0

5.4

0

4.41

4.995

5.82

1.46, 1.31

0

5.4

5.83

1.45, 1.30

0

5.7

Me₂C

J(1,2)

J(2,3)

J(3

1.47, 1.33

1.48, 1.34

1.46, 1.32

0

5.4

0

1.45, 1.31

0

6.0

5.4

0

5.7

0

5.4

0

,4)

0

C(1)

C(2)

C(3)

C(4)

C(5)

C(6)

C(7)

C(8)

Me₂C

102.16

85.21

84.99

75.92

80.64

75.24

101.96

85.07

84.99

76.55

79.67

71.82

72.78

78.63

113.54

102.03101.98

84.98

84.94

76.76

77.2391.13155.21

.12 103 102.89

102.95

80.67

79.45

78.17

102.83

80.71

80.06

77.99

152.97

74.5341.57

85.18

84.94

77.30

80.62

78.06

78.93

80.74

80.23

77.88

146.79

148.70

48.01

5.12

80.09

82.61

88.58

92.43

113.42

113.37

113.45

114.08

113.94

114.02

114.04

26.40, 25.18 26.42, 25.25 26.39, 25.19 26.38, 25.19 25.99, 25.63 25.92, 25.55 25.96, 25.60 25.92, 25.57

^a) Assignment based on a DQFCOSY and a HSQC spectrum, and on a NOE (2.5%) observed for HÀC(2)

b

upon irradiation of HÀC(1). ) ⁴J(4,6) 2.4 Hz.

1-O-Acetyl-6-C-bromo-5,6-dideoxy-2,3-O-isopropylidene-b-d-ribo-hex-5-ynofuranose (23). A suspension

of 21 (56 mg, 0.25 mmol) and NBS (60 mg, 0.336 mmol) in acetone (3 ml) was treated with AgNO₃(6 mg,

0.036 mmol) and stirred for 30 min at 228. After evaporation, the residue was partitioned between H₂O and

AcOEt. The aq. layer was extracted with AcOEt (3 Â 15 ml). The combined org. fractions were washed with

brine (10 ml), dried (MgSO₄), and evaporated. FC (hexane/AcOEt 4 :1) gave 23 (71 mg, 95%). White solid. R_f

(hexane/AcOEt 4 :1) 0.43. M.p. 63 648. [a]_D²⁵ À76.8 (c 1.0, CHCl₃). IR (CHCl₃): 3027w, 3015m, 2218w,

1746s, 1376m, 1313w, 1159m, 1100s, 1055m, 1014m, 971s, 927w, 865m. ¹H-NMR (300 MHz, CDCl₃): see Table 4;

additionally, 2.08 (s, AcO). ¹³C-NMR (75 MHz, CDCl₃): see Table 4; additionally, 169.30 (s, CO); 21.17 (q,

Me). HR-EI-MS: 290.9689 (97, [M À Me] , C₁₀H₁₀⁸¹BrO₅, calc. 290.9691), 288.9715 (100, [M

Me] ,

C₁₀H₁₀⁷⁹BrO₅; calc. 288.9712). Anal. calc. for C₁₁H₁₃BrO₅(305.12): C 43.30, H 4.29; found: C 43.08, H 4.13.

1-O-Acetyl-5,6-dideoxy-6-C-iodo-2,3-O-isopropylidene-b-d-ribo-hex-5-ynofuranose (24). A suspension of

21 (56 mg, 0.25 mmol) in acetone (3ml) was added dropwise to a stirred soln. of AgNO ₃(65 mg, 0.38 mmol) and

diluted NH₃/H₂O (1 drop) in H₂O (3ml). The mixture was stirred for 5 min at 22 8, treated with NIS (90 mg,

0.4 mmol), and stirred for 30 min (the mixture became homogeneous after ca. 5 min and then turbid again).

After evaporation, the residue was partitioned between H₂O and AcOEt. The aq. layer was extracted with

AcOEt (3 Â 15 ml). The combined org. layers were washed with brine (10 ml), dried (MgSO₄), and evaporated.

FC (hexane/AcOEt 4 :1) gave 24 (70 mg, 80%). White solid. R_f(hexane/AcOEt 4 :1) 0.52. M.p. 59 608. [a]_D²⁵

À60.8 (c 1.0, CHCl₃). IR (CHCl₃): 3027m, 3015w, 2929m, 2852m, 2190w, 1733s, 1602w, 1246s, 1159w, 1100m,

1

1046m, 1013m, 971m, 864m. H-NMR (300 MHz, CDCl₃): see Table 4; additionally, 2.08 (s, AcO). ¹³C-NMR

(75 MHz, CDCl₃): see Table 4; additionally, 169.33 (s, CO); 21.23( q, Me). HR-EI-MS: 337.9612 (11, [M À

Me] , C₁₀H₁₀¹²⁸IO₅; calc. 337.9607), 336.9577 (100, [M À Me] , C₁₀H₁₀¹²⁶IO₅; calc. 336.9573). Anal. calc. for

C₁₁H₁₃IO₅(352.13): C 37.52, H 3.72; found: C 37.55, H 3.79.

(Z)-1,5-Anhydro-6-C-chloro-6-deoxy-2,3-O-isopropylidene-b-d-ribo-hex-5-enofuranose (25). A suspen-

sion of 21 (240 mg, 1.06 mmol) in 5.25% aq. NaOCl (35 ml) was stirred at 228 for 16 h (the mixture became

homogeneous within 30 min), diluted with H₂O (10 ml), and extracted with AcOEt (3 Â 15 ml). The combined

org. fractions were washed with brine (20 ml), dried (MgSO₄), and evaporated. FC (hexane/AcOEt 2 :1) gave

25 (208 mg, 90%). White solid. R_f(hexane/AcOEt 4 :1) 0.45. M.p. 71 728. [a]²_D⁵ À25.3( c 1.0, CHCl₃).

¹H-NMR (300 MHz, CDCl₃): see Table 4. ¹³C-NMR (75 MHz, CDCl₃): see Table 4. EI-MS: 203([ M À Me] ).

Helvetica Chimica Acta Vol. 88 (2005)

1901

X-Ray Analysis of 25⁶). Recrystallisation of 25 in Et₂O/hexane 4 :1 gave crystals suitable for X-ray

analysis: C₉H₁₁ClO₄(218.636); orthorhombic P2₁2₁2₁; a 5.55290(10), b 9.2059(2), c 40.4710(10) ä. V

2068.85 ä³; Z 8; D_calc. 1.404 Mg/m³. Intensities were measured on an Enraf-Nonius CAD-4 diffractometer

with MoK_aradiation (graphite monochromator, l 0.71073ä) at 152 K, q range 0.998 29.5758. Of the 5331

total collected reflections, 5319 independent reflections were observed. R 0.0658, R_w 0.1654.

(Z)-1,5-Anhydro-6,7,8-trideoxy-2,3-O-isopropylidene-8-C-phenyl-b-d-ribo-oct-5-en-7-ynofuranose (26). A

suspension of 22 (50 mg, 0.15 mmol) in dry MeOH (3ml) was treated with one batch of MeONa (30 mg,

0.56 mmol) and kept at reflux for 4 h. After evaporation, the residue was treated with soln. of 0.1m HCl (0.5 ml)

in H₂O (10 ml), and extracted with AcOEt (3 Â 15 ml). The combined org. fractions were washed with brine

(10 ml), dried (MgSO₄), and evaporated. FC (cyclohexane/AcOEt 4 :1) gave 26 (40 mg, 91%). White solid. R_f

(cyclohexane/AcOEt 4 :1) 0.53. M.p. 74 758. [a]_D²⁵ 13.2 (c 1.0, CHCl₃). IR (CHCl₃): 3030w, 3013w, 2939w,

2204w, 1950w, 1683m, 1597w, 1491m, 1456w, 1443w, 1384m, 1376m, 1356m, 1316m, 1231s, 1204m, 1158m, 1138s,

1091s, 1056m, 971m, 925s, 865m. ¹H-NMR (500 MHz, CDCl₃): see Table 4; additionally, 7.45 7.26 (m, 5 arom.

H). ¹³C-NMR (125 MHz, CDCl₃): see Table 4; additionally, 131.35 (d); 128.13(2 d); 127.96 (2d); 123.26 (s). HR-

MALDI-MS: 307.0950 ([M Na] , C₁₇H₁₆NaO₄; calc. 307.0941). Anal. calc. for C₁₇H₁₆O₄(284.31): C 71.96, H

5.81; found: C 71.82, H 5.67.

X-Ray Analysis of 26⁶). Recrystallisation of 26 in Et₂O/hexane 4 :1 gave crystals suitable for X-ray

analysis: C₁₇H₁₆O₄(284.311); orthorhombic P2₁2₁2₁; a 5.5724(2), b 16.1789(5), c 16.5834(5) ä. V

1495.08 ä³; Z 4; D_calc. 1.263Mg/m ³. Intensities were measured on an Enraf-Nonius CAD-4 diffractometer

with MoK_aradiation (graphite monochromator, l 0.71073ä) at 202 K, q range 0.998 31.5078. Of the 4757

total collected reflections, 4738 independent reflections were observed. R 0.0616, R_w 0.1552.

(Z)-1,5-Anhydro-6-C-bromo-6-deoxy-2,3-O-isopropylidene-b-d-ribo-hex-5-enofuranose (27). A suspen-

sion of 23 (100 mg, 0.33 mmol) in dry MeOH (3 ml) was treated with one batch of MeONa (30 mg, 0.56 mmol),

stirred at 228 overnight, and evaporated. The residue was treated with a soln. of 0.1m HCl (0.5 ml) in H₂O

(10 ml) and extracted with AcOEt (3 Â 15 ml). The combined org. fractions were washed with brine (10 ml),

dried (MgSO₄), and evaporated. FC (hexane/AcOEt 4 :1) gave 27 (72 mg, 84%). White solid. R_f(hexane/

AcOEt 4 :1) 0.55. M.p. 118 1198. [a]²_D⁵ À34.9 (c 1.0, CHCl₃). IR (CHCl₃): 3105w, 3029m, 2993m, 2941m,

1692m, 1457m, 1384s, 1376s, 1340m, 1284s, 1233s, 1204s, 1158m, 1122s, 1090s, 1048s, 971s, 927s, 865m, 830m.

¹H-NMR (300 MHz, CDCl₃): see Table 4. ¹³C-NMR (75 MHz, CDCl₃): see Table 4. Anal. calc. for C₉H₁₁BrO₄

(263.09): C 41.09, H 4.21; found: C 41.31, H 4.13.

X-Ray Analysis of 27⁶). Recrystallisation of 27 in Et₂O/hexane 4 :1 gave crystals suitable for X-ray

analysis: C₉H₁₁BrO₄(263.092); orthorhombic P2₁2₁2₁; a 5.6059(2), b 9.3515(3), c 19.8996(7) ä. V

1043.21 ä³; Z 4; D_calc. 1.675 Mg/m³. Intensities were measured on an Enraf-Nonius CAD-4 diffractometer

with MoK_aradiation (graphite monochromator, l 0.71073ä) at 298 K, q range 0.998 26.7338. Of the 2064

total collected reflections, 2051 independent reflections were observed. R 0.0556, R_w 0.1828.

(Z)-1,5-Anhydro-6-deoxy-6-C-iodo-2,3-O-isopropylidene-b-d-ribo-hex-5-enofuranose (28). A suspension

of 24 (36 mg, 0.1 mmol) in dry MeOH (3 ml) was treated with one batch of MeONa (10 mg, 0.2 mmol), stirred

at 228 overnight, and evaporated. The residue was treated with a soln. of 0.1m HCl (0.5 ml) in H₂O (10 ml) and

extracted with AcOEt (3 Â 15 ml). The combined org. fractions were washed with brine (10 ml), dried

(MgSO₄), and evaporated. FC (hexane/AcOEt 4 :1) gave 28 (28 mg, 91%). White solid. R_f(hexane/AcOEt

4 :1) 0.52. M.p. 130 1328. [a]²_D⁵ À24.1 (c 0.96, CHCl₃). IR (CHCl₃): 3095w, 3029w, 3011m, 2983m, 2959m,

1674m, 1457w, 1384m, 1376m, 1340w, 1283m, 1231s, 1228s, 1205s, 1159m, 1113s, 1087s, 1044m, 971m, 927s, 880m,

865s, 829m. ¹H-NMR (300 MHz, CDCl₃): see Table 4. ¹³C-NMR (75 MHz, CDCl₃): see Table 4. HR-EI-MS:

296.0877 (9, [M À Me] , C₈H₈¹²⁸IO₄, calc. 296.0875), 295.0926 (100, [M À Me] , C₈H₈¹²⁶IO₄, calc. 295.0928), 295

([M À Me] ). Anal. calc. for C₉H₁₁IO₄(310.09): C 34.86, H 3.58; found: C 35.00, H 3.66.

