FREE-RADICAL THIOL-ENE AND THIOL-YNE COUPLINGS AS CLICK PROCESSES FOR GLYCOCONJUGATION - Click Chemistry in Glycoscience: New Developments and Strategies - page 47

AcO

OAc

O

AcO

OAc

OAc OAc AcO

AcO

O

AcO S O OAc

O

OAc

O Ac AcO l

DPAP (0.6 eq.)
EtOH, 1 h

max 365 nm

AcO
AcO

S O

AcO
AcO

SH OAc

+ +

AcO

AcO OAc

15 1 1 6 1

80% (dr 57:43)

(6 eq.)

SCHEME 3.4 TEC between a sugar thiol and a glycal.

(2 mL) was added DPAP (3.1 mg, 0.012 mmol). The solution was irradiated at room
temperature for 15 minutes under magnetic stirring, then concentrated. The pale
yellow residue was eluted from a column of silica gel with 1:1 cyclohexane-AcOEt
to give 6 (59 mg, 89%) as a white solid; [ 113.0 ( c 1.3, CHCl 3 ).

Another TEC-based approach to S -linked disaccharides entailed the coupling
of glycosyl thiols with glycals [16]. TEC is currently carried out on terminal
alkenes whereas in this case the challenge laid in performing the reaction on an
endocyclic carbon-carbon double bond. Only the free-radical addition of thioacetic
acid to D-glucal was previously reported in 1970 [17]. This reaction was scarcely
stereoselective as it afforded a mixture of two diastereomeric thioacetates, that is, one
with the AcS group axial and the other with the AcS group equatorial, in 70:30 ratio.
Thus, it was not surprising that the photoinduced reaction (

] D =+

max 365 nm) between
D-glucal triacetate 15 and peracetylated glucosyl thiol 1 (6 eq.) in the presence of
DPAP produced the S -disaccharide diastereomers 16 and 17 in 57:43 ratio and 80%
isolated overall yield (Scheme 3.4). Hence, the reaction was essentially lacking
in diastereoselectivity while it appeared to be totally regioselective with the thiyl
radical attacking exclusively the C2 of glucal.
It was suggested that the reaction proceeded through the formation of two anomeric
glycosyl radical (AGR) intermediates stabilized by the adjacent oxygen atom, namely
AGR 1 19 in which the RS group (R sugar) is axial and AGR 2 20 in which the

same group is equatorial (Scheme 3.5). In the present case these intermediates should

=

OAc

O

Ac AcO

SH

AcO
1

OAc

AcO

OAc

16

AcO S O O

OAc

OAc

Ac AcO

.

O

. Ac AcO

S

OAc 19

AcO
18

O

AcO
AcO

OAc

15

O

AcO
AcO

AcO

SH

O

AcO
AcO

AcO
1

.

OAc

S

O 17

OAc

AcO

OAc

20

SCHEME 3.5 Stereochemistry of the addition of thiyl radical 18 to D-glucal 15 .