高烯丙醇和高烯丙胺的电化学合成研究进展

电化学技术已经在有机合成得到广泛重视,本文简要概述了利用羰基和亚胺的电化学烯丙基化反应合成高烯丙醇和高烯丙胺的方法. 该方法已经得到了比较瞩目的进展,特别是在水相中的电化学烯丙基化反应,充分体现了绿色化学的特点。在提高电流效率和区域选择性,利用手性催化剂进行手性合成等方面还期待更多的关注和发展.     

Diastereoselective Cyanation of α‐Keto Amides Derived from N‐Phenyl Camphorpyrazolidinone and Camphorsultam

The diastereoselective cyanation of α‐keto amides using trimethylsilyl cyanide in the presence of a Lewis acid is described. The corresponding O‐acetylated cyanohydrins are obtained in good to high levels of stereoselectivities. The predominance of products with the S absolute configuration at the newly generated stereogenic center was deduced from single crystal X‐ray analysis. ¹³C NMR data suggest that a preferential s‐cis conformation was formed by the chelation of a Lewis acid to the dicarbonyl oxygen atoms.     

Sequential Ir‐Catalyzed Allylation/2‐aza‐Cope Rearrangement Strategy for the Construction of Chiral Homoallylic Amines†

Sequential Ir‐catalyzed asymmetric allylation/2‐aza‐Cope rearrangement of arylidene aminomalonates with allylic carbonates was successfully developed, and a variety of enantioenriched homoallylic amine derivatives were obtained in high yields with good chirality transfer and excellent E/Z‐geometry control (up to 99% yield, 96% ee). Compared with previous dual catalytic system established for this transformation, the current mono metal catalytic system provides a simpler and more practical protocol employing the readily available starting materials.     

Diastereoselective Epoxidation of Camphor N‐Enoylpyrazolidinones

Reaction of camphor N‐enoylpyrazolidinones ( 1a‐j ) with various oxidants, in particular UHP/TFAA afford chiral epoxides with a wide range of stereoselectivities (up to > 90% de).     

Diastereoselective allylation of α-ketoamides bearing camphor N-tosylpyrazolidinone auxiliary: efficient synthesis of highly optically active two stereoisomers

Complementary allylation conditions were developed for the synthesis of both diastereomers of tertiary homoallylic alcohols. Treatment of camphor N-tosylpyrazolidinone derived α-ketoamides with allyltributylstannane afforded both the individual homoallylic alcohols in high optical purity (up to 98% de) when the reaction was carried out in the presence of Sn(OTf)₂ and PdCl₂, respectively. The stereochemical outcome and reversal of stereoselectivity in the reaction are proposed based on ¹³C NMR and FTIR studies.     

水相中磷钼酸催化三组分合成烯丙基胺

以磷钼酸作为催化剂，芳香醛、胺和三丁基烯丙基锡三组分在水作为溶剂，室温下高产率的得到相应的烯丙基胺。     

A Facile and Efficient Synthesis of Substituted Pyrroles by Three Component Coupling Reaction of Amines, Aldehydes and Nitroalkanes

A facile and efficient synthesis of highly substituted pyrroles has been achieved by a one-pot three-component coupling reaction of aldehyde, amine and nitroalkane by triethyl orthoformate.     

Facile Synthesis of N‐Carboranyl Amines through an ortho‐Carboryne Intermediate

The efficient o‐carboryne precursor 1‐Li‐2‐OTf‐o‐C₂B₁₀H₁₀ reacts with lithium amides at room temperature to give a series of N‐carboranyl amines in moderate to high isolated yields. This reaction is compatible with a broad substrate scope from primary to secondary, alkyl to aryl amines. The reaction mechanism is also proposed on the basis of experimental results and DFT calculations. This represents the first general and efficient method for the synthesis of 1‐NR¹R²‐o‐carboranes.     

Asymmetric Synthesis of β2‐homo‐tert‐Leucine via Radical Addition to Enantiopure N‐Fumaroylhexahydrobenzooxazolidin‐2‐one

β‐Amino acids are key structural elements in unnatural peptides, peptidomimetics, and many other physiologically active compounds. In view of their importance, we have developed an efficient synthetic route that provides highly enantiomerically enriched (R)‐ and (S)‐H‐β²‐h^tLeu‐OH via highly diastereo‐ and regioselective addition of tert‐butyl radical to enantiomerically pure N‐fumaroyloxazolidinones, followed by removal of the chiral auxiliary, Curtius rearrangement, ester hydrolysis, and catalytic hydrogenolysis.     

Zirconyl Chloride (= Dichlorooxozirconium) as an Efficient Catalyst for One‐Pot Multicomponent Synthesis of Homoallylic Amines

Zirconyl chloride (ZrOCl₂) catalyzes efficiently the one‐pot three component reactions of aldehydes, amines, and allyltributylstannane at room temperature to furnish the corresponding homoallylic amines in short reaction times and in excellent yields.     

