Stereoelectronic Control in Regioselective Carbohydrate Protection

Abstract

Organotin-mediated regioselective protection has been extensively used in organic synthesis for many years. However, the mechanistic origin of the resulting regioselectivity is still not clear. By the comparison of the steric and stereoelectronic effects controlling the geometry of five-membered rings formed from neighboring group participation, from intramolecular acyl group migration, or from orthoester transesterification on pyranoside rings, a theory on the pattern resulting from the reaction with dibutyltin oxide is presented. It is thus suggested that the regioselectivity of organotin-mediated protection is controlled by analogous steric and stereoelectronic effects as in neighboring group participation and acyl group migration, mainly dependent on the stereoelectronic effects of the pyranoside itself, and not related to complex stannylene structures. An organotin protection mechanism is also suggested, emanating from steric and stereoelectronic effects, nucleophilicity, and organotin acyl migration.

Regioselective Benzoylation of Diols and Carbohydrates by Catalytic Amounts of Organobase

“…More specifically, developing environment-friendly, convenient, efficient and highly regioselective carbohydrate protection methods remains as one of the most prominent challenges [9]. Over the last several decades, many protection methods have been developed, including the use of reagents such as organotin [10][11][12], organoboron [13,14], organosilicon [15][16][17], metal salts [18][19][20][21][22][23], organobase [24][25][26], and enzymes [27][28][29][30]. Although these reagents each have advantages, they also possess troublesome shortcomings including inherent toxicity, high cost and the necessity to pre-protect secondary hydroxyl groups.…”

An Iron(III) Catalyst with Unusually Broad Substrate Scope in Regioselective Alkylation of Diols and Polyols

“…This conception is likely to have held back the development of other reagents used in selective protection because it is difficult to identify structures that can form analogous dimer or polymer structures. In 2012, after comparisons of the product patterns of three fundamentally different reactions—neighboring group participation, acyl group migration, and organotin‐mediated protection—we could, however, propose that the regioselectivities achieved by organotin compounds were not related to complex stannylene structures, but instead resulted from the stereoelectronic effects of the substrates themselves . It was thus predicted that analogous selectivities could be obtained if the organotin reagents were replaced by reagents that could form cyclic dioxolane‐type intermediates with hydroxyl groups.…”

Design and synthesis of benzyl 4-O-lauroyl-α-L-rhamnopyranoside derivatives as antimicrobial agents

“…Our present research work mainly describes the synthesis of benzyl 4-O-lauroyl--Lrhamnopyranoside (7) with its 2,3-di-O-acyl derivatives (8)(9)(10) and antimicrobial evaluation/studies of all the synthesized products.…”

“…To get new biologicaly active derivatives of L-rhamnose three 2,3-di-O-acyl derivatives (8)(9)(10) containing various groups (e.g. acetyl, mesyl and benzoyl) (Scheme 2), were prepared.…”

“…However, desired protection pattern can be achieved in one or few steps making use of complex reaction sequences. 10 For example, organotin reagents, such as tributyltin oxide or dibutyltin oxide [11][12] are often used to accomplish regioselective protection, including acylation [13][14] of hydroxyl group of carbohydrate derivatives. Typically, the regioselectivity is difficult to control due to the similarity of the secondary 2, 3 and 4-trihydroxyls of rhamnose.…”