X-Ray Analysis of 28⁶). Recrystallisation of 28 in Et₂O/hexane 4 :1 gave crystals suitable for X-ray

analysis: C₉H₁₁IO₄(310.087); orthorhombic P2₁2₁2₁; a 5.6538(2), b 20.4230(6), c 9.4368(3) ä. V

1089.64 ä³; Z 4; D_calc. 1.890 Mg/m³. Intensities were measured on an Enraf-Nonius CAD-4 diffractometer

with MoK_aradiation (graphite monochromator, l 0.71073ä) at 298 K, q range 0.998 28.7008. Of the 5274

total collected reflections, 2798 independent reflections were observed. R 0.0386, R_w 0.1282.

Phenyl 2,3,6-Tri-O-acetyl-4-deoxy-4-C-(4-phenylbuta-1,3-diyn-1-yl)-1-thio-b-d-glucopyranoside (30). A

suspension of [Pd₂(dba)₃] (6 mg, 0.0125 mmol), CuI (2 mg, 0.01 mmol), P(fur)₃(6 mg, 0.0125 mmol), 29 [44]

(253mg, 0.5 mmol), and (bromoethynyl)benzene (91 mg, 0.5 mmol) in DMF (3ml) was degassed twice and

stirred for 5 min at 228. The mixture was treated with Et₃N (0.3ml) and stirred for 12 h at 22 8. The soln. was

diluted with Et₂O (10 ml), treated with H₂O (10 ml), and 0.1m aq. HCl (3ml). The org. layer was washed with

H₂O (2 Â 15 ml), and the aq. layer was extracted with Et₂O (4 Â 10 ml). The combined org. fractions were dried

1902

Helvetica Chimica Acta Vol. 88 (2005)

(MgSO₄) and evaporated. FC (hexane/AcOEt 4 :1) gave 30 (246 mg, 82%). White solid. R_f(hexane/AcOEt

4 :1) 0.46. M.p. 128 1298. [a]²_D⁵ À10.7 (c 1.0, CHCl₃). IR (CHCl₃): 3029w, 3014w, 2953w, 2336w, 1751s,

1600w, 1491w, 1479w, 1441w, 1372w, 1231s, 1227s, 1051m, 909m. ¹H-NMR (300 MHz, CDCl₃): see Table 5;

additionally, 7.50 7.26 (m, 10 arom. H); 2.11 (s, AcO); 2.09 (s, 2 AcO). ¹³C-NMR (75 MHz, CDCl₃): see

Table 5; additionally, 170.37, 169.63, 169.42 (3s, 3 CO); 140.63( s); 133.06 (2d); 132.56 (2d); 129.37 (d); 128.83

(2d); 128.35 (2d); 128.30 (d); 121.05 (s); 20.94 (q, 2 Me); 20.82 (q, Me). HR-MALDI-MS: 529.1297

([M Na] , C₂₈H₂₆NaO₇S ; calc. 529.1291). Anal. calc. for C₂₈H₂₆O₇S (506.58): C 66.21, H 5.26; found: C 66.39,

H 5.17.

Table 5. Selected ¹H- and ¹³C-NMR Chemical Shifts [ppm], and Coupling Constants [Hz] of the 1-Thio-b-d-

glucopyranosides 30 37 in CDCl₃

30

4.71

4.84

5.27

2.97

3.78

4.52

4.29

31

4.69

4.81

5.22

2.79

3.72

4.47

4.24

32

4.68

4.79

5.21

2.78

3.72

4.46

4.22

33

4.68

4.80

5.22

2.91

3.73

4.46

4.24

34

35

36

37

HÀC(1)

HÀC(2)

HÀC(3)

HÀC(4)

HÀC(5)

H_aÀC(6)

H_bÀC(6)

HÀC(2')

HOÀC(2)

HOÀC(3

J(1,2)

4.67

3.35

3.87

2.67

3.80

4.42

4.06

5.15

2.80

2.67

9.6

4.66

3.33

3.84

2.61

3.79

4.39

4.01

5.44

2.76

2.61

9.9

4.65

3.33

3.84

2.56

3.77

4.38

4.01

5.38

2.82

2.67

9.6

4.65

3.33

3.86

2.54

3.79

4.39

4.03

5.16

2.70

2.58

9.6

)

9.9

9.0

9.9

9.0

9.9

9.0

9.9

9.0

J(2,3)

8.7

8.5

8.1

J(3,4)

10.8

11.1

10.8

10.5

10.7

10.5

J(4,5)

10.5

10.4

10.8

2.1

6.6

9.6

8.0

ꢁ 2.0

90.68

73.54

74.47

49.34

10.5

2.4

6.7

9.6

7.8

10.7

2.1

6.9

9.6

7.8

2.7

3.0

90.91

73.77

74.54

49.80

10.5

2.1

6.7

9.7

7.8

2.4

90.63

73.60

74.28

49.90

J(4,2')

J(5,6a)

J(5,6b)

J(6a,6b)

J(2,OH)

J(3

C(1)

C(2)

C(3)

C(4)

C(5)

C(6)

C(1')

C(2')

C(3')

C(4')

2.2

5.4

12.0

2.1

5.7

12.0

2.1

5.7

12.0

2.2

5.7

12.0

2.4

,OH)

ꢁ 2.0

89.06

73.55

74.29

48.99

85.86

70.22

73.28

36.97

76.50

64.11

85.82

70.16

73.41

36.28

76.5376.42

64.06

73.41

85.78

70.17

73.36

37.05

76.88

77.17

75.77

77.50

64.05

73.87

44.81

69.87

161.98

79.83

83.64

91.97

69.60

152.31

90.66

69.86

154.31

77.49

69.61

157.83

43.56

a

)

69.71

73.06

76.25

63.28

^a) Hidden by the signals of CDCl₃.

Phenyl 2,3,6-Tri-O-acetyl-4-C-(2-chloroethynyl)-4-deoxy-1-thio-b-d-glucopyranoside (31). A suspension of

29 (101 mg, 0.25 mmol) in THF (3ml) was cooled to À 788, treated with 1.6m BuLi in hexane (0.2 ml,

0.3mmol), and stirred for 3min. The mixture was transferred via a cannula to a stirred, cooled (À 788) soln. of

NCS (34 mg, 0.32 mmol) in THF (3 ml). The resulting mixture was slowly warmed to ambient temp., when TLC

showed complete conversion. After addition of sat. aq. NH₄Cl soln. (5 ml), the aq. layer was extracted with

AcOEt (3 Â 15 ml). The combined org. fractions were washed with brine (10 ml), dried (MgSO₄), and

evaporated. FC (cyclohexane/AcOEt 4 :1) gave 31 (70 mg, 64%). White solid. R_f(hexane/AcOEt 4 :1) 0.62.

M.p. 123 124 8. [a]_D²⁵ À28.5 (c 1.05, CHCl₃). IR (CHCl₃): 3030w, 3009w, 2957w, 2873w, 2245w, 1752s, 1584w,

Helvetica Chimica Acta Vol. 88 (2005)

1903

1479w, 1440w, 1372m, 1234s, 1227s, 1050s, 954w, 913w, 83 w0. ¹H-NMR (300 MHz, CDCl₃): see Table 5;

additionally, 7.49 7.28 (m, 5 arom. H); 2.10, 2.08, 2.07 (3s, 3AcO). ¹³C-NMR (75 MHz, CDCl₃): see Table 5;

additionally, 170.36, 169.61, 169.40 (3s, 3 CO); 132.93 (2d); 131.70 (s); 128.81 (2d); 128.23( d); 20.92 (q, 2 Me);

20.76 (q, Me). HR-MALDI-MS: 465.0551 (32, [M Na] , C₂₀H₂₁³⁷ClNaO₇S ; calc. 465.0565), 463.0591 (100,

[M Na] , C₂₀H₂₁³⁵ClNaO₇S , calc. 463.0594). Anal. calc. for C₂₀H₂₁ClO₇S (440.90): C 54.48, H 4.80; found: C

54.51, H 5.05.

Phenyl 2,3,6-Tri-O-acetyl-4-C-(2-bromoethynyl)-4-deoxy-1-thio-b-d-glucopyranoside (32). A suspension of

29 (101 mg, 0.25 mmol) and NBS (60 mg, 0.336 mmol) in acetone (3 ml) was treated with AgNO₃(6 mg,

0.036 mmol) and stirred for 30 min at 228. After evaporation, the residue was partitioned between H₂O and

AcOEt. The aq. layer was extracted with AcOEt (3 Â 15 ml). The combined org. fractions were washed with

brine (10 ml), dried (MgSO₄), and evaporated. FC (hexane/AcOEt 4 :1) gave 32 (101 mg, 83%). White solid. R_f

(hexane/AcOEt 4 :1) 0.58. M.p. 84 858. [a]²_D⁵ À28.8 (c 1.04, CHCl₃). IR (CHCl₃): 3029m, 3013m, 2955w,

2871w, 2220w, 1753s, 1584w, 1479w, 1440w, 1372m, 1231s, 1081m, 1050s, 954w, 911m, 828w. ¹H-NMR (300 MHz,

CDCl₃): see Table 5; additionally, 7.47 7.26 (m, 5 arom. H); 2.08, 2.06, 2.04 (3s, 3AcO). ¹³C-NMR (75 MHz,

CDCl₃): see Table 5; additionally, 170.34, 169.56, 169.38 (3s, 3 CO); 132.91 (2d); 131.70 (s); 128.79 (2d); 128.21

(d); 20.92 (q, 2 Me); 20.74 (q, Me). HR-MALDI-MS: 509.0068 (97, [M Na] , C₂₀H₂₁⁸¹BrNaO₇S ; calc.

509.0069), 507.0090 (100, [M Na] , C₂₀H₂₁⁷⁹BrNaO₇S ; calc. 507.0089). Anal. calc. for C₂₀H₂₁BrO₇S (485.35):

C 49.49, H 4.36; found: C 49.64, H 4.34.

Phenyl 2,3,6-Tri-O-acetyl-4-deoxy-4-C-(2-iodoethynyl)-1-thio-b-d-glucopyranoside (33). A soln. of AgNO₃

(65 mg, 0.38 mmol) in H₂O (3ml) was treated with dil. NH ₃/H₂O (1 drop), dropwise with a suspension of 29

(101 mg, 0.25 mmol) in acetone (3ml), NIS (90 mg, 0.4 mmol), and stirred for 30 min (the mixture became

homogeneous after ca. 5 min and then became turbid again). After evaporation, the residue was partitioned

between H₂O and AcOEt. The aq. layers were extracted with AcOEt (3 Â 15 ml). The combined org. layers

were washed with brine (10 ml), dried (MgSO₄), and evaporated. FC (hexane/AcOEt 4 :1) gave 33 (109 mg,

73%). White solid. R_f(hexane/AcOEt 4 :1) 0.62. M.p. 123 124 8. [a]²_D⁵ À121.6 (c 1.04, CHCl₃). IR (CHCl₃):

3030m, 3011m, 2957w, 2872w, 2118w, 1953w, 1752s, 1584w, 1479m, 1440m, 1372s, 1240s, 1081s, 1051s, 953w, 913m,

1

868w, 826w. H-NMR (300 MHz, CDCl₃): see Table 5; additionally, 7.48 7.27 (m, 5 arom. H); 2.09, 2.08, 2.06

(3s, 3AcO). HR-MALDI-MS: 555.9987 (22, [ M Na] , C₂₀H₂₁¹²⁷INaO₇S ; calc. 555.9984), 554.9951 (100,

[M Na] , C₂₀H₂₁¹²⁶INaO₇S ; calc. 554.9950).

Phenyl (Z)-4¹,6-Anhydro-4-deoxy-4-C-(4-phenyl-1-hydroxybut-1-en-3-yn-1-yl)-1-thio-b-d-glucopyranoside

(34). A suspension of 30 (51 mg, 0.1 mmol) in dry MeOH (3ml) was treated with one batch of MeONa (20 mg,

0.37 mmol) and kept at reflux for 4 h. After evaporation, the residue was treated with a soln. of 0.1m HCl

(0.5 ml) in H₂O (10 ml) and extracted with AcOEt (3 Â 15 ml). The combined org. fractions were washed with

brine (10 ml), dried (MgSO₄), and evaporated. FC (hexane/AcOEt 4 :1) gave 34 (29 mg, 76%). R_f(hexane/

AcOEt 4 :1) 0.40. [a]²_D⁵ À114.9 (c 1.02, CHCl₃). IR (CHCl₃): 3586w, 3500 3150w (br.), 3064w, 3029w,

3012m, 2901w, 2199w, 1669m, 1596w, 1490m, 1480m, 1441m, 1360m, 1303w, 1247m, 1177m, 1130m, 1109m,

1

1089m, 1070m, 1044m, 1008s, 914w, 862w, 825w. H-NMR (300 MHz, CDCl₃): see Table 5; additionally, 7.56

7.25 (m, 10 arom. H). ¹³C-NMR (75 MHz, CDCl₃): see Table 5; additionally, 133.04 (2d); 131.23 (2d); 130.80 (s);

129.15 (2d); 128.62 (d); 128.01 (2d); 127.51 (d); 123.76 (s). HR-MALDI-MS: 403.0973 ([M Na] ,

C₂₂H₂₀NaO₄S ; calc. 403.0975). Anal. calc. for C₂₂H₂₀O₄S (380.46): C 69.45, H 5.30; found: C 69.53, H 5.50.

