Metal-Promoted Variants of the Passerini Reaction Leading to Functionalized Heterocycles

Xia, Qian; Ganem, Bruce

doi:10.1021/ol025877c

Cited by 82 publications

(30 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In a related approach, Xia and Ganem changed the carboxylic acid in the Passerini reaction to a Lewis acid (TMSOTf) to activate the carbonyl component. [27] The reaction of several aldehydes and ketones, morpholinoethyl isocyanide (20), and Zn(OTf) 2 /TMSCl (which forms TMSOTf in situ) resulted in the formation of a-hydroxyamides 23 (Scheme 3). A neighboring stabilizing group (such as the morpholine ring in this example) was shown to be required to stabilize the intermediate nitrilium ion 21, since the use of simple isocyanides did not afford products 23.…”

Section: Single Reactant Replacementmentioning

confidence: 99%

Multicomponent Reaction Design in the Quest for Molecular Complexity and Diversity

2011

View full text Add to dashboard Cite

Multicomponent reactions have become increasingly popular as tools for the rapid generation of small-molecule libraries. However, to ensure sufficient molecular diversity and complexity, there is a continuous need for novel reactions. Although serendipity has always played an important role in the discovery of novel (multicomponent) reactions, rational design strategies have become much more important over the past decade. In this Review, we present an overview of general strategies that allow the design of novel multicomponent reactions. The challenges and opportunities for the future will be discussed.

show abstract

Section: Single Reactant Replacementmentioning

confidence: 99%

Multicomponent Reaction Design in the Quest for Molecular Complexity and Diversity

2011

View full text Add to dashboard Cite

show abstract

“…The carbonyl group is one of the most critical reactants because of the pronouncedr eactivity of the isonitrile carbon atom towards the electrophilic sp 2 carbon center;t his reaction can be time consuming with low yields if it is not carriedo ut with as trong carboxylic acid or an unusually electrophilic carbonyl compound. [66] We carriedo ut the Passerini reactionb yu sing the one-pot methodology,a tr oom temperature, withouta ny solvent, and with 1mol %o fc atalyst. InPF-16, InPF-17,a nd InPF-18 materials demonstrated good catalytic activities ( Table 3, entries 1-3).…”

Section: Catalytic Activity Of Inpf Materialsmentioning

confidence: 99%

Synchronizing Substrate Activation Rates in Multicomponent Reactions with Metal–Organic Framework Catalysts

Aguirre-Díaz

Iglesias

Snejko

et al. 2016

Chemistry A European J

View full text Add to dashboard Cite

A study on the influence of the cation coordination number, number of Lewis acid centers, concurrent existence of Lewis base sites, and structure topology on the catalytic activity of six new indium MOFs, has been carried out for multicomponent reactions (MCRs). The new indium polymeric frameworks, namely [In8 (OH)6 (popha)6 (H2 O)4 ]⋅3 H2 O (InPF-16), [In(popha)(2,2'-bipy)]⋅3 H2 O (InPF-17), [In3 (OH)3 (popha)2 (4,4'-bipy)]⋅4 H2 O (InPF-18), [In2 (popha)2 (4,4'-bipy)2 ]⋅3 H2 O (InPF-19), [In(OH)(Hpopha)]⋅0.5 (1,7-phen) (InPF-20), and [In(popha)(1,10-phen)]⋅4 H2 O (InPF-21) (InPF=indium polymeric framework, H3 popha=5-(4-carboxy-2-nitrophenoxy)isophthalic acid, phen=phenanthroline, bipy=bipyridine), have been hydrothermally obtained by using both conventional heating (CH) and microwave (MW) procedures. These indium frameworks show efficient Lewis acid behavior for the solvent-free cyanosilylation of carbonyl compounds, the one pot Passerini 3-component (P-3CR) and the Ugi 4-component (U-4CR) reactions. In addition, InPF-17 was found to be a highly reactive, recyclable, and environmentally benign catalyst, which allows the efficient synthesis of α-aminoacyl amides. The relationship between the Lewis base/acid active site and the catalytic performance is explained by the 2D seven-coordinated indium framework of the catalyst InPF-17. This study is an attempt to highlight the main structural and synthetic factors that have to be taken into account when planning a new, effective MOF-based heterogeneous catalyst for multicomponent reactions.

