Aldehydes natural product/pharmaceutical

Oxa-tetrahydropyridines are interesting intermediates for the preparation of pharmaceuticals and natural product based alkaloid systems. A modified Hantzsch reaction was developed under microwave irradiation for the preparation of 2-oxa-tetrahydropyridines 173 by reaction of Meldrum s acid, a /3-ketoester and an aldehyde, using NH4OAC as the source of ammonia (Scheme 62). Yields ranged from 81 to 91% at temperatures of 100-130 °C depending on the substrate (the aldehyde) employed. All the products obtained have the same structure except for the aromatic substituent in position 4 [109]. 

Mannich and related readions provide one of the most fundamental and useful methods for the synthesis of p-amino carbonyl compounds, which constitute various pharmaceuticals, natural products, and versatile synthetic intermediates.1271 Conventional protocols for three-component Mannich-type readions of aldehydes, amines, and ketones in organic solvents indude some severe side reactions and have some substrate limitations, espedally for enolizable aliphatic aldehydes. The dired synthesis of P-amino ketones from aldehydes, amines, and silyl enolates under mild conditions is desirable from a synthetic point of view. Our working hypothesis was that aldehydes could read with amines in a hydro-phobic reaction fidd created in water in the presence of a catalytic amount of a metal triflate and a surfactant to produce imines, which could then read with hydrophobic silyl enolates. 

The condensation between an aldehyde, an amine and an active methylene compound, named after Carl Mannich, was first published in 1912 [4]. The products of the reaction, a-amino ketones or Mannich bases are important compounds with numerous applications in the synthesis of pharmaceuticals and of natural products [7]. 

Several natural products and pharmaceuticals have been made in which a TRAP-catalysed oxidation of a primary alcohol to aldehyde step occnrs, and these are listed in 2.1.3 abscisic acid, altohyrtin A, (+)-arisngacin A, 14-[2H]-arteether (Fig. 2.4), astrogorgin, avermectin-Bla (Fig. 2.6), (H-)-batzelladine A (Fig. 1.13), brevetoxin B, (+)-catharanthin, ( )-epibatidine, 2-epibotcinolide, (-)-7-epicylin-drospermopsin, ( )-epimaritidine, epothilone C, irisqninone (Fig. 2.3), gambieric... 

Ethylene glycol in the presence of an acid catalyst readily reacts with aldehydes and ketones to form cyclic acetals and ketals (60). 1,3-Dioxolane [646-06-0] is the product of condensing formaldehyde and ethylene glycol. Applications for 1,3-dioxolane are as a solvent replacement for methylene chloride, 1,2-dichloroethane, 1,1,1-trichloroethane, and methyl ethyl ketone as a solvent for polymers as an inhibitor in 1,1,1-trichloroethane as a polymer or matrix interaction product for metal working and electroplating in lithium batteries and in the electronics industry (61). 1,3-Dioxolane can also be used in the formation of polyacetals, both for homopolymerization and as a comonomer with formaldehyde. Cyclic acetals and ketals are used as protecting groups for reaction-sensitive aldehydes and ketones in natural product synthesis and pharmaceuticals (62). 

The Henry reaction or the nitroaldol is a classical reaction where the a-anion of an alkyinitro compound reacts with an aldehyde or ketone to form a p-nitroalcohol adduct. Over the decades, the Henry reaction has been used to synthesize natural products and pharmaceutical intermediates. In addition, asyimnetric catalysis has allowed this venerable reaction to contribute to a plethora of stereoselective aldol condensations. Reviews (a) Ballini, R. Bosica, G. Fiorini, D. Palmieri, A. Front. Nat. Prod. Chem. 2005, 1, 37-41. (b) Ono, N. In The Nitro Group in Organic Synthesis Wiley-VCH Weinheim, 2001 Chapter 3 The Nitro-Aldol (Henry) Reaction, pp. 30-69. (c) Luzzio, F. A. Tetrahedron 2001, 57, 915-945. 

Propargylic amines are high value building blocks in organic synthesis, and the corresponding stractural motif has been found in various natural products, and in compounds of pharmaceutical or phytoprotective relevance. They can be obtained by addition of alkynes to imines, bnt since imines are easily formed from aldehydes and amines. 