Phenyl (Z)-4¹,6-Anhydro-4-C-(2-chloro-1-hydroxyethenyl)-4-deoxy-1-thio-b-d-glucopyranoside (35). A

suspension of 31 (44 mg, 0.1 mmol) in dry MeOH (3ml) was treated with one batch of MeONa (20 mg,

0.37 mmol) and kept at reflux for 4 h. After evaporation, the residue was treated with a soln. of 0.1m HCl

(0.5 ml) in H₂O (10 ml), and extracted with AcOEt (3 Â 15 ml). The combined org. fractions were washed with

brine (10 ml), dried (MgSO₄), and evaporated. FC (cyclohexane/AcOEt 2 :1) gave 35 (20 mg, 63%). White

solid. R_f(cyclohexane/AcOEt 2 :1) 0.52. M.p. 85 868. [a]²_D⁵ À158.8 (c 1.0, CHCl₃). IR (CHCl₃): 3586m,

3391w (br.), 3113w, 3028w, 3008m, 2960s, 2928s, 2901m, 2873s, 1690w, 1650w, 1583w, 1481m, 1441m, 1383m,

1354m, 1308m, 1284w, 1175m, 1131s, 1110s, 1090m, 1071m, 1034s, 1004s, 893m, 826w. ¹H-NMR (300 MHz,

CDCl₃): see Table 5; additionally, 7.55 7.33 (m, 5 arom. H). ¹³C-NMR (75 MHz, CDCl₃): see Table 5;

additionally, 133.02 (2d); 130.71 (s); 129.16 (d); 128.67 (2d). HR-MALDI-MS: 339.0246 (32, [M Na] ,

C₁₄H₁₅³⁷ClNaO₄S ; calc. 339.0248), 337.0280 (100, [M Na] , C₁₄H₁₅³⁵ClNaO₄S ; calc. 337.0277). Anal. calc. for

C₁₄H₁₅ClO₄S (398.86): C 54.20, H 4.80; found: C 54.16, H 4.82.

Phenyl (Z)-4¹,6-Anhydro-4-C-(2-bromo-1-hydroxyethenyl)-4-deoxy-1-thio-b-d-glucopyranoside (36). A

suspension of 32 (48 mg, 0.1 mmol) in dry MeOH (3ml) was treated with one batch of MeONa (20 mg,

0.37 mmol) and kept at reflux for 4 h. After evaporation, the residue was treated with a soln. of 0.1m HCl

(0.5 ml) in H₂O (10 ml) and extracted with AcOEt (3 Â 15 ml). The combined org. fractions were washed with

1904

Helvetica Chimica Acta Vol. 88 (2005)

brine (10 ml), dried (MgSO₄), and evaporated. FC (cyclohexane/AcOEt 2 :1) gave 36 (27 mg, 74%). R_f

(cyclohexane/AcOEt 2 :1) 0.46. [a]²_D⁵ À93.6 (c 1.0, CHCl₃). IR (CHCl₃): 3524w (br.), 3450w (br.), 3029s,

2986s, 2941m, 2907m, 2875m, 1732s, 1573w, 1478w, 1465s, 1446s, 1374s, 1251s, 1197m, 1158m, 1096s, 1046s,

1

1004m, 940m, 918m, 847m. H-NMR (300 MHz, CDCl₃): see Table 5; additionally, 7.54 7.26 (m, 5 arom. H).

¹³C-NMR (75 MHz, CDCl₃): see Table 5; additionally, 133.37 (2d); 131.06 (s); 129.52 (2d); 129.02 (d). HR-

MALDI-MS: 382.9758 (97, [M Na] , C₁₄H₁₅⁸¹BrNaO₄S ; calc. 382.9752), 380.9776 (100, [M Na] ,

C₁₄H₁₅⁷⁹BrNaO₄S ; calc. 380.9772). Anal. calc. for C₁₄H₁₅BrO₄S (359.24): C 46.81, H 4.21; found: C 46.85, H

4.36.

Phenyl (Z)-4¹,6-Anhydro-4-deoxy-4-C-(1-hydroxy-2-iodoethenyl)-1-thio-b-d-glucopyranoside (37). A sus-

pension of 33 (53mg, 0.1 mmol) in dry MeOH (3ml) was treated with one batch of MeONa (20 mg, 0.37 mmol)

and kept at reflux for 4 h. After evaporation, the residue was treated with a soln. of 0.1m HCl (0.5 ml) in H₂O

(10 ml), and extracted with AcOEt (3 Â 15 ml). The combined org. fractions were washed with brine (10 ml),

dried (MgSO₄), and evaporated. FC (cyclohexane/AcOEt 2 :1) gave 37 (26 mg, 64%) R_f(cyclohexane/AcOEt

2 :1) 0.45. M.p. 66 678. [a]²_D⁵ À99.7 (c 0.98, CHCl₃). IR (CHCl₃): 3587w (br.), 3416w (br.), 3027w, 2984m,

1731s, 1478w, 1441w, 1375s, 1249s, 1110m, 1046s, 940w, 846w. ¹H-NMR (300 MHz, CDCl₃): see Table 5;

additionally, 7.54 7.32 (m, 5 arom. H). ¹³C-NMR (75 MHz, CDCl₃): see Table 5; additionally, 133.03 (2d);

130.69 (s); 129.16 (2d); 128.66 (d). HR-ESI-MS: 429.9687 (16, [M Na] , C₁₄H₁₅¹²⁷INaO₄S ; calc. 429.9689),

428.9625 (100, [M Na] , C₁₄H₁₅¹²⁶INaO₄S ; calc. 428.9628).

Phenyl 6-O-Acetyl-2,3-di-O-benzyl-4-deoxy-4-C-(4-phenylbuta-1,3-diyn-1-yl)-1-thio-a-d-glucopyranoside

(39). A suspension of [Pd₂(dba)₃] (6 mg, 0.0125 mmol), CuI (2 mg, 0.01 mmol), P(fur)₃(6 mg, 0.0125 mmol),

38 [30] (251 mg, 0.5 mmol) and (bromoethynyl)benzene (91 mg, 0.5 mmol) in DMF (3 ml) was degassed twice

and stirred at 228 for 5 min. The mixture was treated with Et₃N (0.3ml) and stirred for 12 h at 22 8. The soln. was

diluted with Et₂O (10 ml), and treated with H₂O (10 ml) and 0.1m aq. HCl (3ml). The org. layer was washed

with H₂O (2 Â 15 ml), and the aq. layer was extracted with Et₂O (4 Â 10 ml). The combined org. fractions were

dried (MgSO₄) and evaporated. FC (hexane/AcOEt 4 :1) gave 39 (246 mg, 82%). Pale yellow solid. R_f(hexane/

AcOEt 4 :1) 0.48. M.p. 126 1288. [a]²_D⁵ À149.6 (c 1.0, CHCl₃). IR (CHCl₃): 3066w, 3032m, 3012m, 2245w,

2144w, 1951w, 1880w, 1741s, 1584w, 1491m, 1481m, 1454m, 1441m, 1368m, 1239s, 1206w, 1126s, 1087s, 1038s,

1028s, 910w. ¹H-NMR (300 MHz, CDCl₃): see Table 6; additionally, 7.53 7.26 ( m, 20 arom. H); 4.95 (s, PhCH₂);

4.78, 4.72 (2d, J 11.7, PhCH₂); 2.02 (s, AcO). ¹³C-NMR (75 MHz, CDCl₃): see Table 6; additionally, 170.48 (s,

CO); 137.93, 137.43, 133.56 (3s); 132.54 (2d); 131.67 (2d); 127.33 129.20 (several d); 121.40 (s); 76.61, 72.62

(2t, 2 PhCH₂); 20.90 (q, Me). MALDI-MS: 625 ([M Na] ). HR-MALDI-MS: 625.2012 ([M Na] ,

C₃₈H₃₄NaO₅S ; calc. 625.2019). Anal. calc. for C₃₈H₃₄O₅S (602.75): C 75.72, H 5.69; found: C 75.94, H 5.96.

Treatment of 39 with MeONa. A suspension of 39 (60 mg, 0.1 mmol) in dry MeOH (3ml) was treated with

one batch of MeONa (20 mg, 0.37 mmol) and kept at reflux for 4 h. After evaporation, the residue was treated

with a soln. of 0.1m HCl (0.5 ml) in H₂O (10 ml), and extracted with AcOEt (3 Â 15 ml). The combined org.

fractions were washed with brine (10 ml), dried (MgSO₄), and evaporated. FC (hexane/AcOEt 4 :1) gave 41

(28 mg, 51%) and 40 (17 mg, 30%).

Data of Phenyl (Z)-4¹,6-Anhydro-2,3-di-O-benzyl-4-deoxy-4-C-(1-hydroxy-4-phenylbut-1-en-3-yn-1-yl)-1-

thio-a-d-galactopyranoside (40). R_f(hexane/AcOEt 4 :1) 0.52. [a]²_D⁵ 11.8 (c 1.0, CHCl₃). IR (CHCl₃):

3066w, 3030m, 3014s, 2930w, 2195w, 1951w, 1879w, 1807w, 1648s, 1596m, 1584m, 1489m, 1481m, 1454m, 1440w,

1354w, 1293w, 1262m, 1172s, 1091s, 1047s, 1027s, 999m, 987m, 93 w1, 911w, 872w, 842w, 820w. ¹H-NMR

(500 MHz, C₆D₆): see Table 6; additionally, 7.52 7.46 (m, 2 arom. H); 7.42 7.34 (m, 2 arom. H); 7.29 7.24 (m, 4

arom. H); 7.16 7.01 (m, 8 arom. H); 6.99 6.82 (m, 4 arom. H); 4.51, 4.46 (2d, J 11.7, PhCH₂); 4.34, 4.29 (2d,

J 11.4, PhCH₂); 4.18 (t, J ꢂ 3.0, irrad. at 4.01 ! NOE of 3.9%, HÀC(5)); 4.11 (dd, J 10.0, 4.8, irrad. at

5.98 ! NOE of 2.4%, HÀC(2)); 3.42 (dd, J 10.1, 2.5, irrad. at 4.18 ! NOE of 3.8%, H'ÀC(6)); 2.72 (dt, J ꢂ

5.6, 3.4, irrad. at 5.98 ! NOE of 2.6%, irrad. at 4.18 ! NOE of 7.4%, irrad. at 4.01 ! NOE of 12%, HÀC(4)).

¹³C-NMR (125 MHz, C₆D₆): see Table 6; additionally, 138.59 (2s); 135.35 (s); 131.46 (2d), 130.67 (2d); 129.16

(2d); 126.86 128.63(several d); 125.33 (s); 73.23, 72.77 (2t, 2 PhCH₂). MALDI-MS: 583([ M Na] ). HR-

MALDI-MS: 583.1920 ([M Na] , C₃₆H₃₂NaO₄S ; calc. 583.1914).

