Trichloroacetimidate

Trichloroacetimidate refers to a class of organic imidates in which an alkoxy substituent is bound to a carbon that also bears a trichloroacetyl imidate moiety. In practice, the most important members are glycosyl trichloroacetimidates, formed from protected sugars and trichloroacetimidoyl chloride. These donors feature a leaving group on the anomeric position that can be activated under mild conditions to generate an oxocarbenium ion, enabling glycosylation with a wide range of alcohol acceptors.

Preparation of trichloroacetimidates typically involves condensation of an alcohol with trichloroacetimidoyl chloride in the presence of a base. For carbohydrates, this means converting a protected sugar hemiacetal into the corresponding glycosyl trichloroacetimidate. The resulting donors are generally stable to air and moisture when stored properly and can be isolated as crystalline solids or liquids.

Activation and use in glycosylation are the primary applications. Under catalytic amounts of Lewis or Brønsted acids such as TMSOTf or BF3·Et2O, the trichloroacetimidate donor is activated to form an oxocarbenium ion, which reacts with an alcohol acceptor to give a glycosidic bond. This approach, known as Schmidt glycosylation, is valued for mild conditions, broad substrate scope, and controllable stereoselectivity through protecting-group effects and reaction parameters.

In summary, trichloroacetimidates, especially glycosyl donors, are key reagents in carbohydrate synthesis, offering a versatile, relatively mild glycosylation strategy with tunable reactivity and selectivity. They were popularized in glycoscience by the Schmidt method.

See also: acetimidate donors, Schmidt glycosylation, glycosylation.