亚砜类化合物的合成及应用进展

亚砜类化合物作为一种重要的中间体备受关注,学者们一直努力寻找合适的合成方法.综述了亚砜类化合物的合成方法及应用方面的研究进展,并对发展趋势和应用前景做了展望.     

亚砜化合物的生物活性研究和不对称合成进展

亚砜类化合物在有机合成和药物化学中有着广泛的应用,手性亚砜作为助剂、配体、催化剂和合成子的用途已得到充分证明,亚砜类化合物的亚磺酰基团也可作为药效团、羰基生物等排体或药物分子修饰基团应用于药物设计和药物开发之中.综述了具有生物活性的亚砜类化合物的结构骨架以及相应的作用机制,并总结了近十年来通过构建硫立体中心制备手性亚砜类化合物的新方法和新进展,具体到廉价金属铁络合物、多金属氧酸盐、有机小分子、生物酶和电化学催化的硫醚不对称氧化反应,以及基于次磺酸阴离子中间体的手性亚砜合成策略和最近涌现的新策略,其中也包括作者最近在手性亚砜合成领域取得一些研究成果.     

通过不对称多组分反应高效构建手性磺酰胺类化合物

手性磺酰胺类化合物在新型药物方面研究中占据越来越重要的地位.我们成功地实现了磺酰胺、芳基重氮乙酸酯以及亚胺的不对称三组分反应.此反应给出了高达85%产率,以及优异的非对映选择性（d.r.>20：1）和对映选择性（最高可达99%ee）,为高效构建具有两个手性碳的光学纯磺酰胺类化合物提供了一种快速合成方法.我们将反应放大到了克级规模,并对三组分产物进一步衍生得到一种具有三个手性中心的光学纯含亚砜亚胺骨架的五元环化合物.反应的选择性通过过渡金属与手性磷酸协同催化控制.     

1,8-萘二酰亚胺与炔类的光化环加成反应

酰亚胺类化合物与烯烃的光化反应是有机光化学中的一个重要而活跃的领域.这些反应不仅对光化学的机理研究做出了很大贡献,而且在合成杂环以及中到大环化合物方面具有很高的合成价值.为了扩大这一领域的研究范围,我们把反应物从烯烃扩大至炔烃.本文报道1,8-萘二酰亚胺与炔类化合物的光化反应.     

吲哚马来酰亚胺类蛋白激酶C抑制剂的研究进展

吲哚马来酰亚胺类化合物是对星型孢菌素进行结构改造而得到的一类新型蛋白激酶C抑制剂. 对近年来吲哚马来酰亚胺类化合物在结构修饰、合成和生物活性等方面的研究进行了总结和概述, 重点介绍了吲哚马来酰亚胺类化合物的合成方法, 讨论了各种合成方法的优缺点.     

N-氟代双苯磺酰胺作为氧化剂制备二硫化合物的研究（英文）

建立了一种以N-氟代双苯磺酰胺(NFSI)为氧化剂合成二硫化合物的新方法.该方法反应温和、操作简便、反应时间短并无过度氧化的副产物(亚砜或砜类化合物)生成.     

α-乙酰基二硫缩烯酮Vilsmeier反应在共轭三烯化合物合成中的应用

以α-乙酰基二硫缩烯酮为起始原料,通过与Vilsmeier试剂反应得到亚胺盐正离子中间体,利用亚胺盐正离子中间体与碳亲核体反应,成功制备了多取代共轭三烯类化合物.该方法具有原料易得、反应条件温和及实验步骤简单等优点.该反应不仅建立了一种简单、有效合成多取代共轭三烯化合物新方法,而且扩展了α-乙酰基二硫缩烯酮类化合物在有机合成中的进一步应用.     

高烯丙基酰肼氧化/卤胺环化串联反应合成吡唑啉类化合物（英文）

探索了以N-碘代丁二酰亚胺(NIS)作为卤化试剂,通过高烯丙基酰肼化合物的串联氧化/卤胺环化反应合成吡唑啉类化合物.该方法反应条件温和,不需要添加剂,以良好的收率得到吡唑啉类化合物.     