Data of Phenyl (E)-4¹,6-Anhydro-2,3-di-O-benzyl-4-deoxy-4-C-(1-hydroxy-4-phenylbut-1-en-3-yn-1-yl)-1-

thio-a-d-galactopyranoside (41). R_f(hexane/AcOEt 4 :1) 0.62. [a]²_D⁵ 37.3 ( c 1.0, CHCl₃). IR (CHCl₃):

3066w, 3033w, 3013s, 2930m, 2893w, 2196w, 1950w, 1878w, 1807w, 1731w, 1648m, 1595w, 1584w, 1489m, 1481m,

1

1454m, 1440w, 1377m, 1350w, 1307m, 1262m, 1173m, 1101s, 1067m, 1047s, 1027s, 999m, 987m, 93 1w. H-NMR

(300 MHz, CDCl₃): see Table 6; additionally, 7.54 7.19 (m, 20 arom. H); 4.93( ddd, J 7.0, 5.9, 3.2, irrad. at

3.68 ! NOE of 10.5%, HÀC(5)); 4.77 (d, J 12.0), 4.565 (d, J 11.8) (PhCH₂); 4.570 (dd, J ꢂ 5.7, 4.2, irrad. at

3.68 ! NOE of 7.5%, HÀC(3)); 4.558 (d, J 11.4), 4.47 (d, J 12.0) (PhCH₂); 4.22 (dd, J 10.0, 6.0, irrad. at

Helvetica Chimica Acta Vol. 88 (2005)

1905

Table 6. Selected ¹H- and ¹³C-NMR Chemical Shifts [ppm], and Coupling Constants [Hz] of the 1-Thio-b-d-

glucopyranosides 39 44

39

40^a)

41^a)

42

43

44 (Glc)

44 (Gal)

CDCl₃

C₆D₆

CDCl₃

HÀC(1)

HÀC(2)

HÀC(3)

HÀC(4)

HÀC(5)

H_aÀC(6)

H_bÀC(6)

HÀC(2')

J(1,2)

5.64

3.80

3.92

2.85

4.57

4.35

4.31

5.65

5.735.64

5.60

5.61

5.65

4.11

4.01

2.72

4.18

3.91

3.42

5.98

4.8

3.64

4.57

3.68

4.93

4.36

4.22

5.34

5.0

3.79

3.90

2.79

4.56

4.33

4.29

3.75

3.88

2.81

4.35

3.76

3.89

2.81

4.36

4.20 4.13

3.53^b)

4.20 4.13

4.11

3.87 3.70

3.94 3.84

3.82 3.72

5.31^c)

5.5

5.4

5.1

9.9

5.4

9.7

4.0

d

)

J(2,3 9.310.0

J(3,4)

J(4,5)

4.2

9.39.3

9.3

5.7

7.0

)

d

9.9

10.8

5.6

3.4

9.9

10.5

d

10.5

J(4,2')

J(5,6a)

J(5,6b)

J(6a,6b)

C(1)

C(2)

C(3)

C(4)

C(5)

2.2

0

2.5

10.1

87.29

76.76

75.10

46.11

72.13

74.27

1.9

3.1

6.0

10.0

85.31

74.14

71.60

43.46

70.21

75.19

1.5

)

2.7

10.0

d

4.2

3.6

11.1

86.99

79.52^e)

79.40^e)

38.20

69.34

64.32

3.6

2.4

10.8

86.90

2.1

4.8

)

87.10

79.54^e)

79.03^e)

37.39

71.66

62.94

3.0

5.4

)

d

79.33^e)

78.99^e)

37.86

69.24

64.21

C(6)

C(1')

C(2')

C(3')

C(4')

79.03164.21368.59

74.82

75.10

68.49

68.94

73.67

76.16

81.61

86.70

92.64

80.85

87.00

92.30

68.35

^a) Assignment based on selective homodecoupling experiments, and a HSQC and a HMBC spectrum.

^b) J(2',HÀC(4) of Glc) 1.5 Hz. ^c) Br. s; w_1/2 8.7 Hz. ^d) Not assigned. ^e) Assignments may be interchanged.

4.93 ! NOE of 3.5%, H'ÀC(6)); 3.68 (ddd, J ꢂ 7.2, 5.6, 1.8, irrad. at 4.93 ! NOE of 9%, HÀC(4)); no NOE

observed upon irrad. at 5.34. ¹³C-NMR (75 MHz, CDCl₃): see Table 6; additionally, 137.73, 137.02, 135.74 (3s);

130.65 (2d), 130.09 (2d); 128.95 126.50 (several d); 124.13( s); 74.37, 73.73 (2t, 2 PhCH₂). MALDI-MS: 583

([M Na] ). HR-MALDI-MS: 583.1919 ([M Na] , C₃₆H₃₂NaO₄S ; calc. 583.1914).

4,4'-(Buta-1,3-diyne-1,4-diyl)bis(phenyl 6-O-Acetyl-2,3-di-O-benzyl-4-deoxy-1-thio-a-d-glucopyranoside)

(42). Under Ar, a soln. of Cu(OAc)₂(6.7 g, 36.88 mmol) in pyridine (72 ml) was stirred at 608 for 3h, treated

with a soln. of 38 (900 mg, 1.84 mmol) in pyridine (10 ml), stirred for 1 h, cooled to r.t., and evaporated.

Pyridine was removed by two co-distillations with toluene. FC (hexane/AcOEt 5 :1 ! 1:1) gave 42 (795 mg,

88%). R_f(hexane/AcOEt 1 :1) 0.38. ¹H-NMR (75 MHz, CDCl₃): see Table 6; additionally, 7.50 7.24 (m, 15

arom. H); 4.93( d, J 10.8), 4.88 (d, J 10.5), 4.77 (d, J 12.0), 4.71 (d, J 11.7) (4 PhCH); 2.01 (s, AcO).

¹³C-NMR (75 MHz, CDCl₃): see Table 6; additionally, 170.40 (s, CO); 137.86, 137.38 (2s); 133.48 (s); 131.66

(2d); 128.91 (2d); 128.40 (2d); 128.30 (2d); 128.14 (2d); 127.98 (2d); 127.93, 127.76, 127.31 (3d); 76.11, 72.57 (2t, 2

PhCH₂); 20.87 (q, Me). MALDI-MS: 1025 ([M Na] ).

4,4'-(Buta-1,3-diyne-1,4-diyl)bis(phenyl 2,3-Di-O-benzyl-4-deoxy-1-thio-a-d-glucopyranoside) (43). A

soln. of 42 (600 mg, 0.6 mmol) in THF/MeOH/H₂O 4 :4 :1 (45 ml) was treated with 1m MeONa in MeOH

(3ml), heated for 15 min to 60 8, cooled to r.t., treated with Amberlite IR-120 (H form), and stirred for 5 min.

Filtration, evaporation of the filtrate, and FC (hexane/AcOEt 5 :1 ! 1:1) gave 43 (549 mg, 99%). R_f(hexane/

AcOEt 1:1) 0.47. ¹H-NMR (75 MHz, CDCl₃): see Table 6; additionally, 7.49 7.26 (m, 15 arom. H); 4.92 (d, J

11.1), 4.88 (d, J 11.1), 4.77 (d, J 11.7), 4.71 (d, J 11.7) (4 PhCH); 1.57 (br. s, OH). ¹³C-NMR (75 MHz,

1906

Helvetica Chimica Acta Vol. 88 (2005)

CDCl₃): see Table 6; additionally, 137.96, 137.44 (2s); 133.40 (s); 132.03 (2d); 128.98 (2d); 128.37 (2d); 128.26

(2d); 128.09 (2d); 127.98 (2d); 127.89, 127.68, 127.46 (3d); 75.95, 72.66 (2t, 2 PhCH₂). MALDI-MS: 941 ([M

Na] ).

Treatment of 43 with Na₂S ¥ 9 H₂O. A soln. of 43 (50 mg, 32.6 mmol) in MeOCH₂CH₂OH (3ml) was treated

with Na₂S ¥ 9 H₂O (8 mg, 32.6 mmol), kept for 30 min at reflux, and cooled to 238. The suspension was diluted

with AcOEt (0.5 ml) and hexane (0.8 ml), stirred for 30 min at 238, and filtered over Celite. Evaporation of the

filtrate and FC (hexane/AcOEt 20 :1 ! 10 :1) gave a unknown 4 :3:2 mixture (5.5 mg, ca. 10%) and 44 (10 mg,

20%).

Data of Phenyl 2,3-Di-O-benzyl-4-deoxy-4-[(Z)-4-(phenyl 2,3-Di-O-benzyl-4-deoxy-1-thio-a-d-galacto-

pyranosid-4-C,6-O-ylidene)but-3-en-1-yn-1-yl]-1-thio-a-d-glucopyranoside (44). R_f(toluene/AcOEt 2 :1) 0.48.

¹H-NMR (300 MHz, CDCl₃): see Table 6; additionally, 7.55 7.21 (m, 30 arom. H); 4.88 (2d, J 10.2, PhCH₂);

4.82 4.70 (m, 6 PhCH); 1.72 (t, J 6.6, HOÀC(6)).

Data of the 4 :3 :2 Mixture. R_f(toluene/AcOEt 2 :1) 0.69. ¹H-NMR (300 MHz, CDCl₃): 5.79 (s, 0.2 H), 5.72

(d, J 10.2, 0.2 H), 5.68 (d, J 4.5, 0.8 H), 5.66 (d, J ꢂ 4.8, 1.2 H) (2 HÀC(1)); 5.18 (d, J 1.0, 0.4 H); 5.14 (t,

J ꢂ 1.5, 0.6 H) (1 olef. H); 3.43 (td, J ꢂ 6.3, 2.5, 0.4 H), 3.33 (br. t, J 10.5, 0.2 H), 2.92 (td, J 10.5, 2.5, 0.6 H)

(1.2 HÀC(4)).

Allyl 2,3-Di-O-benzyl-4,6-bis-O-(4-methoxybenzyl)-b-d-galactopyranoside (46). A soln. of 45 [63] (80 mg,

0.2 mmol) in DMF (5 ml) was cooled to 08 and treated with 60% NaH in mineral oil (26 mg, 0.67 mmol) in small

portions. After the evolution of gas had ceased (ca. 30 min), the mixture was treated with 4-methoxybenzyl

chloride (0.1 ml, 0.73mmol) and Bu ₄NI (4 mg, 0.01 mmol), stirred at r.t. for 16 h, diluted with Et₂O (10 ml), and

treated dropwise with H₂O (5 ml). The layers were separated, and the org. layer was washed with brine, dried

(MgSO₄), and evaporated. FC (cyclohexane/AcOEt 8 :1) gave 46 (115 mg, 90%). R_f(cyclohexane/AcOEt 4 :1)

0.52. [a]²_D⁵ À10.5 (c 1.10, CHCl₃). IR (CHCl₃): 3020s, 2958m, 2937m, 2912m, 2860m, 2839m, 1884w, 1612s,

1586m, 1513s, 1465m, 1442m, 1421w, 1384w, 1361m, 1302m, 1248s, 1173s, 1110m, 1072m, 1035s, 1011w, 919w,

895w, 825w. ¹H-NMR (300 MHz, CDCl₃): see Table 7; additionally, 7.40 7.18 (m, 14 arom. H); 6.93 6.78 ( m, 4

arom. H); 5.95 (dddd, J 17.2, 10.5, 6.0, 5.4, CH₂ CH); 5.33 (dq, J 17.1, 1.8), 5.18 (dq, J 10.8, 1.8) (CH₂

CH); 4.95 (d, J 11.1), 4.86 (d, J 11.4), 4.77 (d, J 10.5), 4.76 (d, J 12.0), 4.70 (d, J 12.0), 4.58 (d, J

11.4), 4.41 (d, J ꢂ 11.2), 4.35 (d, J 11.1) (8 ArCH); 4.41 (ddt, J 12.9, 5.1, 1.8), 4.12 (ddt, J 12.9, 6.0, 1.5)

(CH₂CHCH₂); 3.81, 3.79 (2s, 2 MeO). ¹³C-NMR (75 MHz, CDCl₃): see Table 7; additionally, 159.14, 158.95

(2s); 138.63, 138.45 (2s); 134.11 (d, CH₂CH); 130.72, 129.90 (2s); 129.84 127.40 (several d); 116.89 (t,

CH₂CH); 113.74 (2d); 113.45 (2d); 75.25, 73.94, 73.18, 72.99 (4t, 4 ArCH₂); 70.11 (t, CH₂CHCH₂); 55.30,

55.27 (2q, 2 MeO). MALDI-MS: 663([ M Na] ). HR-MALDI-MS: 663.2920 ([M Na] , C₃₉H₄₄NaO₈

;

calc. 663.2928). Anal. calc. for C₃₉H₄₄O₈(640.77): C 73.10, H 6.92; found: C 73.11, H 7.05.

