The Growing Synthetic Utility of Weinreb′s Amide
01 Apr 2000-Journal Fur Praktische Chemie-chemiker-zeitung (WILEY‐VCH Verlag GmbH)-Vol. 342, Iss: 4, pp 340-347
TL;DR: In this article, the preparation and the synthetic utility of Weinreb amides for the preparation of aldehydes and ketones has been discussed, and various reagents based on Weinreb′s amide have been compiled.
Abstract: The preparation and the synthetic utility of the N-methoxy-N-methyl amides, also called as Weinreb amides, for the preparation of aldehydes and ketones has been discussed. Also the various reagents based on Weinreb′s amide has been compiled.
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TL;DR: The purpose of this Review is to serve as a teaching tool for all practitioners of the field by giving and illustrating guidelines to increase redox economy in multistep organic synthesis.
Abstract: "Economy" is referred to as the thrifty and efficient use of material resources, as the principle of "minimum effort to reach a goal." More illuminating is: "the aim to portion one's forces in order to use as little as possible of them to reach a goal." Such statements certainly apply when the goal is to synthesize a complex target molecule. Redox economy then implies the use of as few redox steps as possible in the synthetic conquest of a target compound. While any sort of economy will help to streamline the effort of total synthesis, redox economy addresses a particularly weak area in present-day total synthesis. It is not enough to point out the present deficiencies, rather the purpose of this Review is to serve as a teaching tool for all practitioners of the field by giving and illustrating guidelines to increase redox economy in multistep organic synthesis.
611 citations
TL;DR: In this Minireview examples of newer stoichiometric and catalytic methods are summarized which have proved their suitability for the enantioselective construction of quaternary stereocenters.
Abstract: The stereoselective formation of C-C bonds is of great importance for the synthesis of enantiomerically pure natural products and pharmaceuticals. A broad repertoire of chiral auxiliaries, reagents, and catalysts can be utilized for the reliable generation of tertiary stereocenters. In contrast, the synthesis of organic compounds with quaternary stereocenters is a much more demanding and challenging task. Every enantioselective synthetic method can demonstrate its value through the generation of a fully substituted carbon center. In this Minireview examples of newer stoichiometric and catalytic methods are summarized which have proved their suitability for the enantioselective construction of quaternary stereocenters.
561 citations
263 citations
TL;DR: Mild decarboxylative arylation of α-oxo acids has been achieved by synergistic visible-light-mediated photoredox and nickel catalysis and can be utilized to efficiently access medicinal agents, as demonstrated by the rapid synthesis of fenofibrate.
Abstract: The direct decarboxylative arylation of α-oxo acids has been achieved by synergistic visible-light-mediated photoredox and nickel catalysis. This method offers rapid entry to aryl and alkyl ketone architectures from simple α-oxo acid precursors via an acyl radical intermediate. Significant substrate scope is observed with respect to both the oxo acid and arene coupling partners. This mild decarboxylative arylation can also be utilized to efficiently access medicinal agents, as demonstrated by the rapid synthesis of fenofibrate.
239 citations
TL;DR: The nucleophilic addition of carbon nucleophiles to amides has traditionally been a difficult task, both due to reactivity and selectivity problems as mentioned in this paper, and only scattered applications on particular substrates have appeared.
Abstract: The nucleophilic addition of carbon nucleophiles to amides has traditionally been a difficult task, both due to reactivity and selectivity problems. When successful, these processes would represent straightforward routes towards carbonyl-type or amine compounds, depending on the fate of the generated tetrahedral intermediate. The direct addition of nucleophiles to amides for the preparation of ketones has been studied and applied to the syntheses of several natural products. On the other hand, the addition of nucleophiles to amides to obtain substituted amines represented a major challenge, and only scattered applications on particular substrates have appeared. Initial improvements were based on the activation of amides by introduction of particular substituents, such as in N-methoxy amides (Weinreb amides) or electron-withdrawing groups able to increase the carbon nucleophilicity. Although these strategies facilitate the introduction of nucleophiles, chemoselectivity issues arise when additional electrophilic moieties (i.e., carbonyls) are present, thus decreasing the versatility of the methods. In recent years, important advancements towards fully chemoselective methods have been realized. The capture of tetrahedral intermediates with acids generates highly electrophilic iminium species able to undergo chemoselective additions of various nucleophiles, thus accessing substituted amines. Alternatively, the in situ generation of an iminium triflate ion allows highly chemoselective additions of nucleophiles, yielding amines, ketones or ketimines. Also thioamides can be used as precursors of ketones or alpha-substituted amines. The success of the above methodologies is further showcased by the application in various syntheses of natural products or biologically active molecules.
