Rh‐Catalyzed CC Cleavage of Benzyl/Allylic Alcohols to Produce Benzyl/Allylic Amines or other Alcohols by Nucleophilic Addition of Intermediate Rhodacycles to Aldehydes and Imines

Abstract

We report three transformations: 1) direct transformation from biarylmethanols into biarylmethylamines; 2) direct transformation from one biarylmethanol into another biarylmethanol; 3) direct transformation from allylic alcohols into allylic amines. These transformations are based on pyridyl‐directed Rh‐catalyzed CC bond cleavage of secondary alcohols and subsequent addition to CX (X=N or O) double bonds. The reaction conditions are simple and no additive is required. The driving force of CC bond cleavage is the formation of the stable rhodacycle intermediate. Other directing groups, such as the pyrazolyl group, can also be used although it is not as efficient as the pyridyl group. We carried out in‐depth investigations for transformation 1 and found that: 1) the substrate scope was broad and electron‐rich alcohols and electron‐deficient imines are more efficient; 2) as the leaving group, aldehyde had no significant impact on either the CC bond cleavage or the whole transformation; 3) mechanistic studies (intermediate isolation, in situ NMR spectroscopic studies, competing reactions, isotopic labeling experiments) implied that: i) The CC cleavage was very efficient under these conditions; ii) there is an equilibrium between the rhodacycle intermediate and the protonated byproduct phenylpyridine; iii) the addition step of the rhodacycle intermediate to imines was slower than the CC cleavage and the equilibrium between the rhodacycle and phenylpyridine; iv) the whole transformation was a combination of two sequences of CC cleavage/nucleophilic addition and CC cleavage/protonation/CH activation/nucleophilic addition, with the latter being perhaps the main pathway. We also demonstrated the first example of cleavage of an C(alkenyl)C(benzyl) bond. These transformations showed the exchange (or substitution) of the alcohol group with either an amine or another alcohol group. Like the “group transplant”, this method offers a new concept that can be used to directly synthesize the desired products from other chemicals through reorganization of carbon skeletons.

Rhodium-catalyzed inert chemical bonds transformation and related mechanism investigation

“…经过推理 分析, 该 Rh(III)物种也可以通过 Rh(I)对 C-H 键进行 氧化加成得到(图 1(b)), 通过 Rh(III)对 C-C 键进行 -C 消除得到(图 1(c)), 或通过 Rh(I)对 C-C 键进行氧 化加成得到(图 1(d)). 以此为基础, 我们开展了通过 C-H 键活化进行的脱羰基偶联反应 [10] 以及通过 C-C 键断裂进行的烯基化 [11] 、芳基化 [12] 、还原断裂 [13] 、 有 机分子片段转换 [14] 、脱羰基化 [15] 以及有机片段的快 速重组反应 [16] . 本文以这些工作为素材, 展示利用几 种重要的物理有机手段, 如同位素(氢元素、碳元素) 实验、竞争反应、活性中间体合成、动力学实验和计 算化学在反应机理研究中的应用.…”

“…在此, 通过 C-H 键对亚胺类化合物 的加成反应为例进行说明(反应方程式见图 3) [3] . 首 先, 合成了可能的关键中间体五元环金属 Rh 物种 1, 如图 9 所示 [4] , [13] 以及有机分子片段 转移反应 [14] 中的关键活性中间体(图 11) [13,14] . [13] , 如通过产生二苯基吡啶类化合物的速度大于生成醇 类化合物的速度推断 Rh(III)物种不可能同时催化 C-C 键的断裂和醛类化合物的还原, 从而支持了我 们反应中提出的 Rh(III)物种先催化 C-C 键断裂, 再 催化醛类化合物还原成醇的反应机理.…”

“…在本研究组 [14] 对于 C-C 键断裂进行有机分子片 段转化过程的研究中(图 13, 反应方程式见图 11), 通 过动力学曲线观察到原料醇化合物急剧减少同时伴 有大量的 2-苯基吡啶生成, 1.5 h 后, 原料醇全部转换, 同时有约 10%的产物生成. 随着反应时间延长, 2-苯 图 12 动力学曲线在 C-C 键还原断裂中的应用 [13] 图 13 动力学曲线在有机分子片段转化中的应用 [14] 基吡啶的浓度减少反应物浓度增大.…”

“…在本研究组 [14] 对于 C-C 键断裂进行有机分子片 段转化过程的研究中(图 13, 反应方程式见图 11), 通 过动力学曲线观察到原料醇化合物急剧减少同时伴 有大量的 2-苯基吡啶生成, 1.5 h 后, 原料醇全部转换, 同时有约 10%的产物生成. 随着反应时间延长, 2-苯 图 12 动力学曲线在 C-C 键还原断裂中的应用 [13] 图 13 动力学曲线在有机分子片段转化中的应用 [14] 基吡啶的浓度减少反应物浓度增大. 通过这些信息 可以得出, 在此反应过程中 C-C 键的断裂非常迅速; 在环 Rh 物种和 2-苯基吡啶中有一个平衡, 环 Rh 物 种对亚胺的加成速率比 C-C 断裂的速率以及环 Rh 物 种转换为 2-苯基物种的速率慢; 反应以 C-C 键断裂/ 质子化后再进行 C-C 键活化的过程为主, 同时也存 在通过 C-C 键断裂直接进行加成反应的过程.…”

Palladium‐Catalyzed Cross‐Coupling of Furfuryl Alcohols with Arylboronic Acids via Aromatization‐Driven Carbon−Carbon Bond Cleavage to Synthesize 5‐Arylfurfuryl Alcohols and 2,5‐Diaryl Furans

“…In contrast, there have been only a few examples of direct catalytic C−C bond cleavage reactions of primary alcohols, because oxidation of the hydroxyl groups of such compounds to aldehydes occurs more readily than C−C bond cleavage. However, Shi and co‐workers reported two examples of C−C bond cleavage reactions of primary alcohols, albeit with low yields . In addition, aromatization has proved to be a driving force for C−C bond cleavage, but only a few examples have been reported .…”