2,3-Di-O-benzyl-4,6-bis-O-(4-methoxybenzyl)-d-galactopyranose (47). A suspension of [Ir(COD)(PPh₂-

Me)PF₆] (6 mg, 0.007 mmol) in dry THF (3ml) was degassed and stirred under H ₂for 10 min at 258 (red

suspension turned into yellow soln.). After replacement of H₂by Ar, the yellow soln. was treated with a soln. of

46 (110 mg, 0.225 mmol) in THF (5 ml), stirred for 1 h, treated with H₂O (10 ml) and I₂(114 mg, 0.45 mmol),

stirred for 1 h, and treated with chilled 5% Na₂S₂O₃soln. (10 ml). After evaporation, a soln. of the residue in

AcOEt was washed with brine, dried (MgSO₄), and evaporated. FC (cyclohexane/AcOEt 5 :1) gave 47 (85 mg,

82%). R_f(cyclohexane/AcOEt 2 :1) 0.55. [a]²_D⁵ 4.3( c 1.10, CHCl₃). IR (CHCl₃): 3416w (br.), 3021s, 3014s,

2936w, 2914w, 2873w, 2839w, 1612m, 1586w, 1514s, 1465w, 1455w, 1363w, 1302m, 1249s, 1173m, 1154w, 1093s,

1037s, 909m, 827w. ¹H-NMR (300 MHz, CDCl₃; a-d-47/b-d-47 55 :45): 7.49 7.30 (m, 7 arom. H); 7.38 7.19 (m,

7 arom. H); 6.88 6.81 (m, 4 arom. H); 5.29 (t, J ꢂ 3.2, addn. of D₂O ! d, J 3.2, 0.55 HÀC(1)); 4.93( d, J

10.8, 0.55 H), 4.86 (d, J 11.4, 0.45 H), 4.85 (d, J 11.7, 0.55 H), 4.82 (d, J 12.0, 0.45 H), 4.80 (d, J 12.0,

0.55 H), 4.77 (d, J 12.0, 0.45 H), 4.75 (d, J 10.5, 0.55 H), 4.73( d, J 10.5, 0.45 H), 4.71 (d, J 10.5,

0.55 H), 4.70 (d, J 11.7, 0.45 H) (5 PhCH); 4.65 (dd, J 7.5, 6.6, addn. of D₂O ! d, J 7.5, 0.45 HÀC(1)); 4.55

(d, J 11.4, 0.45 H), 4.53( d, J 11.1, 0.55 H), 4.43(br. d, J 11.7, 1 H), 4.33 (d, J 11.7, 0.55 H), 4.32 (d, J

11.7, 0.45 H) (3PhC H); 4.15 (t, J ꢂ 6.4, 0.55 HÀC(5)); 4.03( dd, J 9.3, 3.6, 0.55 HÀC(2)); 3.93 (br. s, 0.55

HÀC(4)); 3.91 (dd, J 9.3, 2.7, 0.55 HÀC(3)); 3.85 (d, J 3.0, 0.45 HÀC(4)); 3.80, 3.795, 3.79 (3s, 2 MeO);

3.765 (dd, J 9.6, 7.5, 0.45 HÀC(2)); 3.760 (d, J 6.6, exchanged with D₂O, 0.45 HOÀC(1)); 3.60 3.45 (m,

0.45 HÀC(5), 1.55 HÀC(6)); 3.435 (dd, J 9.3, 2.5, 0.45 HÀC(3)); 3.420 (dd, J 9.3, 6.9, 0.45 HÀC(6)); 3.38

(d, J 2.4, exchanged with D₂O, 0.55 HOÀC(1)). ¹³C-NMR (75 MHz, CDCl₃, a-d-47/b-d-47 55 :45): signals of

a-d-47: 159.15, 159.06 (2s); 138.59, 138.20 (2s); 130.62 (s); 129.87 (2d); 129.84 (s); 129.56 (2d); 128.31 (2d);

128.23(2 d); 127.92 (2d); 127.68 (d); 127.48 (d); 127.42 (2d); 113.74 (2d); 113.58 (2d); 91.84 (d, C(1)); 78.80 (d,

C(3)); 76.62 (d, C(2)); 74.19 (t, PhCH₂); 74.17 (d, C(4)); 73.46, 73.12, 72.94 (3t, 3 PhCH₂); 69.52 (d, C(5)); 68.79

(t, C(6)); 55.32 (q, 2 MeO); signals of b-d-47: 159.19, 159.06 (2s); 138.54, 138.35 (2s); 130.56 (s); 129.84 (2d);

Helvetica Chimica Acta Vol. 88 (2005)

1907

Table 7. Selected ¹H- and ¹³C-NMR Chemical Shifts [ppm], and Coupling Constants [Hz] of the d-

Galactopyranose Derivatives 46 and 48 54 in CDCl₃

46

48

49

50

51

52^a)

53^a)^b)

54^a)

HÀC(1)

HÀC(2)

HÀC(3)

HÀC(4)

HÀC(5)

H_aÀC(6)

H_bÀC(6)

HOÀC(4)

HOÀC(6)

HÀC(2')

J(1,2')

J(1,2)

J(2,3)

J(3,4)

J(4,5)

J(5,6_a)

J(5,6_b)

J(6_a,6_b)

J(4,OH)

J(5,OH)

J(6_a,OH)

J(6_b,OH)

C(1)

4.41

3.87

3.58 3.47

4.62

3.86

4.034.01

3.87

3.48

4.034.04

3.43

3.95

3.79

2.70

2.24

4.15

4.06

3.45

3.96

3.79

2.64

2.11

2.54

2.1

4.29

4.24

4.28

4.46

3.86

4.14

4.30

3.67

3.61

3.87

3.50

3.91

3.51

3.75 3.73

3.73 3.71

3.77

3.75

3.77

3.74

4.59

4.60

4.55

3.47

3.94

3.80

2.73

2.28

3.98

3.79

3.68

4.00

3.83

3.73

4.11

4.31

4.20

3.58 3.47

1.77

5.21

0.9

1.78

4.81

0.6

4.83

ꢁ 1.0

7.5

8.1

4.2

9.6

9.0

3.3

1.8

6.6

4.5

9.9

8.7

3.0

1.0

6.6

4.5

11.7

2.0

1.0

9.6

9.0

3.3

1.2

6.6

4.5

11.7

1.5

1.0

2.4

2.0

c

9.6

2.4

1.2

8.1

5.7

9.0

)

ꢁ 2.0

ꢁ 1.0

6.3

1.5

6.9

7.2

11.4

ꢁ 1.0

6.5

ꢁ 1.0

1.8

7.8

7.2

11.1

6.3

11.1

c

)

11.7

1.5

4.5

8.4

70.30

78.47

81.29

67.76

77.97

62.86

4.8

8.7

69.70

3.3

7.5

70.50

4.5

7.5

4.5

7.2

102.89

79.61

82.42

73.45

72.84

68.59

169.87

77.43^d)

80.13

69.56

80.02

80.35

71.09

74.84

61.97

69.77

80.10

80.59

71.22

74.94

62..415363

159.61

82.35

83.25

93.47

69.71

79.96

80.36

71.54

72.62

d

C(2)

C(3)

C(4)

C(5)

C(6)

C(1')

C(2')

C(3')

78.1378.06

)

81.37

67.62

77.99

62.86

81.42

71.96

67.60

77.31^d)

67.17

78.03^d)

62.79

e

102.1380.74

91.11 74.15

79.08

)

152.33

78.37

159.14

82.60

83.14

93.87

70.70

73.21

C(4')

78.70^e)

^a) Same numbering as 50 and 51. ^b) Assignment based on a DQFCOSY, a HSQC, and a HMBC spectrum.

d

^c) Not assigned.

)

^e) Assignments may be interchanged.

129.73( s); 129.61 (2d); 128.32 (4d); 128.10 (2d); 127.54 (d); 127.52 (d); 127.46 (2d); 113.77 (2d); 113.58 (2d);

97.76 (d, C(1)); 82.25 (d, C(3)); 80.80 (d, C(2)); 75.11, 74.07 (2t, 2 PhCH₂); 73.62 (d, C(4)); 73.20 (t, PhCH₂);

73.01 (d, C(5)); 72.94 (t, PhCH₂); 68.68 (t, C(6)); 55.32 (q, 2 MeO). MALDI-MS: 623([ M Na] ). HR-

MALDI-MS: 623.2614 ([M Na] , C₃₆H₄₀NaO₈; calc. 623.2615).

2,3-Di-O-benzyl-4,6-bis-O-(4-methoxybenzyl)-d-galactono-1,5-lactone (48). A suspension of 47 (672 mg,

1.12 mmol) in DMSO (6 ml) was treated with Ac₂O (3ml) and stirred for 6 h. The clear yellow soln. was added

dropwise to cold stirred H₂O. After extraction with CH₂Cl₂, evaporation and crystallisation from hexane gave 48

(590 mg, 88%). R_f(cyclohexane/AcOEt 5 :1) 0.45. [a]²_D⁵ 151.4 (c 1.0, CHCl₃). IR (CHCl₃): 3067w, 3021s,

3014m, 2959w, 2936w, 2914w, 2875w, 2839w, 1748s, 1612m, 1586w, 1514s, 1465m, 1455m, 1442w, 1361m, 1302m,

1249s, 1174m, 1103s, 1061m, 1035s, 910w, 847w, 824w. ¹H-NMR (300 MHz, CDCl₃): see Table 7; additionally,

7.49 7.30 (m, 10 arom. H); 7.29 7.10 (m, 4 arom. H); 6.91 6.80 (m, 4 arom. H); 5.18 (d, J 11.4), 4.84 (d, J

10.8), 4.78 (d, J 11.1), 4.74 (d, J 12.6), 4.67 (d, J 12.0), 4.54 (d, J 10.8), 4.46 (d, J 11.4), 4.39 (d, J

11.7) (8 PhCH); 3.80, 3.79 (2s, 2 MeO). ¹³C-NMR (75 MHz, CDCl₃): see Table 7; additionally, 159.29, 159.18

(2s); 137.69, 137.44 (2s); 129.78 (s); 129.60 (2d); 129.56 (2d); 129.36 (s); 128.36 (2d); 128.33 (2d); 128.25 (2d);

1908

Helvetica Chimica Acta Vol. 88 (2005)

127.77 (d); 127.68 (d); 127.38 (2d); 113.80 (2d); 113.67 (2d); 75.27, 74.30, 73.30, 72.72 (4t, 4 PhCH₂); 55.30 (2

MeO). MALDI-MS: 621 ([M Na] ). HR-MALDI-MS: 621.2467 ([M Na] , C₃₆H₃₈NaO₈; calc. 621.2459).

Anal. calc. for C₃₆H₃₈O₈(598.69): C 72.22, H 6.40; found: C 72.23, H 6.51.

1-(2,3-Di-O-benzyl-b-d-galactopyranosyl)-2-(trimethylsilyl)ethyne (49). Under Ar, a stirred and cooled

(À 788) soln. of Me₃SiCꢀCH (0.3ml, 2 mmol) in THF (8 ml) was treated dropwise with 1.6 m BuLi in hexane

(1.2 ml) over a period of 0.5 h and stirred for 1 h. This soln. was transferred into a cooled (À 788) soln. of 48

(240 mg, 0.4 mmol) in THF (8 ml) over a period of 10 min with a canula. The resulting pale brown soln. was

stirred for 4 h at À 788, treated with sat. aq. NH₄Cl soln. (2 ml), warmed to r.t., stirred for 0.5 h, and worked up

(AcOEt). After evaporation, a soln. of the residue (280 mg) in CH₂Cl₂/MeCN 1 :1 (5 ml) was cooled to À 408,

treated with a soln. of BF₃¥ Et₂O (0.3ml, 2.3mmol) and Et ₃SiH (0.6 ml, 3.6 mmol) in CH₂Cl₂/MeCN 1:1 (5 ml)

using a canula over a period of 0.5 h. The mixture was stirred at À 408 for 1 h and at À 10 to À 158 for 16 h,

treated with sat. aq. NaHCO₃soln. (5 ml), stirred for 1 h at À 10 to À 158, and worked up (AcOEt).

Evaporation and FC (cyclohexane/AcOEt 5 :1) gave 49 (101 mg, 63%). Pale yellow oil. R_f(cyclohexane/AcOEt

5 :1) 0.42. [a]²_D⁵ À 52.6 (c 1.1, CHCl₃). IR (CHCl₃): 3577w (br.), 3350w (br.), 3090w, 3067w, 3032w, 3013m,

2961m, 2876m, 2180w, 1951w, 1875w, 1810w, 1732w, 1606w, 1497w, 1454m, 1365m, 1297m, 1251s, 1091s, 1028m,

910w, 846s. ¹H-NMR (300 MHz, CDCl₃): see Table 7; additionally, 7.42 7.28 (m, 10 arom. H); 4.99 (d, J 10.5),

4.83( d, J 10.5) (PhCH₂); 4.73( s, PhCH₂); 0.19 (s, Me₃Si). ¹³C-NMR (75 MHz, CDCl₃): see Table 7;

additionally, 137.95, 137.49 (2s); 128.45 (2d); 128.25 (2d); 128.07 (2d); 127.95 (2d); 127.72 (2d); 75.78, 72.36 (2t, 2

PhCH₂); 0.16 (q, Me₃Si). MALDI-MS: 463([ M Na] ). HR-MALDI-MS: 463.1906 ([M Na] ,

C₂₅H₃₂NaO₅Si ; calc. 463.1911).

(2,3-Di-O-benzyl-b-d-galactopyranosyl)ethyne (50). A suspension of 49 (88 mg, 0.2 mmol) in dry MeOH

(5 ml) was treated with one batch of MeONa (20 mg, 0.37 mmol), kept at reflux for 10 h, and evaporated. The

residue was treated with a soln. of 0.1m HCl (0.5 ml) in H₂O (10 ml), and extracted with AcOEt (3 Â 15 ml).

The combined org. fractions were washed with brine (10 ml), dried (MgSO₄), and evaporated. Crystallisation

from i-PrOH gave 50 (68 mg, 93%). White solid. M.p. 133 1348. [a]²_D⁵ À52.6 (c 1.1, CHCl₃). IR (CHCl₃):

3572w (br.), 3307w, 3031w, 3009w, 2929w, 2853w, 2256w, 1603w, 1497w, 1454w, 1374s, 1298w, 1265s, 1249s, 1093s,

1046m, 1002w, 941w, 918w, 846w. ¹H-NMR (300 MHz, CDCl₃): see Table 7; additionally, 7.40 7.26 (m, 10 arom.

