TY - JOUR
T1 - Azidation of Partially Protected Carbohydrate Derivatives
T2 - Efficient Suppression of Acyl Migration
AU - Stepanova, Elena V.
AU - Zinin, Alexander I.
AU - Abronina, Polina I.
AU - Chizhov, Alexander O.
AU - Kononov, Leonid O.
PY - 2020/9/16
Y1 - 2020/9/16
N2 - Although azidation by nucleophilic substitution is widely used in organic chemistry, it has a limitation for partially protected carbohydrate derivatives under typical reaction conditions used for azidation (heating with NaN 3, phase-transfer catalyst (optional), DMF or DMSO) as it can cause substantial migration (70%) of O -acyl protective groups. Several approaches, including the use of a temporary protective group for the unprotected hydroxyl group, to avoid acyl migration have been compared. Addition of excess of ethyl trifluroacetate effectively suppressed benzoyl migration but inhibited substitution of the chlorine atom with the azido group. The most robust procedure involved addition of excess n -butyl formate to the reaction mixture. When this protocol was followed, migration of benzoyl groups in lactose derivatives with free hydroxy group at C-3′ or C-4′ was reduced to 4%, with the yield of the target, partially protected derivatives with an azido group in the aglycone approaching 92%.
AB - Although azidation by nucleophilic substitution is widely used in organic chemistry, it has a limitation for partially protected carbohydrate derivatives under typical reaction conditions used for azidation (heating with NaN 3, phase-transfer catalyst (optional), DMF or DMSO) as it can cause substantial migration (70%) of O -acyl protective groups. Several approaches, including the use of a temporary protective group for the unprotected hydroxyl group, to avoid acyl migration have been compared. Addition of excess of ethyl trifluroacetate effectively suppressed benzoyl migration but inhibited substitution of the chlorine atom with the azido group. The most robust procedure involved addition of excess n -butyl formate to the reaction mixture. When this protocol was followed, migration of benzoyl groups in lactose derivatives with free hydroxy group at C-3′ or C-4′ was reduced to 4%, with the yield of the target, partially protected derivatives with an azido group in the aglycone approaching 92%.
KW - azide
KW - carbohydrate
KW - protecting group
KW - regioselectivity
UR - http://www.scopus.com/inward/record.url?scp=85091037039&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85091037039&partnerID=8YFLogxK
U2 - 10.1055/s-0040-1707137
DO - 10.1055/s-0040-1707137
M3 - Article
AN - SCOPUS:85091037039
VL - 31
SP - 1491
EP - 1496
JO - Synlett
JF - Synlett
SN - 0936-5214
IS - 15
ER -