Oxindoles with an all-carbon quaternary center at the C3 position are privileged structural motifs found in many pharmaceuticals and alkaloid natural products [90]. The asymmetric Michael addition of oxindoles proved to be an efficient method for the construction of these structural motifs and a wide range of electrophiles such as a,(3-unsaturated aldehydes [91], ketones [92], sulfones, nitroalkenes [93], and 2-chloroacrylonitrile [94] have been weU studied in recent years (Scheme 5.45). 

The amide group is an essential motif in biological systems as well as in important molecules in the areas of polymers, natural products, and pharmaceuticals. Direct amidation of aldehydes with amines is the most desired approach to amides because of economics and the availability of starting materials. Various efficient catalysts have been... 

Chain elongation and chain branching of aldehydes via C-C bond formation reactions initiated with a hydroformylation step are of huge synthetic value for the construction of bulk and fine chemicals. Especially in the last years, the total synthesis of natural products and pharmaceutically important compounds has benefited from these approaches. Different methodologies will be discussed in detail here. 

Asian J., 2, 820-827 (h) Rueping, M., Dufour, J., and Schoepke, F.R. (2011) Advances in catalytic metal-free reductions from bio-inspired concepts to application in the organocatalytic synthesis of pharmaceuticals and natural products. Green Chem., 13, 1084—1105 (i) Ebner, C. and Pfaltz, A. (2011) Chiral dihydrobenzo [l,4]oxazines as catalysts for the asymmetric transfer-hydrogenation of a, 3-unsaturated aldehydes. Tetrahedron, 67, 10287-10290. 

Stereodefined alkenes are ubiquitous structural motifs in many natural products and pharmaceutics, and, moreover, they serve as a foundation for a broad range of chemical transformations. Nowadays, carbonyl olefination, elimination, alkyne addition, alkenylation, and alkene metathesis constitute the most widely used methods for the stereoselective synthesis of various alkenes [1-3]. Whereas no single method provides a universal solution to stereoselective alkene synthesis, the olefination reactions of aldehydes and ketones with phosphorus-stabilized carbon nucleophiles have enjoyed widespread prominence and recognition owing to their simplicity, convenience, complete positional selectivity, and generally high levels of geometrical control [4-9]. 

One of the most important transition-metal-catalyzed reactions is the hydroformylation of alkenes around 8 million tons of aldehydes and associated products are synthesized each year using Rh- or Co-catalyzed hydroformylation in the commodity chemicals industry. Linear aldehydes and alcohols created in this manner are employed in the synthesis of many polymers, detergents, plastics, cosmetics, and other common products, and as a result of this, most of the research conducted over the past several decades has focused on the requirements of these processes. Significantly less work has been carried out on asymmetric hydroformylation of alkenes. However, this is an extremely efficient and atom-economic reaction, of emerging utility, which can deliver high-value products essential for the synthesis of natural products and pharmaceuticals. 

As a constituent of various pharmaceuticals, natural products, and versatile synthetic intermediates, a-amino carbonyl compounds are very important, which can be synthesized by Marmich-type reactions. Sc(DS)j was found to catalyze the three-component Mannich-type reaction of aldehydes 9, amines 14, and silyl enolates 15 in water [27b]. Another LASC, Cu(DS) 17, gave higher yield in this case (Scheme 8.6). 

Some chiral phase-transfer catalysts can also promote enantioselective aldol and Mannich condensations of glycine imine donors with aldehyde and imine acceptors. These reactions provide important tools for the asymmetric constmction of P-hydroxy-a-amino acid and a,p-diamino acid derivatives, which are extremely interesting chiral units in the synthesis of pharmaceutical and natural products. For... 

The synthesis of aldehydes via hydroformylation of alkenes is an important industrial process used to produce in the region of 6 million tonnes a year of aldehydes. These compounds are used as intermediates in the manufacture of plasticizers, soaps, detergents and pharmaceutical products [7], While the majority of aldehydes prepared from alkene hydroformylation are done so in organic solvents, some research in 1975 showed that rhodium complexes with sulfonated phosphine ligands immobilized in water were able to hydroformylate propene with virtually complete retention of rhodium in the aqueous phase [8], Since catalyst loss is a major problem in the production of bulk chemicals of this nature, the process was scaled up, culminating in the Ruhrchemie-Rhone-Poulenc process for hydroformylation of propene, initially on a 120000 tonne per year scale [9], The development of this biphasic process represents one of the major transitions since the discovery of the hydroformylation reaction. The key transitions in this field include [10] ... 

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