H); 4.99, 4.84 (2d, J 10.5, PhCH₂); 4.73( s, PhCH₂). ¹³C-NMR (75 MHz, CDCl₃): see Table 7; additionally,

137.82, 137.41 (2s); 128.48 (2d); 128.27 (2d); 128.14 (2d); 127.99, 127.78 (2d); 127.75 (2d); 75.81, 72.30 (2t, 2

PhCH₂). MALDI-MS: 391 ([M Na] ). HR-MALDI-MS: 391.1521 ([M Na] , C₂₂H₂₄NaO₅; calc.

391.1516). Anal. calc. for C₂₂H₂₄O₅(368.43): C 71.72, H 6.57; found: C 71.68, H 6.71.

1-(2,3-Di-O-benzyl-b-d-galactopyranosyl)-4-phenylbuta-1,3-diyne (51). A suspension of [Pd₂(dba)₃] (6 mg,

0.0125 mmol), CuI (2 mg, 0.01 mmol), P(fur)₃(6 mg, 0.0125 mmol), 50 (184 mg, 0.5 mmol), and (bromoethyn-

yl)benzene (91 mg, 0.5 mmol) in DMF (3ml) was degassed twice and stirred at 22 8 for 5 min. The mixture was

treated with Et₃N (0.3ml) and stirred for 12 h at 22 8. The soln. was diluted with Et₂O (10 ml), and treated with

H₂O (10 ml) and 0.1m aq. HCl (3ml). After separation of the layers, the aq. layer was extracted with Et ₂O (4 Â

10 ml), and the Et₂O layer was washed with H₂O (2 Â 15 ml). The combined org. fractions were dried (MgSO₄)

and evaporated. FC (cyclohexane/AcOEt 3:1) gave 51 (198 mg, 85%). R_f(cyclohexane/AcOEt 3:1) 0.47.

[a]²_D⁵ À 146.6 (c 1.1, CHCl₃). IR (CHCl₃): 3581w (br.), 3442w (br.), 3067w, 3032w, 3013m, 2928m, 2876m,

2242w, 1952w, 1881w, 1807w, 1672w, 1597w, 1554w, 1492w, 1454m, 1443w, 1367m, 1291m, 1091s, 1028m, 1013m,

985w, 914w, 884w, 83 4w. ¹H-NMR (300 MHz, CDCl₃): see Table 7; additionally, 7.75 7.72 (m, 1 arom. H); 7.53

7.48 (m, 2 arom. H); 7.45 7.40 (m, 2 arom. H); 7.40 7.30 (m, 8 arom. H); 7.19 7.15 (m, 1 arom. H); 6.58 6.54

(m, 1 arom. H); 4.98, 4.86 (2d, J 10.2, PhCH₂); 4.74 (s, PhCH₂). ¹³C-NMR (75 MHz, CDCl₃): see Table 7;

additionally, 137.68, 137.41 (2s); 132.55 (2d); 128.49 (2d); 129.33 (d); 128.33 (6d); 128.02 (d); 127.85 (d); 127.76

(2d); 121.17 (s); 75.89, 72.32 (2t, 2 PhCH₂). MALDI-MS: 491 ([M Na] ). HR-MALDI-MS: 491.1829 ([M

Na] , C₃₀H₂₈NaO₅; calc. 491.1829).

(Z)-2,6 :3,7-Dianhydro-4,5-di-O-benzyl-8-bromo-8-deoxy-l-glycero-l-galacto-oct-7-enitol (52). A suspen-

sion of 50 (92 mg, 0.25 mmol) and NBS (60 mg, 0.336 mmol) in acetone (3 ml) was treated with AgNO₃(6 mg,

0.036 mmol) and stirred for 30 min at 228. After evaporation, the residue was partitioned between H₂O and

AcOEt. The aq. layer was extracted with AcOEt (3 Â 15 ml). The combined org. fractions were washed with

brine (10 ml), dried (MgSO₄), and evaporated. FC (cyclohexane/AcOEt 4 :1) gave 52 (113mg, 93%). R_f

(cyclohexane/AcOEt 2 :1) 0.55. [a]²_D⁵ À156.2 (c 1.02, CHCl₃). IR (CHCl₃): 3594w, 3416w (br.), 3107w,

3090w, 3067w, 3031m, 3013m, 2944w, 2885m, 1664m, 1603w, 1496w, 1454m, 1363m, 1265s, 1146s, 1103s, 1038s,

1

1028s, 993m, 912w, 884w, 860w, 821w. H-NMR (300 MHz, CDCl₃): see Table 7; additionally, 7.39 7.29 (m, 10

arom. H); 4.66, 4.64 (2d, J 12.0, 2 PhCH); 4.53( d, J 12.0, 2 PhCH). ¹³C-NMR (75 MHz, CDCl₃): see

Table 7; additionally, 137.24, 137.04 (2s); 128.45 (2d); 128.42 (2d); 128.07 (d); 128.02 (2d); 127.92 (2d); 127.82 (d);

Helvetica Chimica Acta Vol. 88 (2005)

1909

71.01, 70.47 (2t, 2 PhCH₂). HR-MALDI-MS: 471.0601 (97, [M Na] , C₂₂H₂₃Na⁸¹BrO₅; calc. 471.0601),

469.0616 (100, [M Na] , C₂₂H₂₃Na⁷⁹BrO₅; calc. 469.0621).

(Z)-2,6 :3,7-Dianhydro-4,5-di-O-benzyl-8,9,10-trideoxy-10-C-phenyl-l-glycero-l-galacto-dec-7-en-9-ynitol

(53). A suspension of 51 (47 mg, 0.1 mmol) in dry MeOH (3ml) was treated with one batch of MeONa (20 mg,

0.37 mmol), kept at reflux for 10 h, and evaporated. The residue was treated with a soln. of 0.1m HCl (0.5 ml) in

H₂O (10 ml) and extracted with AcOEt (3 Â 15 ml). The combined org. fractions were washed with brine

(10 ml), dried (MgSO₄), and evaporated. FC (cyclohexane/AcOEt 4 :1) gave 53 (44 mg, 93%). R_f(cyclohexane/

AcOEt 2 :1) 0.50. [a]²_D⁵ À220.8 (c 1.05, CHCl₃). IR (CHCl₃): 3429w (br.), 3066w, 3031m, 3013m, 2929w,

2892w, 2200w, 1951w, 1879w, 1808w, 1779w, 1658m, 1596w, 1490m, 1454m, 1442w, 1381m, 1362m, 1317m, 1279m,

1171s, 1106s, 1076s, 1036m, 1028m, 996m, 928w, 914w, 876w, 844w. ¹H-NMR (300 MHz, CDCl₃): see Table 7;

additionally, 7.46 7.40 (m, 2 arom. H); 7.39 7.25 (m, 13arom. H); 4.81 ( s, irrad. at 4.24 ! NOE of 9%,

HÀC(8)); 4.67, 4.66 (2d, J 12.0, 2 PhCH); 4.54 (d, J 12.0, 2 PhCH); 4.24 (dd, J 2.1, 0.6, irrad. at 4.81 !

NOE of 14%, HÀC(6)); 3.77 (br. s, irrad. at 4.24 ! NOE of 7%, HÀC(5)). ¹³C-NMR (75 MHz, CDCl₃): see

Table 7; additionally, 137.14, 137.06 (2s); 131.37 (2d); 128.49 (2d); 128.44 (2d); 128.07 (2d); 128.04 (d); 128.00

(2d); 127.92 (d); 127.89 (2d); 127.73( d); 123.70 (s); 71.04, 70.51 (2t, 2 PhCH₂). MALDI-MS: 491 ([M Na] ).

HR-MALDI-MS: 491.1834 ([M Na] , C₃₀H₂₈NaO₅; calc. 491.1829). Anal. calc. for C₃₀H₂₈O₅(468.55): C

76.90, H 6.02; found: C 76.66, H 6.22.

(Z)-1-O-Acetyl-2,6 :3,7-dianhydro-4,5-di-O-benzyl-8,9,10-trideoxy-10-C-phenyl-l-glycero-l-galacto-dec-7-

en-9-ynitol (54). A suspension of 53 (47 mg, 0.1 mmol) in pyridine (3ml) was treated with Ac ₂O (66 ml,

0.16 mmol) and stirred overnight at 258. Co-evaporation three times with toluene and FC (cyclohexane/AcOEt

4 :1) gave 54 (49 mg, 95%). R_f(cyclohexane/AcOEt 2 :1) 0.58. IR (CHCl₃): 3107w, 3090w, 3067w, 3029m,

3014m, 2928s, 2852m, 2260w, 1952w, 1731s, 1664m, 1603w, 1496w, 1453m, 1374m, 1250s, 1146m, 1102s, 1043s,

993m, 909w, 885w, 860w, 821w. ¹H-NMR (300 MHz, CDCl₃): see Table 7; additionally, 7.46 7.41 (m, 2 arom. H);

7.39 7.25 (m, 13arom. H); 4.83( s, HÀC(8)); 4.66, 4.65 (2d, J 12.0, 2 PhCH); 4.55, 4.53(2 d, J 12.0, 2

PhCH); 2.10 (s, AcO). ¹³C-NMR (75 MHz, CDCl₃): see Table 7; additionally, 170.48 (s, CO); 137.06, 136.97

(2s); 131.33 (2d); 128.45 (2d); 128.40 (2d); 128.02 (3d); 127.95 (2d); 127.89 (d); 127.85 (2d); 127.68 (d); 123.67

(s); 71.00, 70.52 (2t, 2 PhCH₂); 20.93( q, Me).

1,6-Anhydro-4-deoxy-4-C-(4-phenylbuta-1,3-diyn-1-yl)-b-d-glucopyranose (56).

A suspension of

[Pd₂(dba)₃] (6 mg, 0.0125 mmol), CuI (2 mg, 0.01 mmol), P(fur)₃(6 mg, 0.0125 mmol), 55 [66] (85 mg,

0.5 mmol), and (bromoethynyl)benzene (91 mg, 0.5 mmol) in DMF (3ml) was degassed twice and stirred at 22 8

for 5 min. The mixture was treated with Et₃N (0.3ml) and stirred for 12 h at 22 8. The soln. was diluted with Et₂O

(10 ml), and treated with H₂O (10 ml) and 0.1m aq. HCl (3ml). The Et ₂O layer was washed with H₂O (2 Â

15 ml), and the aq. layer was extracted with Et₂O (4 Â 10 ml). The combined org. fractions were dried (MgSO₄)

and evaporated. FC (cyclohexane/AcOEt 1:1) gave 56 (102 mg, 76%). White solid. R_f(cyclohexane/AcOEt

1:1) 0.43. M.p. 128 1298. [a]²_D⁵ À41.5 (c 1.02, CHCl₃). IR (CHCl₃): 3561m, 3385w (br.), 3028w, 3014w,

2960w, 2928w, 2906w, 2855w, 2246w, 2148w, 1730w, 1597w, 1491w, 1442w, 1347w, 1297w, 1264w, 1180w, 1135m,

1111w, 1049s, 1013m, 987m, 928m, 886m, 849w, 814w. ¹H-NMR (300 MHz, CDCl₃): 7.52 7.47 (m, 2 arom. H);

7.37 7.29 (m, 3arom. H); 5.56 (br. s, HÀC(1)); 4.69 (br. d, J 4.8, HÀC(5)); 4.22 (d, J 7.8, H_endoÀC(6)); 4.07

(dquint., J 7.8, 1.5, addition of D₂O ! quint., J 1.5, HÀC(3)); 3.83 (dd, J 7.8, 5.1, H_exoÀC(6)); 3.61 (br. d,

J 11.6, addn. of D₂O ! br. s, HÀC(2)); 2.94 (br. s, HÀC(4)); 2.72 (d, J 7.8, exchanged with D₂O,

HOÀC(3)); 2.43 (d, J 11.9, exchanged with D₂O, HOÀC(2)). ¹³C-NMR (75 MHz, CDCl₃): 132.51 (2d);

129.26 (d); 128.36 (2d); 121.27 (s); 102.22 (d, C(1)); 80.59 (s, C(1')); 77.33 (s, C(4')); 75.07 (d, C(5)); 73.33 (s,

C(3')); 72.47 (d, C(3)); 70.47 (d, C(2)); 68.82 (s, C(2')); 67.38 (t, C(6)); 37.20 (d, C(4)). HR-MALDI-MS:

293.0787 ([M Na] , C₁₆H₁₄NaO₄; calc. 293.0784). Anal. calc. for C₁₆H₁₄O₄¥ 0.5 H₂O (279.28): C 68.74, H 5.37;

found: C 68.48, H 5.87.

1,6-Anhydro-4-C-(2-bromoethynyl)-4-deoxy-b-d-glucopyranose (57).

