New strategy in organic synthesis

In the total synthesis of optically active erythromycin A reported by Woodward and collaborators (87), the bicyclic compound 142 (Fig. 1) was used to produce the two segments Cg-C g (143) and C3 —Cg (144) of erythronolide A. These two segments were then combined ( 145) and converted into 146). Aldol condensation of a propionate ester derivative with gave the erythronolide A secoacid derivative 147 (Fig. 2) which was successfully transformed into erythromycin A (149) through a series of chemical transformations where compound 148 was one of the key intermediates. 

A new strategy for the synthesis of erythromycin A and closely related mac-rolide antibiotics was elaborated in our laboratory (88). This new approach to synthesis is based on the knowledge that stereoelectronic effects control the conformation of acetals. The strategy is based on the 1,7-dioxaspiro-[5.5]undecane system which was found to be conformationally rigid, existing in conformation 150 only (see Chapter 2). This is so because in thisconfor-mation, steric effects are at their minimum and the acetal function has 

Compound 160 was then transformed into the conjugated enone 161. Lithium dimethylcopper 1,4-addition on enone 161 and reaction of the resulting enolate with dibenzoyl peroxide gave compound 62 in good yield. Reaction of 162 with methylmagnesium iodide at low temperatures furnished compound 163 again in good yield. Thus by this sequence, an excellent control of 

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The development of new strategies in organic synthesis with a minimum of chemical steps has become more and more necessary for the efficient creation of complex molecular structures. The ability of palladium(O) catalysts to exercise control in bond forming has made it an excellent candidate for the synthesis of biologically active molecules. Allylic alkylations catalyzed by palladium have widely been studied and have proved unusually productive because of the extraordinary chemo-, regio-, and diastereoselectivity and the continuing possibility for the development of enantioselectivity. 

The tricyclic sesquiterpene longifolene has served as a vehicle for the illustration of new strategies for organic synthesis.25 Both enantiomers have been obtained from natural sources (-i-)-longifolene occurs in several Firms species and is commercially available while the rare (—)-longifolene has been found in certain liver mosses.2 We elected to prepare (—)-longifolene 49 from the cyclohexa-1,4-diene 45, obtained from the Birch reduction-alkylation of benzoxazepinone 9 in 96% yield with a diastereomeric excess of greater than 98% (Scheme 13).22... 

Review D. Hoppe and O. Zschage, Chiral metaUated carbamates Tools for new strategies in asymmetric synthesis , in Organic Synthesis via Organometallics (Eds. K. H. Ddtz and R. W. Hoffmann), Vieweg, Braunschweig, 1990, pp. 267-284. 

Selected recent developments in the area of asymmetric organocatalysis in our laboratory have been briefly summarized. Enamine catalysis, Brpnsted acid catalysis, and iminium catalysis turn out to be powerful new strategies for organic synthesis. Using Hantzsch ester as the hydride source, highly enantioselective transfer hydrogenantion reactions have been developed. We have also developed an additional new con-... 

The search for new selective synthons is an important area in organo-fluorine chemistry.1 4 In recent years organosilicon chemistry has become important in the development of new methodologies in organic synthesis.5-8 Anionic activation of tetracoordinate organosilicon species has been utilized for a variety of C —C and carbon heteroatom bond formation strategies in syntheses of highly fluorinated materials.9 13... 

C-H and C-C bond activations by ruthenium complexes have formed the focus of this chapter, and consequently other important reactions to cleave chemical bonds such as dihydrogen, C-S and M-R have not been described. Today, ruthenium is regarded as a powerful tool for cleaving a variety of both activated and unactivated chemical bonds under homogeneous conditions. Important factors that provide these activities include 1) coordinative unsaturation of the ruthenium center 2) a close proximity of the bond to the ruthenium metal and 3) kinetic preference and thermodynamic stability of the products. It is likely that the combined use of ruthenium complexes and modern strategies in organic synthesis and catalysis will provide many opportunities for the creation of new reaction processes in the futtue. 

The basis on which all strategies in organic synthesis are founded are the individual synthetic reactions. An overall plan for the construction of a complex target molecule may be ingenious and elegant, but it is sufficient that one single step fails for the whole plan to fail. To develop new reactions or to develop known reactions into reliable and efficient synthetic methods is therefore crucial to the art and science of organic synthesis. 

With directed evolution we can engineer enzyme properties rapidly and with a high probability of success. Many enzymes that have been improved by directed evolution are listed in Tab. 4-3. This powerful biocatalyst engineering strategy creates new opportunities in organic synthesis new and improved bioconversion processes can be developed and novel compounds that are otherwise inaccessible by classical chemistry can be synthesized. In addition, the molecules created by directed evolution offer an excellent opportunity for improving our still poor understanding of sequence-structure-function relationships. 

Hoppe D, Zschage O (1990) Chiral metallated carbamates Tools for new strategies in asymmetric synthesis. In Dotz KH, Hoffmann RW (eds) Organic synthesis via organo-metallics, 1st edn. Vieweg, Braunschweig, p 267... 

Double asymmetric synthesis and a new strategy for stereochemical control in organic synthesis [95]... 

Parsons, P.J., Penkett, C.S., Shell, A.J. (1996) Tandem Reactions in Organic Synthesis Novel Strategies for Natural Product Elaboration and the Development of New Synthetic Methodology. Chemical Reviews, 96, 195-206. 

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