A variety of inert tertiary amides have been successfully transformed into synthetically important chiral propargylamines in high yields with good to excellent enantioselectivities via a relayed ...sequence of Ir catalyzed partial reduction and Cu/GARPHOS catalyzed asymmetric alkynylation with terminal alkynes. The reaction was readily extended to some drug molecules and the transformations of representative products have been demonstrated, thus attesting the practical utilities and the robust nature of the protocol.
An Ir/Cu bimetallic relay catalysis was developed to achieve the challenging asymmetric deoxygenative alkynylation of inert amides under mild conditions, affording a series of synthetically important chiral propargylamines in high yields with good to excellent enantioselectivities.
Reported herein is the first direct, metal‐catalyzed reductive functionalization of secondary amides to give functionalized amines and heterocycles. The method is shown to have exceptionally broad ...scope with respect to suitable nucleophiles, which cover both hard and soft C nucleophiles as well as a P nucleophile. The reaction exhibits good chemoselectivity and tolerates several sensitive functional groups.
A soft touch: A versatile, direct, metal‐catalyzed reductive functionalization reaction of secondary amides, to give functionalized amines and heterocycles, was developed. A broad substrate scope for both the amide and nucleophile was observed. Viable nucleophiles include reactive and soft C nucleophiles as well as a P nucleophile. The reaction exhibits good chemoselectivity and tolerates several sensitive functional groups (FGs).
We report herein a convenient and versatile method for the direct reductive alkynylation of tertiary amides to give propargylic amines through sequential Ir-catalysed hydrosilylation-Cu(i)-catalysed ...alkynylation. The reactions proceed chemoselectively at the amide group in the presence of several sensitive functional groups including the very reactive aldehyde group on either the amide or the alkyne coupling partner. The method is general for tert-amides with or without α-hydrogen.
Abstract
The powerful insecticidal and multi-drug-resistance-reversing activities displayed by the stemofoline group of alkaloids render them promising lead structures for further development as ...commercial agents in agriculture and medicine. However, concise, enantioselective total syntheses of stemofoline alkaloids remain a formidable challenge due to their structural complexity. We disclose herein the enantioselective total syntheses of four stemofoline alkaloids, including (+)-stemofoline, (+)-isostemofoline, (+)-stemoburkilline, and (+)-(11
S
,12
R
)-dihydrostemofoline, in just 19 steps. Our strategy relies on a biogenetic hypothesis, which postulates that stemoburkilline and dihydrostemofolines are biogenetic precursors of stemofoline and isostemofoline. Other highlights of our approach are the use of Horner–Wadsworth–Emmons reaction to connect the two segments of the molecule, an improved protocol allowing gram-scale access to the tetracyclic cage-type core, and a Cu-catalyzed direct and versatile nucleophilic alkylation reaction on an anti-Bredt iminium ion. The synthetic techniques that we developed could also be extended to the preparation of other
Stemona
alkaloids.
The catalytic conversion of amides to ketones is highly desirable yet challenging in organic synthesis. We herein report the first Ni/bis-NHC-catalyzed cross-coupling of N-acylpyrrole-type amides ...with arylboronic esters to obtain diarylketones. This method is facilitated by a new chelating bis-NHC ligand. The reaction tolerates diverse functional groups on both arylamide and arylboronic ester partners including sensitive ester and ketone groups.