芳杂环亚胺类化合物的研究进展

芳杂环亚胺类化合物因其特有的C=N键,具有很强的生物活性,在医药、材料、农业和染料等领域应用十分广泛。芳杂环亚胺类化合物也是一类重要有机中间体,可以发生还原、加成、环氧化等众多有机反应,更是杂环合成中的重要前体之一。本文围绕着芳杂环亚胺类化合物的种类、应用和国内外研究进展进行综述,为日后合成芳杂环亚胺类化合物提供一定参考。     

N-苄基亚砜亚胺的绿色合成及其抑菌活性

以易制备的无保护NH-亚砜亚胺和廉价易得的取代甲苯为原料,利用可见光催化策略,在较为温和的条件下实现了NH-亚砜亚胺和取代甲苯的偶联反应。考察了不同光催化剂、碱和溶剂等因素对反应的影响,筛选出了最优的反应条件,拓展了亚砜亚胺和甲苯的底物范围,并对产物的抑菌活性进行了初步研究。结果表明,反应最佳条件为：亚砜亚胺（0.2 mmol）,甲苯（0.24 mmol）,碳酸钾（0.26 mmol）,曙红Y(0.02 mmol),NBS (0.26 mmol),异丙醇（1 mL）,在18 W蓝光LED光照下,室温反应24 h。该反应体系对不同的亚砜亚胺底物和甲苯底物均有良好的适用性,产率在46%～75%。在16个被试化合物中,有7个化合物对大肠杆菌有抑制作用,6个化合物对金黄色葡萄球菌有抑制作用。     

Synthesis and Transformations of NH-Sulfoximines

Recent years have seen a marked increase in the occurrence of sulfoximines in the chemical sciences, often presented as valuable motifs for medicinal chemistry. This has been prompted by both pioneering works taking sulfoximine containing compounds into clinical trials and the concurrent development of powerful synthetic methods. This review covers recent developments in the synthesis of sulfoximines concentrating on developments since 2015. This includes extensive developments in both S−N and S−C bond formations. Flow chemistry processes for sulfoximine synthesis are also covered. Finally, subsequent transformations of sulfoximines, particularly in N-functionalization are reviewed, including N−S, N−P, N−C bond forming processes and cyclization reactions.     

Asymmetric Synthesis of Chiral Sulfoximines through the S‐Alkylation of Sulfinamides

Innovation in drug discovery critically depends on the development of new bioisosteric groups. Chiral sulfoximines, which contain a tetrasubstituted sulfur atom that bears one nitrogen, one oxygen, and two different carbon substituents, represent an emerging chiral bioisostere in medicinal chemistry. Chiral sulfoximines are conventionally prepared by a stereospecific nitrene transfer reaction to chiral sulfoxides; however, the number of readily available chiral sulfoxides remains limited. Herein, we report the asymmetric synthesis of a class of hitherto difficult‐to‐access chiral sulfoximines with two structurally similar alkyl chains. Our synthetic approach is based on the sulfur‐selective alkylation of easily accessible chiral sulfinamides with commercially available reagents under simple and safe conditions. This stereospecific S‐alkylation offers a general and scalable approach to the asymmetric synthesis of chiral sulfoximines, which represent important substructures in bioactive molecules.     

Synthesis of N-(1H)-tetrazole sulfoximines

N-(1H)-Tetrazole sulfoximines are readily available by addition of sodium azide to the corresponding N-cyano derivatives in the presence of ZnBr2. The use of these N-(1H)-tetrazoles as intermediates in the synthesis of other N-heterocyclic sulfoximines is demonstrated.     

Sigmatropic Rearrangement of Vinyl Aziridines: Expedient Synthesis of Cyclic Sulfoximines from Chiral Sulfinimines

A novel rearrangement of 2‐vinyl aziridine 2‐carboxylates to unusual chiral cyclic sulfoximines is described herein. The method allows the synthesis of substituted cyclic sulfoximines in high yields with complete stereocontrol, and tolerates a wide substrate scope. A one‐pot process starting directly from sulfinimines provides access to complex chiral sulfoximines in only two steps from commercially available aldehydes. A mechanistic hypothesis and synthetic application in the formal synthesis of trachelanthamidine, by transformation of a cyclic sulfoximine into a pyrroline, is also disclosed.     