手性高烯丙基胺的合成及表征——一个微量不对称合成教学实验

描述了一个以立体化学中非对映选择性为知识重点,以无水无氧操作为操作重点的微量不对称合成实验。(R)-N-叔丁基亚磺酰亚胺在无水无氧环境中,经过锌参与的烯丙基化,在不同的溶剂、添加剂条件下以不同的选择性得到了一对非对映异构体,以较高的产率得到终产物。烷基化反应产物的非对映体比率(dr)通过1H与19FNMR以及手性HPLC确定。总体来说,这一实验所用试剂易得,反应条件温和,速率快,产率高;学生在学习无水无氧操作(Schlenk技术)的同时,还能够熟悉立体化学的基本概念,了解如何通过调节反应溶剂和添加剂实现立体化学结果的逆转,并掌握使用手性HPLC和NMR确定光学活性物质的dr值的方法。     

Transition‐Metal‐Free Hydrogen Autotransfer: Diastereoselective N‐Alkylation of Amines with Racemic Alcohols

A practical method for the synthesis of α‐chiral amines by alkylation of amines with alcohols in the absence of any transition‐metal catalysts has been developed. Under the co‐catalysis of a ketone and NaOH, racemic secondary alcohols reacted with Ellman's chiral tert‐butanesulfinamide by a hydrogen autotransfer process to afford chiral amines with high diastereoselectivities (up to >99:1). Broad substrate scope and up to a 10 gram scale production of chiral amines were demonstrated. The method was applied to the synthesis of chiral deuterium‐labelled amines with high deuterium incorporation and optical purity, including examples of chiral deuterated drugs. The configuration of amine products is found to be determined solely by the configuration of the chiral tert‐butanesulfinamide regardless of that of alcohols, and this is corroborated by DFT calculations. Further mechanistic studies showed that the reaction is initiated by the ketone catalyst and involves a transition state similar to that proposed for the Meerwein–Ponndorf–Verley (MPV) reduction, and importantly, it is the interaction of the sodium cation of the base with both the nitrogen and oxygen atoms of the sulfinamide moiety that makes feasible, and determines the diastereoselectivity of, the reaction.     

金属参与的N-酰基腙的偕二氟烯丙基化反应：高效合成偕二氟高烯丙基胺

金属铟参与醛衍生的N-酰基腙 1a-1q,4a-4g与3-溴-3,3-二氟丙烯 2 的反应,分别高效得到α, α-二氟高烯丙基肼 3a-3q,5a-5g。该反应条件温和,操作简便。硝基,酚羟基,苄氧基,α, β-不饱和醛的碳-碳双键等官能团对该反应具有良好的官能团兼容性。通过用锌粉代替铟粉, 酮衍生的N-酰基腙 6a-6d 也能发生偕二氟烯丙基化反应,以中等产率得到α, α-二氟高烯丙基肼 7a-7d。裂解肼3a的 N-N键顺利得到偕二氟高烯丙基胺 8,化合物 8 经丙烯酰化,随后进行RCM关环反应,可以方便的转化为偕二氟-γ-取代α, β-不饱和内酰胺 11。     

Asymmetric Catalytic Aminoalkylations: New Powerful Methods for the Enantioselective Synthesis of Amino Acid Derivatives,Mannich Bases,and Homoallylic Amines

Modern methodologies such as the design of chiral catalysts using combinatorial techniques play a key role in the development of asymmetric aminoalkylations. Thus, powerful enantioselective syntheses for many attractive target compounds using chiral Lewis acid or base catalysts like 1 or 2 were created.     

Highly cis‐Diastereoselective Synthesis of Coumarin‐Based 2,3‐Disubstituted Dihydrobenzothiazines by Organocatalysis

An efficient and organocatalyzed asymmetric reaction of phenacyl halides with coumarin‐based dihydrobenzothiazoles was developed to afford cis‐2,3‐disubstituted 3,4‐dihydro‐2H‐benzothiazines. This method provides a one‐step and highly diastereoselective route to a wide variety of coumarin‐based 3,4‐dihydro‐2H‐benzothiazines using the cheap and commercially available Cinchona alkaloid quinine hydrochloride.     

On the scope of diastereoselective allylation of various chiral glyoxylic oxime ethers with allyltributylstannane in the presence of a Lewis acid and triallylaluminum

The nucleophilic allylation of various chiral auxiliaries derived glyoxylic oxime ethers was studied. The use of allyltributylstannane in the presence of a Lewis acid and triallylaluminum provided the corresponding homoallylic amines in high chemical yields (up to 89%) and excellent stereoselectivities (up to >99%). The stereochemical bias of the allylation is proposed.