A suspension of 55 (85 mg,

0.5 mmol) and NBS (120 mg, 0.67 mmol) in acetone (5 ml) was treated with AgNO₃(12 mg, 0.072 mmol)

and stirred for 30 min at 228. After evaporation, the residue was partitioned between H₂O and AcOEt. The aq.

layer was extracted with AcOEt (3 Â 15 ml). The combined org. fractions were washed with brine (10 ml), dried

(MgSO₄), and evaporated. FC (hexane/AcOEt 1:1) gave 57 (115 mg, 92%). White solid. R_f(hexane/AcOEt

1:1) 0.56. M.p. 145 1468. [a]²_D⁵ À75.5 (c 1.01, CHCl₃). IR (CHCl₃): 3562m, 3393w (br.), 3027w, 3014w,

2961w, 2906w, 2215w, 1602w, 1476w, 1399w, 1348w, 1300w, 1182w, 1134m, 1064s, 1048s, 1008m, 986m, 929w, 884w,

851w, 817w. ¹H-NMR (300 MHz, CDCl₃): 5.53(br. s, HÀC(1)); 4.63(br. d, J 5.0, HÀC(5)); 4.18 (d, J 7.8,

H_endoÀC(6)); 4.00 (dquint., J 7.8, 1.5, addition of D₂O ! quint., J 1.5, HÀC(3)); 3.80 (dd, J 7.5, 5.1,

H_exoÀC(6)); 3.57 (br. d, J 11.5, addition of D₂O ! br. s, HÀC(2)); 2.80 (br. s, HÀC(4)); 2.67 (d, J 7.7,

exchanged with D₂O, HOÀC(3)); 2.37 (d, J 11.8, exchanged with D₂O, HOÀC(2)). ¹³C-NMR (75 MHz,

1910

Helvetica Chimica Acta Vol. 88 (2005)

CDCl₃): 102.12 (d, C(1)); 78.00 (s, C(1')); 75.02 (d, C(5)); 72.20 (d, C(3)); 70.41 (d, C(2)); 67.26 (t, C(6)); 43.46

(s, C(2')); 37.29 (d, C(4)). HR-MALDI-MS: 272.9557 (97, [M Na] , C₈H₉⁸¹BrNaO₄; calc. 272.9561), 270.9578

(100, [M Na] , C₈H₉⁷⁹BrNaO₄; calc. 270.9576). Anal. calc. for C₈H₉BrO₄(249.06): C 38.58, H 3.64; found: C

38.64, H 3.86.

X-Ray Analysis of 57⁶). Recrystallisation of 57 in Et₂O/hexane 4 :1 gave crystals suitable for X-ray

analysis: C₈H₉BrO₄(249.065); monoclinic P2₁; a 7.3149(3), b 6.8396(3), c 8.9967(3) ä, b 101.902(2)8.

V 440.44(3) ä³; Z 2; D_calc. 1.878 Mg/m³. Intensities were measured on an Enraf-Nonius CAD-4

diffractometer with MoK_aradiation (graphite monochromator, l 0.71073ä) at 298 K, q range 0.998

27.4858. Of the 1883total collected reflections, 1877 independent reflections were observed. R 0.0282, R_w

0.0862.

1,6-Anhydro-4-deoxy-4-C-(2-iodoethynyl)-b-d-glucopyranose (58). A soln. of AgNO₃(65 mg, 0.38 mmol)

and dil. NH₃/H₂O (one drop) in H₂O (3ml) was treated dropwise with a suspension of 55 (43mg, 0.25 mmol) in

acetone (3ml), stirred for 5 min, treated with NIS (90 mg, 0.4 mmol), and stirred for 30 min at 22 8 (the mixture

became clear after 5 min and then turbid again). After evaporation, the residue was partitioned between H₂O

and AcOEt. The aq. layer was extracted with AcOEt (3 Â 15 ml). The combined org. fractions were washed

with brine (10 ml), dried (MgSO₄), and evaporated. FC (cylcohexane/AcOEt 2 :1) gave 58 (64 mg, 87%). White

solid. R_f(cyclohexane/AcOEt 2 :1) 0.43. M.p. 75 768. [a]²_D⁵ À60.1 (c 1.02, CHCl₃). IR (CHCl₃): 3560m,

3401w (br.), 3027w, 3014w, 2967w, 2906w, 2253w, 1602w, 1475w, 1397w, 1348w, 1321w, 1299w, 1227w, 1182w,

1134m, 1080w, 1052m, 1046s, 1007m, 986w, 909s, 884w, 850w, 817w. ¹H-NMR (300 MHz, CDCl₃): 5.50 (br. s,

HÀC(1)); 4.62 (br. d, J 5.0, HÀC(5)); 4.15 (d, J 7.5, H_endoÀC(6)); 4.00 (br. d, J 6.9, addition of D₂O ! br.

s, HÀC(3)); 3.77 (dd, J 7.5, 5.0, H_exoÀC(6)); 3.55 (br. d, J 11.2, addition of D₂O ! br. s, HÀC(2)); 2.98 (d,

J 6.9, exchanged with D₂O, HOÀC(3)); 2.89 (br. d, J 1.9, HÀC(4)); 2.56 (d, J 11.5, exchanged with D₂O,

HOÀC(2)). ¹³C-NMR (75 MHz, CDCl₃): 102.13( d, C(1)); 92.08 (s, C(1')); 75.22 (d, C(5)); 72.41 (d, C(3));

70.52 (d, C(2)); 67.28 (t, C(6)); 38.34 (d, C(4)); 31.07 (s, C(2')). HR-ESI-MS: 318.9423 (100, [M Na] ,

C₈H₉INaO₄; calc. 318.9443). Anal. calc. for C₈H₉IO₄(296.06): C 32.46, H 3.06; found: C 32.35, H 3.15.

1,6-Anhydro-4-deoxy-4-C-(4-phenylbuta-1,3-diyn-1-yl)-b-d-erythro-hex-3-enopyranose (59). A suspension

of 56 (27 mg, 0.1 mmol) in dry MeOH (3ml) was treated with one batch of MeONa (20 mg, 0.37 mmol) and

kept at reflux for 10 h. After evaporation, the residue was treated with a soln. of 0.1m HCl (0.5 ml) in H₂O

(10 ml) and extracted with AcOEt (3 Â 15 ml). The combined org. fractions were washed with brine (10 ml),

dried (MgSO₄), and evaporated. FC (hexane/AcOEt 4 :1) gave 59 (21 mg, 82%). R_f(hexane/AcOEt 2 :1) 0.46.

[a]²_D⁵ À7.6 (c 1.0, CHCl₃). IR (CHCl₃): 3579w, 3386w (br.), 3028w, 2988w, 2928s, 2852s, 2209w, 1680w, 1598w,

1491w, 1450m, 1375m, 1360w, 1249s, 1130m, 1045m, 93 0w, 904w, 872w. ¹H-NMR (300 MHz, CDCl₃): 7.53 7.48

(m, 2 arom. H); 7.40 7.29 (m, 3arom. H); 6.23( dd, J 4.4, 1.9, HÀC(3)); 5.54 (t, J 1.6, HÀC(1)); 4.75 (d,

J 3.7, HÀC(5)); 3.81 (d, J 6.9, H_endoÀC(6)); 3.75 (dd, J 6.9, 4.0, H_exoÀC(6)); 3.74 (ddd, J 11.0, 4.5, 1.5,

addition of D₂O: dd, J 4.5, 1.5, HÀC(2)); 1.86 (d, J 11.2, exchanged with D₂O, HOÀC(2)). ¹³C-NMR

(75 MHz, CDCl₃): 133.50 (d, C(3)); 132.42 (2d); 129.50 (d); 128.39 (2d); 125.36 (s, C(4)); 121.09 (s); 101.96 (d,

C(1)); 83.55 (s, C(4')); 78.27 (s, CꢀC); 73.57 (d, C(5)); 73.09 (s, CꢀC); 69.11 (t, C(6)); 65.50 (d, C(2)); s of CꢀC

hidden by signals of CDCl₃. HR-MALDI-MS: 275.0677 ([M Na] , C₁₆H₁₂NaO₃; calc. 275.0679). Anal. calc.

for C₁₆H₁₂O₃(252.27): C 76.18, H 4.79; found: C 76.11, H 4.87.

X-Ray Analysis of 59⁶). Recrystallisation of 59 in Et₂O/hexane 4 :1 gave crystals suitable for X-ray

analysis: C₁₆H₁₂O₃(252.269); orthorhombic P2₁2₁2₁; a 7.1054(2), b 9.4375(3), c 19.4351(7) ä. V

1303.26 ä³; Z 4; D_calc. 1.286 Mg/m³. Intensities were measured on an Enraf-Nonius CAD-4 diffractometer

with MoKa radiation (graphite monochromator, l 0.71073ä) at 298 K, q range 0.998 27.4858. Of the 2937

total collected reflections, 2920 independent reflections were observed. R 0.0444, R_w 0.1298.

1,6-Anhydro-4-C-(2-bromoethenylidene)-4-deoxy-b-d-glucopyranose (60). A suspension of 57 (50 mg,

0.2 mmol) in dry MeOH (3ml) was treated with one batch of MeONa (20 mg, 0.37 mmol) and kept at reflux for

10 h. After evaporation, the residue was treated with a soln. of 0.1m HCl (0.5 ml) in H₂O (10 ml) and extracted

with AcOEt (3 Â 10 ml). The combined org. fractions were washed with brine (10 ml), dried (MgSO₄), and

evaporated. FC (hexane/AcOEt 4 :1) gave 60 (43mg, 82%). R_f(hexane/AcOEt 2 :1) 0.48. [a]²_D⁵ À47.7 (c

1.02, CHCl₃). IR (CHCl₃): 3564m, 3401w (br.), 3027m, 3015m, 2968w, 2902w, 1964w, 1730w, 1602w, 1475w,

1394w, 1347w, 1300w, 1123s, 1048s, 1009m, 976m, 946w, 93 0m, 909s, 890m, 849w, 818w. IR (KBr): 3432s (br.),

3051m, 2963m, 2926m, 2903m, 1964w, 1631w (br.), 1471w, 1432m, 1397m, 1361w, 1345m, 1309m, 1285m, 1266m,

1212w, 1150s, 1128s, 1064s, 1029s, 982m, 947s, 926s, 892s, 854s. ¹H-NMR (300 MHz, CDCl₃; 9 :1 mixture of

diastereoisomers): signals of the minor diastereoisomer: 6.27 (d, J 1.2, HÀC(2')); 5.51 (br. s, HÀC(1)); 5.02 (d,

J 4.7, HÀC(5)); 4.30 (br. d, J ꢂ 7.0, addition of D₂O ! br. s, HÀC(3)); 4.20 (d, J 7.2, H_endoÀC(6)); 3.87 (dd,

J 7.4, 4.7, H_exoÀC(6)); 3.70 (br. dq, J ꢂ 8.4, 1.5, addition of D₂O ! br. s, HÀC(2)); 2.37 (d, J 6.8, exchanged

Helvetica Chimica Acta Vol. 88 (2005)

1911

with D₂O, HOÀC(3)); 2.20 (d, J 8.7, exchanged with D₂O, HOÀC(2)); signals of the minor diastereoisomer:

6.24 (br. s, HÀC(2')); 5.05 (d, J 4.7, HÀC(5)); 4.12 (d, J 7.2, H_endoÀC(6)); 2.43( d, J 6.8, exchanged with

D₂O, HOÀC(3)); 2.26 (d, J 8.7, exchanged with D₂O, HOÀC(2)). ¹³C-NMR (75 MHz, CDCl₃; 9 :1 mixture of

diastereoisomers): signals of the major diastereoisomer: 198.59 (s, C(1')); 108.58 (s, C(4)); 102.55 (d, C(1));

75.49 (d, C(5)); 73.50 (d, C(3)); 73.08 (d, C(2')); 70.88 (t, C(6)); 69.40 (d, C(2)); signals of the minor

diastereoisomer: 73.2 (d, C(2')); 69.5 (d, C(2)). HR-MALDI-MS: 272.9555 (97, [M Na] , C₈H₉⁸¹BrNaO₄

;

calc. 272.9561), 270.9577 (100, [M Na] , C₈H₉⁷⁹BrNaO₄; calc. 270.9576).

1,6-Anhydro-4-deoxy-4-C-(2-iodoethenylidene)-b-d-glucopyranose (61). A suspension of 58 (50 mg,

0.2 mmol) in dry MeOH (3ml) was treated with one batch of t-BuOK (41 mg, 0.37 mmol) and kept at reflux

for 10 h. After evaporation, the residue was treated with a soln. of 0.1m HCl (0.5 ml) in H₂O (10 ml) and

extracted with AcOEt (3 Â 10 ml). The combined org. fractions were washed with brine (10 ml), dried

(MgSO₄), and evaporated. FC (cyclohexane/AcOEt 4 :1) gave 61 (12 mg, 68%). R_f(hexane/AcOEt 2 :1) 0.49.