show abstract

“…as 5 ) prior to hydrolytic workup. In support of that hypothesis, other isonitriles containing good donor groups, such as isocyanoacetate 6 or isocyanoacetamide 7 (Scheme 4) afforded the corresponding ethoxy or morpholinooxazoles 8 in good yield 10. Substituted oxazoles are active pharmacophores, and are also found in a variety of medicinally significant natural products.…”

Section: Early Examples Of the Srr Approachmentioning

confidence: 80%

Strategies for Innovation in Multicomponent Reaction Design

2009

Self Cite

View full text Add to dashboard Cite

CONSPECTUSBy generating structural complexity in a single step from three or more reactants, multicomponent reactions (MCRs) make it possible to synthesize target compounds with greater efficiency and atom economy. The history of such reactions can be traced to the mid-nineteenth century when Strecker first produced α-aminonitriles from the condensation of aldehydes with ammonia and hydrogen cyanide.Recently, academic chemists have renewed their interest in MCRs. In part, the pharmaceutical industry has fueled this resurgence because of the growing need to assemble libraries of structurally complex substances for evaluation as lead compounds in drug discovery and development programs. The application of MCRs to that increasingly important objective remains limited by the relatively small number of such reactions that can be broadly applied to prepare biologically relevant or naturalproduct-like molecular frameworks.We were interested in applying logic-based approaches, such as our single reactant replacement (SRR) approach, as a way both to improve known MCRs and design new multiple-component routes to bioactive structures. This Account provides several examples that illustrate the use of SRR with known MCRs as starting points for synthetic innovation in this area.As part of our working hypothesis, we initially explored strategies for engineering improvements into known MCRs, either by increasing the dimensionality-i.e. changing an n-component to an (n +1)-component reaction-or broadening the scope of useful input structures, or both. By exhaustively applying retrosynthetic analysis to the cognate MCR to identify and exploit alternative entry points into the overall reaction manifold, we have devised several such re-engineered MCRs. Serendipitous findings have also augmented the yield of useful developments from our logic-inspired approach. In some cases, we have identified surprising links between different compound families that provide useful new entry points for chemical library synthesis. In other cases, the same re-engineering logic made it possible (sometimes in unexpected ways) to transform certain non-elementary twocomponent reactions into higher order MCRs.While logic may also inspire the search for new MCRs, the design process requires added chemical creativity, which cannot be reduced to a simple formula. The long-term goal of our research is to expand the useful repertoire of such reactions, which are important as complexity-generating tools in both combinatorial and diversity-oriented synthesis. MCRs represent the cornerstones of both combinatorial chemistry and diversity-oriented synthesis, and thus have played a central role in the development of modern synthetic methodology for pharmaceutical and drug discovery research. 3 Used in conjunction with target-oriented synthesis, combinatorial chemistry approaches can be employed to introduce or broaden structural variations in a lead compound of interest. Diversity-oriented synthesis is helpful in exploring large areas of chemical structure space in ...

show abstract

Metal-Promoted Variants of the Passerini Reaction Leading to Functionalized Heterocycles

Cited by 82 publications

References 18 publications

Multicomponent Reaction Design in the Quest for Molecular Complexity and Diversity

Multicomponent Reaction Design in the Quest for Molecular Complexity and Diversity

Synchronizing Substrate Activation Rates in Multicomponent Reactions with Metal–Organic Framework Catalysts

Strategies for Innovation in Multicomponent Reaction Design

Contact Info

Product

Resources

About