Synthesis and applications of masked oxo-sulfinamides in asymmetric synthesis

Abstract

This short perspective reports on the synthesis and applications of a class of chiral amino carbonyl compounds, masked oxo-sulfinamides where the amine is protected with an N-sulfinyl moiety and the carbonyl group is protected as the ketal or 1,3-dithiane. These polyfunctionalized chiral building blocks are prepared by addition of organometallic reagents to masked oxo-sulfinimines (N-sulfinyl imines) or the addition of oxo-organometallic reagents and lithio-1,3-dithianes to sulfinimines. Because unmasking of the amino and carbonyl groups results in cyclic imines, these chiral building blocks are particularly useful for the asymmetric synthesis of functionalized nitrogen heterocycles, including prolines, pipecolic acids, pyrrolidines, homotropinones, tropinones, and tropane alkaloids such as cocaine and C-1 cocaine analogues.

Diastereoselective Synthesis and Characterization of Homoallylic <i>N</i>-<i>tert</i>-Butanesulfinyl Amines: An Asymmetric Synthesis Experiment for the Undergraduate Organic Laboratory

“…立体化学是有机化学教学中的一个重要概念，与之相关的手性、不对称合成等在生命科学、药 物、材料等学科中均有着极其重要的应用。由于涉及的概念抽象，特别是不对称合成涉及的对映选 择性、非对映选择性等多种概念，传统的理论教学虽能在一定程度上帮助学生理解立体化学中的诸 多概念，但对于初学者来说，这些概念可能比较抽象，难以产生直观的体会。学生经常会见到同时 出现对映异构体和非对映异构体的反应，但往往很难明确指出两者的异同。为了解决这一问题，不 妨利用教学实验让学生对立体化学产生直观而明确的印象。在建设"双一流"高校和"双一流"学 科的过程当中，实验的设计更应符合学生的知识水平，更应适合本科阶段人才培养的要求，更应为 学生之后的科研学习铺平道路。因此，本科教学迫切地需要一个合适的实验，帮助本科生理解非对 映异构体，产物 dr 值等概念。 由于教学实验受限于有限的时间、有限的规模和条件，以及对实验内容安全性、可操作性等的 要求，开发此类实验还是有一些挑战和困难。目前，在不对称合成领域，科学家已经报道了非常多 的优秀的不对称合成的方法，但是不可否认的是，很多不对称合成反应或耗时较长，或所需温度苛 刻，或选择性过高或过低导致缺乏具有演示性的教学意义。因此，需要一个简单高效的实验，同时 清晰地阐述对映异构体和非对映异构体。通过手性助剂参与的不对称合成，通过底物诱导产生非对 映选择性，清除辅基后便可得到对映体富集的产物，这类反应除了具有较高的非对映选择性，与其 相关的研究往往比较透彻，对其反应机理的了解也比较深入 [1] 。在众多手性助剂中 [2][3][4][5][6] ，Evans 助剂 已被两所学校的本科有机化学实验室用于示范实验 [7,8] 。这些实验不仅覆盖了有机化学中的许多重要 方向，同时强调了手性助剂在引入非对映选择性时的作用。尽管如此，现有的化学教育文献中，仍 然缺少对不对称合成的深入探索，如反应机理、立体化学概念等方面。显而易见，本科实验教学仍 然需要一个包含了这些基本概念(非对映异构体、dr 值等)以及相应表征方法的演示实验。基于 Davis [9][10][11] 和 Ellman [12][13][14] 等在亚磺酰亚胺合成与应用上的进展，人们对锌参与的 N-叔丁基亚磺酰亚 胺的烯丙基化反应开发了多种反应条件的实验 [15][16][17][18][19] ，我们在 2015 年成功开发了一个基于溶剂调控 的不对称合成的教学实验 [19b]…”

Metal-supported and -assisted stereoselective cooperative photoredox catalysis

“…The stereoselective construction of C-N bonds is a highly desirable reaction. [96][97][98][99][100][101][102] Conjugate amination of Michael systems is the general approach to access β-amino carbonyl compounds 71. [103][104][105][106] The reaction makes use of the inherently high nucleophilicity of the nitrogen atom, which in turn causes side reactions and hampers enantioselective addition.…”

“…[103][104][105][106] The reaction makes use of the inherently high nucleophilicity of the nitrogen atom, which in turn causes side reactions and hampers enantioselective addition. [96][97][98][99][100][101][102] Zhou et al used protoncoupled electron transfer (PCET) to convert N-H groups into nitrogen-centered radicals under mild conditions (Scheme 28). 107 The electron-deficient nature of such radicals, which makes direct addition to α,β-unsaturated compounds unfavorable, was bypassed by applying Δ-RhO as the Lewis acid catalyst in combination with an additional photocatalyst.…”

Stereoselective Synthesis of α-Amino-C-phosphinic Acids and Derivatives

“…Readily available enantiopure sulfinylimines also constitute valuable molecules in asymmetric synthesis [46]. Indeed, Petneházy et al [47] reported the synthesis of optically enriched α-amino-Cphosphinic acids using ethyl phenylphosphinate and chiral N-sulfinylaldimines.…”

“…For example, following the principle of activation of imines through hydrogen bonding, Tan et al [49] carried out the hydrophosphinylation reaction of the N-tosyl imines 18a-g with arylphosphinates and alkylphosphinates in the presence of catalytic amounts of the guanidinium salt 19·HBArF4 in a CH2Cl2:toluene mixture and K2CO3 as a base at −40 °C, obtaining the α-amino-C-phosphinates 20a-k in 71%-93% yield and 3:1-16:1 diastereoisomeric ratio, with preference for the diastereoisomers (RC,SP)-20a-k with 82%-94% enantiomeric excess (Scheme 13). Readily available enantiopure sulfinylimines also constitute valuable molecules in asymmetric synthesis [46]. Indeed, Petneházy et al [47] reported the synthesis of optically enriched α-amino-Cphosphinic acids using ethyl phenylphosphinate and chiral N-sulfinylaldimines.…”