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References
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TL;DR: Readily preparable N-methoxy-N-methylamides couple in good yields with Grignard and organolithium reagents to produce ketones, and are reduced with hydrides to afford aldehydes.
1,611 citations
TL;DR: In this paper, two key improvements in the osmiuun-catalyzed asymmetric dihydroxylation have led to a simple procedure which is applicable to a wide range of olefins.
Abstract: Two key improvements in the osmiuun-catalyzed asymmetric dihydroxylation have led to a simple procedure which is applicable to a wide range of olefins.
1,327 citations
TL;DR: The first synthesis of the macrolide insecticide A83543A (lepicidin A) has been completed using a Diels-Alder strategy to construct the carbocyclic framework.
Abstract: The first synthesis of the macrolide insecticide A83543A (lepicidin A) has been completed using a Diels-Alder strategy to construct the carbocyclic framework. Diene synthesis through Pd-catalyzed Stille coupling of a macrocyclic vinylstannane and suitably functionalized vinyl iodide was followed by a diastereoselective Lewis acid-mediated intramolecular Diels-Alder reaction to construct the trans hydrindene subunit. Refunctionalization and intramolecular aldol condensation afforded the differentially protected (+)-lepicidin A aglycon. Successive glycosidations with 2,3,4-tri-O-methyl-D-rhamnose and N-protected L-forosamine followed by deprotection and methylation completed the synthesis of the enantiomer of the natural product
267 citations
TL;DR: A convergent asymmetric synthesis of the antinoeplastic macrolide antibiotic cytovaricin has been achieved through the synthesis and coupling of the illustrated spiroketal and polyol glycoside subunits.
Abstract: A convergent asymmetric synthesis of the antinoeplastic macrolide antibiotic cytovaricin has been achieved through the synthesis and coupling of the illustrated spiroketal and polyol glycoside subunits. All absolute steroechemical relationships within the target structure were ultimately controlled by the use of asymmetric aldol, alkylation, or epoxidation methodology. Union of the two subnits was accomplished by Julia-Lythgoe trans olefination, providing direct access to a suitable macrolactonization substrate
261 citations
TL;DR: In this article, a convergent asymmetric synthesis of the polyether antibiotic X-206 has been achieved through the synthesis and coupling of the CI-C16 and C17-C37 synthons 16 and 17, respectively.
Abstract: A convergent asymmetric synthesis of the polyether antibiotic X-206 has been achieved through the synthesis and coupling of the CI-C16 and C17-C37 synthons 16 and 17, respectively. All absolute stereochemical relationships within the molecule were controlled by application of recent methodological advances in asymmetric synthesis. In the synthesis of subunit 16, both the alkylation and aldol reactions of chiral imide-derived enolates were utilized to establish the five stereogenic centers at C2-C4 and C9-CIo, while the stereochemistry at C14 was indirectly controlled by the Sharpless asymmetric epoxidation. The C7 and Cl l stereocenters, which are situated at the two assemblage pints for 16, were established through internal asymmetric induction. The synthesis of the more complex c17<37 subunit 17 followed a similar strategy for absolute stereocontrol. Chiral enolate methodology was employed to define the stereogenic centers at C18, C,,, and C23 while asymmetric epoxidation was used to create the oxygen-bearing centers at C30-C31 and Cj4-C3). The remaining three stereogenic centers at Cz0, C,,, and C28 were controlled by internal asymmetric induction. The successful construction of this synthon relied upon the development of an efficient assemblage reaction in which three fragments comprising the entire carbon framework of 17 were united in
216 citations