Although the asymmetric catalysis has made a spurt of progress, the use of chiral auxiliaries remains crucial in asymmetric synthesis due to both the reliability and versatility of the methods, and ...the predictability of stereochemistry of the reactions. Up to date, Evans’ chiral non‐racemic oxazolidinone‐based asymmetric synthetic methodology is still widely used in asymmetric synthesis. More importantly, the Evans asymmetric synthetic methodology turned out to be a fruitful source of inspiration for the development of related asymmetric synthetic methodologies. However, although reviews on the application of Evans’ asymmetric synthetic methodology in both organic synthesis and medicinal chemistry continually to appear in the literature, a comprehensive review dedicating to the extensions of Evans’ chiral non‐racemic oxazolidinone‐based asymmetric methodology remains elusive. In this review, we summarize the extensions of the Evans asymmetric methodology, which cover: (1) the modification of the chiral oxazolidinone auxiliaries; (2) the extension of the Evans’ asymmetric aldol reaction from Evans’ syn‐aldol to other diastereomeric aldol adducts; (3) the extension of the asymmetric reaction types; (4) the extension of chiral imide‐type substrates to N‐alkenyl, N‐allenenyl and N‐alkynyl oxazolidinones; (5) the achiral oxazolidinone‐based asymmetric catalysis; (6) the catalytic transformation of Evans’ products; and (7) the straightforward transformations of Evans’ chiral products to other classes of compounds than the chiral carboxylic acids, esters, alcohols, and Weinreb amides.
In this review, the extensions of the Evans asymmetric methodology are summarized from seven aspects. It also indicates that the asymmetric methodology still stands as an indispensable tool for accessing enantiomeric natural products and medicinal agents due to the reliability, scalability, and predictability.
The combination of transition‐metal catalysis and organocatalysis increasingly offers chemists opportunities to realize diverse unprecedented chemical transformations. By combining iridium with ...chiral thiourea catalysis, direct enantioselective reductive cyanation and phosphonylation of secondary amides have been accomplished for the first time for the synthesis of enantioenriched chiral α‐aminonitriles and α‐aminophosphonates. The protocol is highly efficient and enantioselective, providing a novel route to the synthesis of optically active α‐functionalized amines from the simple, readily available feedstocks. In addition, the reactions are scalable and the thiourea catalyst can be recycled and reused.
The first enantioselective reductive cyanation and phosphonylation of secondary amides have been achieved by the combination of iridium with chiral thiourea catalysis. The protocol is highly efficient and enantioselective, providing a novel route for the synthesis of optically active α‐aminonitriles and α‐aminophosphonates from bench‐stable feedstocks.
Versatile and mild: The first general method for the title transformation has been developed (see scheme; 2‐F‐Py=2‐fluoropyridine; Tf=trifluorosulfonyl). The amines are synthesized in good yields and ...the ketimine intermediates can be isolated before the reduction. This method should find applications in the synthesis of nitrogen‐containing bioactive molecules and medicinal agents.
Although N -acyloxazolidinone-based (catalytic) asymmetric synthetic methodologies occupy an important position in modern organic synthesis, the catalytic cleavage of a chiral auxiliary remains ...underdeveloped. We report the Ni(cod) 2 /bipyr.-catalyzed alcoholysis of N -acyloxazolidinones to deliver esters. The reaction is broad in scope for both N -acyloxazolidinone substrates and alcohol nucleophiles, and displays good functional group tolerance and excellent chemoselectivity. A gram-scale methanolysis allowed the enantioselective synthesis of the C22–C26 segment of a close analogue of the potent immunosuppressant agent FK506.
The efficiency becomes a key issue in today's natural product total synthesis. While biomimetic synthesis is one of the most elegant strategies to achieve synthetic efficiency and thus to approach ...the ideal synthesis, most biogenetic pathways are unknown or unconfirmed. In this account, we demonstrate, through the shortest and also the most efficient asymmetric total syntheses of the hexacyclic alkaloid (−)‐chaetominine to date, that on the basis of biogenetic thinking, one can develop quite efficient bio‐inspired total synthesis, which in turn serves to suggest and chemically validate plausible biosynthetic routes for the natural product. The synthetic strategy thus developed is also inspiring for the development of other synthetic methods and efficient total synthesis of other natural products.
With biogenetic thinking, the hexacy‐clic alkaloid (−)‐chaetominine has been synthesized in only four steps from d‐tryptophan and in just five steps from L‐tryptophan. This short‐step generation of molecular complexity by chemical synthesis established several records in terms of steps, overall yields, and starting point.
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