[a]²_D⁵ À54.2 (c 1.05, CHCl₃). IR (CHCl₃): 3563m, 3405m (br.), 3027m, 3015m, 2963m, 2929m, 2901m, 2852w,

1955w, 1602w, 1474w, 1392m, 1345m, 1300w, 1127s, 1056s, 1000m, 975m, 945m, 93 0m, 890m, 848m. ¹H-NMR

(300 MHz, CDCl₃; 1 :1 mixture of diastereoisomers): 6.07, 6.05 (2t, J 0.8, HÀC(2')); 5.50 (br. s, HÀC(1)); 5.04,

5.02 (2 br. d, J 4.5, HÀC(5)); 4.35 4.28 (br. s, HÀC(3)); 4.18, 4.13 (2d, J 7.5, H_endoÀC(6)); 3.86, 3.83 (2dd,

J 7.5, 4.5, H_exoÀC(6)); 3.69 (br. d, J 8.0, HÀC(2)); 2.48, 2.41 (2d, J 7.1, HO ÀC(3)); 2.27, 2.23 (2d, J 8.2,

HOÀC(2)). ¹³C-NMR (75 MHz, CDCl₃; 1 :1 mixture of diastereoisomers): 201.03( s, C(1')); 102.65, 102.58 (2d,

C(1)); 102.09 (s, C(4)); 75.16, 73.36 (2d, C(5)); 72.66, 72.33 (2d, C(3)); 70.30, 70.08 (2t, C(6)); 69.62, 68.87 (2d,

C(2)); 38.97, 38.29 (2d, C(2')). HR-ESI-MS: 318.9443 (100, [M Na] , C₈H₉INaO₄; calc. 318.9443).

REFERENCES

[1] H. C. Lin, W. B. Yang, Y. F. Gu, C. Y. Chen, C. Y. Wu, C. H. Lin, Org. Lett. 2003, 5, 1087.

[2] C. F. Chang, W. B. Yang, C. C. Chang, C. H. Lin, Tetrahedron Lett. 2002, 43, 6515.

[3] P. A. Colinas, A. Lieberknecht, R. D. Bravo, Tetrahedron Lett. 2002, 43, 9065.

[4] C. Taillefumier, Y. Chapleur, Chem. Rev. 2004, 104, 263.

¬

[5] M. Gascon-Lopez, M. Motevalli, G. Paloumbis, P. Bladon, P. B. Wyatt, Tetrahedron 2003, 59, 9349.

[6] P. Molas, I. Matheu, S. Castillon, Tetrahedron Lett. 2004, 45, 3721.

¬

[7] A. M. Gomez, A. Pedregosa, A. Barrio, S. Valverde, J. C. Lopez, Tetrahedron Lett. 2004, 45, 6307.

[8] C. Taillefumier, S. Thielges, Y. Chapleur, Tetrahedron 2004, 60, 2213.

[9] E. R. H. Jones, J. S. Stephenson, J. Chem. Soc. 1959, 2197; E. R. H. Jones, J. S. Stephenson, W. B. Turner,

M. C. Whiting, J. Chem. Soc. 1963, 2048; R. C. Cambie, A. Hirschberg, E. R. H. Jones, G. Lowe, J. Chem.

Soc. 1963, 4120; E. R. H. Jones, G. Lowe, P. V. R. Shannon, J. Chem. Soc. C 1966, 139.

[10] F. Bohlmann, P. Herbst, H. Gleinig, Chem. Ber. 1961, 94, 948.

[11] D. Grandjean, P. Pale, J. Chuche, Tetrahedron Lett. 1992, 33, 4905; D. Grandjean, P. Pale, J. Chuche,

Tetrahedron Lett. 1992, 33, 5355; J. Chuche, D. Grandjean, P. Pale, Bull. Soc. Chim. Belg. 1992, 101, 415.

[12] M. Yoshimatsu, M. Naito, H. Shimizu, O. Muraoka, G. Tanabe, T. Kataoka, J. Org. Chem. 1996, 61, 8200.

[13] P. Timmerman, L. E. Witschel, F. Diederich, C. Boudon, J. P. Gisselbrecht, M. Gross, Helv. Chim. Acta

1996, 79, 6.

[14] V. Dalla, P. Pale, New J. Chem. 1999, 23, 803; P. Pale, J. Chuche, Eur. J. Org. Chem. 2000, 1019.

[15] F. E. McDonald, C. B. Connolly, M. M. Gleason, T. B. Towne, K. D. Treiber, J. Org. Chem. 1993, 58, 6952;

F. E. McDonald, C. C. Schultz, J. Am. Chem. Soc. 1994, 116, 9363; F. E. McDonald, M. M. Gleason, J. Am.

Chem. Soc. 1996, 118, 6648.

[16] B. M. Trost, Y. H. Rhee, J. Am. Chem. Soc. 2002, 124, 2528.

[17] B. M. Trost, Y. H. Rhee, J. Am. Chem. Soc. 2003, 125, 7482; B. M. Trost, Y. H. Rhee, Org. Lett. 2004, 6, 4311.

[18] P. Wipf, T. H. Graham, J. Org. Chem. 2003, 68, 8798.

[19] F. E. McDonald, K. S. Reddy, Y. Diaz, J. Am. Chem. Soc. 2000, 122, 4304; F. E. McDonald, K. S. Reddy,

Angew. Chem., Int. Ed. 2001, 40, 3653; F. E. McDonald, K. S. Reddy, J. Organomet. Chem. 2001, 617 618,

¬

444; F. E. McDonald, M. L. Wu, Org. Lett. 2002, 4, 3979; E. Alcazar, J. M. Pletcher, F. E. McDonald, Org.

Lett. 2004, 6, 3877.

[20] M. D. Weingarten, A. Padwa, Tetrahedron Lett. 1995, 36, 4717; A. Padwa, K. E. Krumpe, M. D.

Weingarten, J. Org. Chem. 1995, 60, 5595.

¬

[21] F. J. Reboredo, M. Treus, J. C. Estevez, L. Castedo, R. J. Estevez, Synlett 2002, 999.

[22] J. Stichler-Bonaparte, B. Bernet, A. Vasella, Helv. Chim. Acta 2002, 85, 2235.

1912

Helvetica Chimica Acta Vol. 88 (2005)

[23] T. V. Bohner, O.-S. Becker, A. Vasella, Helv. Chim. Acta 1999, 82, 198.

[24] R. B¸rli, A. Vasella, Helv. Chim. Acta 1997, 80, 2215.

[25] A. Vasella, Pure Appl. Chem. 1998, 70, 425.

[26] B. Bernet, A. Vasella, in −Acetylene Chemistry. Chemistry, Biology, and Material Science×, Eds. F.

Diederich, P. J. Stang, R. R. Tykwinski, Wiley-VCH, Weinhein, 2004, p. 173 321.

[27] M. J. S. Dewar, E. G. Zoebisch, E. F. Healy, J. J. P. Stewart, J. Am. Chem. Soc. 1985, 107, 3902.

[28] J. J. P. Stewart, J. Comput. Chem. 1989, 10, 209.

[29] Semichem, −AMPAC 6.0×, 7128 Summit, Shawnee, KS 66216, 1998.

[30] B. Hoffmann, D. Zanini, I. Ripoche, R. B¸rli, A. Vasella, Helv. Chim. Acta 2001, 84, 1862.

[31] B. Hoffmann, B. Bernet, A. Vasella, Helv. Chim. Acta 2002, 85, 265.

¬

[32] P. R. Muddasani, E. Bozo, B. Bernet, A. Vasella, Helv. Chim. Acta 1994, 77, 257.

[33] B. Bernet, A. Vasella, Helv. Chim. Acta 2000, 83, 995.

[34] F. Mohamadi, N. G. J. Richards, W. C. Guida, R. Liskamp, C. Caufield, M. Lipton, G. Chang, T.

Hendrickson, W. C. Still, J. Comput. Chem. 1990, 11, 440.

[35] M. D. Banciu, M. D. Stanescu, C. Florea, A. Petride, C. Draghici, E. Cioranescu, Bull. Soc. Chim. Fr. 1991,

919.

[36] H.-J. Liu, W.-L. Yeh, E. N. C. Browne, Can. J. Chem.-Rev. Can. Chim. 1995, 73, 1135.

[37] J. I. Musher, E. J. Corey, Tetrahedron 1962, 18, 791.

[38] C. M. Evans, A. J. Kirby, J. Chem. Soc., Perkin Trans. 2 1984, 1269.

[39] J. M. J. Tronchet, A. P. Bonenfant, F. Perret, A. Gonzalez, J. B. Zumwald, E. M. Martinez, B. Baehler, Helv.

Chim. Acta 1980, 63, 1181.

[40] J. M. Aurrecoechea, B. Lopez, M. Arrate, J. Org. Chem. 2000, 65, 6493.

[41] H. Hofmeister, K. Annen, H. Laurent, R. Wiechert, Angew. Chem., Int. Ed. 1984, 23, 727.

[42] M. J. Robins, S. F. Wnuk, X. D. Yang, C. S. Yuan, R. T. Borchardt, J. Balzarini, E. De Clercq, J. Med. Chem.

1998, 41, 3857.

[43] N. N. Sveshnikov, V. I. Nikulin, Magn. Reson. Chem. 1995, 33, 755.

[44] A. Ernst, A. Vasella, Helv. Chim. Acta 1996, 79, 1279.

[45] V. M. S. Gil, W. von Philipsborn, Magn. Reson. Chem. 1989, 27, 409.

[46] D. Beer, A. Vasella, Helv. Chim. Acta 1985, 68, 2254.

[47] S. Fritschi, A. Vasella, Helv. Chim. Acta 1991, 74, 2024.

[48] S. E. Mangholz, A. Vasella, Helv. Chim. Acta 1995, 78, 1020.

[49] G. Pairaudeau, P. J. Parsons, J. M. Underwood, J. Chem. Soc., Chem. Commun. 1987, 1718.

[50] S. Takano, Y. Iwabuchi, K. Ogasawara, J. Chem. Soc., Chem. Commun. 1989, 1371.

[51] C. Mukai, H. Yamashita, M. Hanaoka, Org. Lett. 2001, 3, 3385.

[52] V. K. Brel, Synthesis 2001, 1539.

[53] G. Bendz, Ark. Kemi 1959, 14, 475; G. Bendz, Ark. Kemi 1960, 15, 13 1.

[54] R. E. Bew, J. R. Chapman, E. R. H. Jones, B. E. Lowe, G. Lowe, J. Chem. Soc. C 1966, 129.

[55] L. I. Olsson, A. Claesson, Synthesis 1979, 743.

¬

[56] J. Grimaldi, A. Cormons, C. R. Hebd. Seances Acad. Sci., Ser. C 1979, 289, 373.

[57] J.-J. Chilot, A. Doutheau, J. Gore, Tetrahedron Lett. 1982, 23, 4693; J.-J. Chilot, A. Doutheau, J. Gore, Bull.

Soc. Chim. Fr., Part. II 1984, 307.

[58] A. Jellal, J. Grimaldi, M. Santelli, Tetrahedron Lett. 1984, 25, 3179.

[59] H. Ohno, H. Hamaguchi, M. Ohata, T. Tanaka, Angew. Chem., Int. Ed. 2003, 42, 1749.

[60] V. G. Andreev, A. F. Kolomiets, A. V. Fokin, Bull. Acad. Sci. USSR, Div. Chem. Sci. 1991, 40, 2447.

[61] R. Paul, S. Tchelitcheff, Compt. Rend. 1950, 230, 1872.

[62] G. Eglinton, E. R. H. Jones, M. C. Whiting, J. Chem. Soc. 1952, 2873.

[63] V. A. Olah, A. Liptak, J. Harangi, P. Nanasi, Acta Chim. Hung. 1985, 118, 25.

[64] W. Yuan, S. A. Babirad, Y. Kishi, J. Org. Chem. 1992, 57, 468.

[65] E. A. Larsson, J. Ulicny, A. Laaksonen, G. Widmalm, Org. Lett. 2002, 4, 1831.

[66] J. Alzeer, C. Cai, A. Vasella, Helv. Chim. Acta 1995, 78, 242.

[67] P. Uhlmann, A. Vasella, Helv. Chim. Acta 1992, 75, 1979.

[68] M. Brossi, C. Ganter, Helv. Chim. Acta 1988, 71, 848; M. Brossi, C. Ganter, Helv. Chim. Acta 1987, 70, 1963.

[69] H. Westmijze, H. Kleijn, H. J. T. Bos, P. Vermeer, J. Organomet. Chem. 1980, 199, 293.

Received March 8, 2005

Article Doi

Functionalised bicyclic exo-glycals by alkynol cycloisomerisation of hydroxy 1,3-diynes and hydroxy haloalkynes

DOI: 10.1002/hlca.200590145

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