Chiral natural products synthesis

One of the first enantioselective transition metal-catalyzed domino reactions in natural product synthesis leading to vitamin E (0-23) was developed by Tietze and coworkers (Scheme 0.7) [18]. This transformation is based on a Pdn-catalyzed addition of a phenolic hydroxyl group to a C-C-double bond in 0-20 in the presence of the chiral ligand 0-24, followed by an intermolecular addition of the formed Pd-spe-cies to another double bond. 

The domino process probably involves the chiral enamine intermediate 2-817 formed by reaction of ketone 2-813 with 2-815. With regard to the subsequent cy-doaddition step of 2-817 with the Knoevenagel condensation product 2-816, it is interesting to note that only a normal Diels-Alder process operates with the 1,3-bu-tadiene moiety in 2-817 and not a hetero-Diels-Alder reaction with the 1-oxa-l,3-butadiene moiety in 2-816. The formed spirocydic ketones 2-818/2-819 can be used in natural products synthesis and in medidnal chemistry [410]. They have also been used in the preparation of exotic amino adds these were used to modify the physical properties and biological activities of peptides, peptidomimetics, and proteins... 

The reduction of nitro ketones with baker s yeast is a good method for the preparation of chiral nitro alcohols.89 The reduction of 5-nitro-2-pentanone with baker s yeast gives the corresponding (5)-alcohol, which is an important chiral building block. Various chiral natural products are prepared from it. In Scheme 7.16, the synthesis of the pheromone of Andrena haemorrhoa is described, where the acylation of the chiral nitro alcohol followed by radical denitration is involved as key steps.89a... 

Keywords Asymmetric Catalysis a Natural Product Synthesis a Chiral Metal-Based Complexes a Enantioselective C-C Bond Formation a Enantioselective C-O Bond Formation... 

Gerard Uhommet was born in 1945 in Paris (France). He obtained his M.Sc. from the University of Paris in 1969. He carried out his Ph.D. studies under the supervision of Profs Pierre Maitte and Henri Sliwa at UPMC (P. and M. Curie University), Paris between 1970 and 1975. After a postdoctoral position at the East Anglia University in Norwich, UK, with Prof A.R. Katritzky (1976-1977), he accepted a position as Assistant Professor at UPMC, Paris. In 1985, he became Full Professor at the same university. His research interests include the development of new strategies sparing chiral auxiliaries for use in asymmetric and natural product synthesis. 

The addition of an enolsilane to an aldehyde, commonly referred to as the Mukaiyama aldol reaction, is readily promoted by Lewis acids and has been the subject of intense interest in the field of chiral Lewis acid catalysis. Copper-based Lewis acids have been applied to this process in an attempt to generate polyacetate and polypropionate synthons for natural product synthesis. Although the considerable Lewis acidity of many of these complexes is more than sufficient to activate a broad range of aldehydes, high selectivities have been observed predominantly with substrates capable of two-point coordination to the metal. Of these, benzy-loxyacetaldehyde and pyruvate esters have been most successful. 

The regio- and stereo-selective functionalization of aldonolactones yields optically active lactones, which are important precursors in natural product synthesis. Concepts such as chiral templates and chirons, derived from carbohydrates, have been ingeniously and widely applied in synthesis (233). Among the commercially available aldonolactones, D-ribono-1,4-lactone is... 

A bromoallene 75 was prepared from 74 following the standard procedure and used in the natural product synthesis [31] of 78 (Scheme 4.19) [32]. Crimmins and Emmitte succeeded in the construction of the chiral bromoallene moiety of isolaur-allene 83 by bromination of propargyl sulfonate 81 with LiCuBr2 as a key step (Scheme 4.20) [33] (cf. Section 18.2.3). 

The first chapter in this volume is a particularly timely one given the recent surge of activity in natural product synthesis based upon stereocontrolled Aldol Condensations. D. A. Evans, one of the principal protagonists in this effort, and his associates, J. V. Nelson and T. R. Taber, have surveyed the several modem variants of the Aldol Condensation and discuss models to rationalize the experimental results, particularly with respect to stereochemistry, in a chapter entitled Stereoselective Aldol Condensations. The authors examine Aldol diastereoselection under thermodynamic and kinetic control as well as enantioselection in Aldol Condensations involving chiral reactants. 

N-Boc-N-(but-2-enoyl)amine is an excellent pronucleophile for the Ir-catalyzed allylic amination under salt-free conditions (cf. Table 9.3, entries 15-18). The products were subjected to RCM with good results, even upon application of the Grubbs I catalyst (Scheme 9.29) [27bj. The resultant N-Boc protected a,P-unsaturated y-lactams are valuable chiral intermediates with appUcations in natural products synthesis and medicinal chemistry. 

Keywords a-Hydroxylated lignans Natural product synthesis Enantioselective hydrogenation Chiral building blocks Malic acid... 

Non-racemic a-substituted allylic silanes, in particular crotylsilanes, are very attractive reagents despite their rather tedious preparation. They were found to provide very high transfer of chirality in their additions to achiral aldehydes under Lewis acid catalysis (Eq. 114). These reagents have been tested several times in the context of natural product synthesis. Their diastereoselectivity (syn/anti) depends on several factors, including the natme of the aldehyde substrate, the reagent, and the natme of the Lewis acid employed. For example, the syn product can be obtained predominantly in the reaction of Eq. 114 by switching to the use of a monodentate Lewis acid such as BF3. 

This chapter is divided into four major sections. The first (Section 2.1) will deal with the structure of both alkoxy and silyl nitronates. Specifically, this section will include physical, structural, and spectroscopic properties of nitronates. The next section (Section 2.2) describes the mechanistic aspects of the dipolar cycloaddition including both experimental and theoretical investigations. Also discussed in this section are the regio- and stereochemical features of the process. Finally, the remaining sections will cover the preparation, reaction, and subsequent functionalization of silyl nitronates (Section 2.3) and alkyl nitronates (Section 2.4), respectively. This will include discussion of facial selectivity in the case of chiral nitronates and the application of this process to combinatorial and natural product synthesis. 

The same authors 83) used the chiral ketone (46) as substrate for the preparation of optically active cyclohexanol derivatives (47) which may be useful intermediates in the synthesis of chiral natural products, such as (—)-mesenbranoene, (+)-2-carene etc. 

As already demonstrated in the previous natural product synthesis, the alkylation of 2,2-dimethyl-l,3-dioxan-5-one SAMP/RAMP hydrazones is a reliable tool with which to synthesize chiral 4-substituted 2,2-dimethyl-l,3-dioxan-5-ones in gram quantities and with high enantiomeric excesses [68]. Thus, after metalla-tion of the RAMP hydrazone (R) -96 the corresponding lithio azaenolate was alkyl-... 

Cyclo-addition is used extensively in the synthesis of chiral natural products and pharmaceutical agents, because the reaction can determine the relative configuration of up to four chiral centres in a single reaction. 

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