Diastereo‐ and Enantioselective Synthesis of Bisbenzannulated Spiroketals and Spiroaminals by Ir/Ag/Acid Ternary Catalysis

Abstract

We reported herein an iridium/silver/acid ternary catalytic system to access bisbenzannulated [6,6]-spiroketals in high efficiency with generally high diastereo-and enantioselectivities (up to > 20 : 1 dr, > 99 % ee). In this procedure, readily available o-alkynylacetophenones undergo cycloisomerization to generate isochromenes in situ that participate in stereoselective allylation/spiroketalization sequence with 2-(1-hydroxyallyl)phenols. Meanwhile, 2-(1-hydroxyallyl)anilines were also compatible in this cascade reaction, furnishing structurally novel bisbenzannulated [6,6]-spiroaminals with good diastereoselectivities (8 : 1-12 : 1 dr) and excellent enantioselectivities (98 %-> 99 % ee). Moreover, experimental studies and theoretical calculations were performed to illustrate the reaction mechanism and stereochemistry.

Exploiting the reactivities ofortho-alkynyl aryl ketones: opportunities in designing catalytic annulation reactions

“…The asymmetric reaction resulted in a series of dibenzannulated [6,6]-spiroketals and [6,6]-spiroaminals 82 in 35-92% yields, 1.2 : 1->20 : 1 dr. and 88->99% ee (Scheme 33). 71 Many different substituents such as methyl, methoxy, t-butyl, ester, halo and thiazole groups on the phenyl ring of starting substrates could all tolerate this ternary catalytic system. All these results demonstrated a wide substrate scope for this asymmetric ternary catalytic methodology.…”

Advances in Catalytic Asymmetric Reactions Involving o-Hydroxybenzyl Alcohols

“…过渡金属 催化的偶极体及前体参与的不对称环加成反应近年来 发展得十分迅速, 逐渐成为构建手性螺环化合物的重要 策略 [30] . 2022 年, 邓卫平课题组 [31] 同年, 邓卫平课题组 [32]…”

“…Catalytic asymmetric addition reaction of o-hydroxybenzyl alcohols with enamines [32,40,44] . 所以, 很有必要探究邻羟基 苄醇参与催化不对称反应的反应性和立体选择性的理 论根源, 解释并推测邻羟基苄醇参与的催化不对称反应 的活化模式和可能的过渡态, 为邻羟基苄醇参与的新型 反应的设计与开发奠定理论基础; (5)虽然邻羟基苄醇参 与的催化不对称反应为合成结构多样的手性含氧杂环 化合物及芳基甲烷化合物提供了高效的方法, 但是目前 针对这些产物的应用性研究非常有限, 仅有一些研究工 作涉及到这些手性化合物在天然产物合成 [22,31] 、生物活…”

Catalytic Asymmetric [3 + 2] Cycloaddition of Exocyclic Enol Ethers for the Synthesis of Spiroketals

“…23,24 Recently, the Deng group also demonstrated that the exocyclic enol ethers were excellent synthons for the synthesis of chiral spiroketals via asymmetric [4 + 2] cycloaddition (Scheme 1b, path v). 25,26 On the other hand, 1,4-quinones are considered as useful building blocks for construction of oxygen-containing heterocyclic compounds, 27−31 and the related catalytic asymmetric applications in organic synthesis are thriving. 32−36 continuation of our interest in asymmetric transformations of 1,4-quinone, 37,38 we envisioned the possibility of a chiral Lewis-acid-promoted intermolecular cycloaddition of exocyclic enol ethers with 1,4-quinones to establish benzannulated spiroketals.…”

“…Yeung and Tse innovatively developed an organocatalitic enantio- and diastereoselective domino halocyclization and spiroketalization of olefinic keto-acids with a halogen source through a dynamic–kinetic resolution process of the key lactol intermediate (path iv) . Our group reported an asymmetric cycloisomerization/[4 + 2] cyclization cascade reaction of keto esters with alkynyl alcohols or β-alkynyl ketones by employing a bimetallic relay catalytic system, wherein the key exocyclic enol ether intermediates were involved (path v). , Recently, the Deng group also demonstrated that the exocyclic enol ethers were excellent synthons for the synthesis of chiral spiroketals via asymmetric [4 + 2] cycloaddition (Scheme b, path v). , …”