Palladium catalyzed aroylation of NH-sulfoximines with aryl halides using chloroform as the CO precursor

A palladium-catalyzed aroylation of NH-sulfoximines for the efficient synthesis of N-aroyl sulfoximines from aryl halides and chloroform has been developed. The mild reaction conditions (temperature, catalyst loading) and the use of a CO surrogate render this transformation a useful method for the synthesis of N-aroyl sulfoximines from available feedstock.     

Efficient Synthesis of Cyclic Sulfoximines from N-Propargylsulfinamides through Sulfur–Carbon Bond Formation

Cyclic sulfoximines were readily synthesized by the cyclization of N-propargylsulfinamides without using expensive and toxic metal catalysts. This cyclization proceeded without loss of optical purity of chiral sulfinamides through the unusual sulfur–carbon bond formation promoted by an inexpensive inorganic base. This stereospecific cyclization offers a general approach to the asymmetric synthesis of chiral cyclic sulfoximines as an emerging heterocycle in medicinal chemistry.     

Synthesis of Chiral Sulfoximines via Iridium-Catalyzed Regio- and Enantioselective C−H Borylation: A Remarkable Sidearm Effect of Ligand

Transition metal-catalyzed enantioselective C−H activation of prochiral sulfoximines for non-annulated products remains a formidable challenge. We herein report iridium-catalyzed enantioselective C−H borylation of N-silyl diaryl sulfoximines using a well-designed chiral bidentate boryl ligand with a bulky side arm. This method is capable of accommodating a broad range of substrates under mild reaction conditions, affording a vast array of chiral sulfoximines with high enantioselectivities. We also demonstrated the synthetic utility on a preparative-scale C−H borylation for diverse downstream transformations, including the synthesis of chiral version of bioactive molecules. Computational studies showed that the bulky side arm of the ligand confers high regio- and enantioselectivity through steric effect.     

Efficient Kinetic Resolution of Sulfur‐Stereogenic Sulfoximines by Exploiting CpXRhIII‐Catalyzed C−H Functionalization

Chiral sulfoximines with stereogenic sulfur atoms are promising motifs in drug discovery. We report an efficient method to access chiral sulfoximines through a C?H functionalization based kinetic resolution. A rhodium(III) complex equipped with a chiral Cp^x ligand selectively participates in conjunction with phthaloyl phenylalanine in the C?H activation of just one of the two sulfoximine enantiomers. The intermediate reacts with various diazo compounds, providing access to chiral 1,2‐benzothiazines with synthetically valuable substitution patterns. Both sulfoximines and 1,2‐benzothiazines were obtained in high yields and excellent enantioselectivity, with s‐values of up to 200. The utility of the method is illustrated by the synthesis of the key intermediates of two pharmacologically relevant kinase inhibitors.     

Synthesis of Sulfoximidoyl‐Containing Hypervalent Iodine(III) Reagents and Their Use in Transition‐Metal‐Free Sulfoximidations of Alkynes

Well‐defined hypervalent iodine(III) reagents incorporating transferable sulfoximidoyl groups were obtained through ligand exchange reactions of methoxy(tosyloxy)iodobenzene (MTIB) with NH sulfoximines in good to excellent yields. The solid‐state structure of a representative product was characterized by X‐ray crystallography. Utilizing these reagents in synthesis provides a new, transition‐metal‐free approach towards N‐alkynylated sulfoximines.     

Asymmetric synthesis of highly substituted azapolycyclic compounds via 2-alkenyl sulfoximines: potential scaffolds for peptide mimetics

The application of metalated, enantiomerically pure acyclic and cyclic 2-alkenyl sulfoximines for the synthesis of highly substituted aza(poly)cyclic ring systems is described. The method relies on a one-pot combination of a reagent-controlled allyl transfer reaction to alpha- or beta-amino aldehydes, followed by a Michael-type cyclization of the intermediate vinyl sulfoximines generated in the first step. The sulfur-free target compounds are preferentially obtained by samarium iodide treatment of the sulfonimidoyl substituted heterocycles. In addition to this methodological work, initial results on the biological activity of selected examples are reported. Furthermore, a concept for the transformation of peptidic lead structures into non-peptide mimetics is described, and the relevance of the new approach to highly substituted azaheterocycles in this context is discussed.