Studies of Catalyst-Controlled Regioselective Acetalization and Its Application to Single-Pot Synthesis of Differentially Protected Saccharides.
Studies of Catalyst-Controlled Regioselective Acetalization and Its Application to Single-Pot Synthesis of Differentially Protected Saccharides.
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DOI：
10.1021/jacs.1c08448
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发表时间：
2021-11-10
影响因子：
15
通讯作者：
Nagorny P
中科院分区：
文献类型：
--
作者：
Wang S;Zhelavskyi O;Lee J;Argüelles AJ;Khomutnyk YY;Mensah E;Guo H;Hourani R;Zimmerman PM;Nagorny P
本文以手性磷酸（CPAs）及其固定化聚合物变体(R)-Ad-TRIP-PS和(S)-SPINOL-PS为催化剂，研究了单糖基二醇的区域选择性缩醛保护。这些由催化剂控制的区域选择性缩醛反应对各种d -葡萄糖、d -半乳糖、d -甘露糖和L-聚焦衍生的1,2-二醇具有高的区域选择性（高达25:1 rr），并且可以根据手性催化剂的选择以区域发散的方式进行。聚合物催化剂可方便地回收和多次重复使用，催化负荷低至0.1 mol%，并且其性能通常优于其单体变体的性能。这些区域选择性羧酸催化的缩醛化反应成功地与常见的羟基功能化反应结合在一起，形成了32个区域异构纯差异保护的单糖和双糖衍生物。为了进一步证明聚合物催化剂的实用性，将同一批(R)-Ad-TRIP-PS催化剂回收再利用，完成了6种差异保护d-葡萄糖衍生物的单锅克级合成。随后利用核磁共振对氘化和非氘化底物的反应机理进行了探索，发现低温缩醛反应是通过同构加成机制发生的，并且反应的区域选择性对温度有很强的依赖性。计算研究表明，复杂的温度依赖于两种反应机制的相互作用，一种涉及到一个异构磷酸盐中间体，另一种通过协调的异步形成缩醛，导致同步加成产物。计算模型还解释了导致所观察到的c2选择性的空间因素，并与实验观察到的选择性趋势相一致。
This article describes the studies on regioselective acetal protection of monosaccharide-based diols using chiral phosphoric acids (CPAs) and their immobilized polymeric variants, (R)-Ad-TRIP-PS and (S)-SPINOL-PS as the catalysts. These catalyst-controlled regioselective acetalizations were found to proceed with high regioselectivities (up to >25:1 rr) on various D-glucose, D-galactose, D-mannose and L-fucose derived 1,2-diols, and could be carried in a regiodivergent fashion depending on the choice of the chiral catalyst. The polymeric catalysts were conveniently recycled and reused multiple times for gram scale functionalizations with catalytic loading as low as 0.1 mol%, and their performance was often found to be superior to the performance of their monomeric variants. These regioselective CPA-catalyzed acetalizations were successfully combined with common hydroxyl group functionalizations as single-pot telescoped procedures to produce 32 regioisomerically pure differentially protected mono- and disaccharide derivatives. To further demonstrate the utility of the polymeric catalysts, the same batch of (R)-Ad-TRIP-PS catalyst was recycled and reused to accomplish single-pot gram-scale syntheses of 6 differentially protected D-glucose derivatives. The subsequent exploration of the reaction mechanism using NMR studies of deuterated and nondeuterated substrates revealed that low-temperature acetalizations happen via a syn-addition mechanism, and that the reaction regioselectivity exhibits strong dependence on the temperature. The computational studies indicate complex temperature-dependent interplay of two reaction mechanisms, one involving an anomeric phosphate intermediate and another via concerted asynchronous formation of acetal that results in syn-addition products. The computational models also explain the steric factors responsible for the observed C2-selectivities and are consistent with experimentally observed selectivity trends.
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影响因子：
4.3
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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