Application in Organic Synthesis

The methods described above are very well suited for applications in syntheses of biologically active compounds, in particular N-heterocycles such as alkaloids. Generally, the Ir-catalyzed allylic substitution is particularly well suited for 

Allylic Substitution in Combination with Ring Closing Metathesis 

The combination of an allylic substitution and an RCM [21] constitutes a powerful approach for syntheses of carbo- and heterocycles this approach was 

The first example of asymmetric thio-Claisen rearrangement based on axial chirality has been described by our group and involves atropisomeric thioanilides bearing an ortbo-tert-butyl group [132]. These axially chiral thioamides were subjected to LDA deprotonation followed by S-allylation with various allyl halides. 

A number of sulfurated heterocycles can be prepared using this transposition. The principal synthetic routes have been already surveyed in previous reviews [38,40). 

Nickel-catalyzed hydroalumination has found some specific applications in organic synthesis (see below). 

The reaction may proceed via the hydroalumination of the olefin moiety to give 15, which can undergo [3-alkoxy elimination to yield, upon workup, the alcohol 16. How- 

The presence of a free hydroxyl group is not a requirement for high selectivity, as demonstrated by the reductive ring opening reaction of the methyl and TBDMS 

Reductive ring-opening reactions A very useful application of a transition metal at- 

The reactions of carbodiimides outlined in Section 2.4 demonstrate the use of carbodiimides in organic synthesis. In the current chapter only some of the more important applications 

In view of the rapid reaction of carbodiimides with water they are often used in dehydration reactions. Major examples are the intra- and intermolecular esterification reactions of carboxylic acids, and the formation of peptides from carboxylic acids and protected amino acids. Especially, dicyclohexylcarbodiimide (DCC) or diisopropylcar-bodiimide (DIPCD) are often used in carbodiimide mediated reactions because the corresponding urea byproducts are insoluble in most organic solvents and water, and therefore are readily removed by filtration. Also, water soluble carbodiimides, such as N-ethyl-N -(3-dimethylamino)propylcarbodiimide (EDC) or its hydrochloride (EDCCl, sometimes referred to as EDAC) are often used in these reactions. EDC reacts with carboxyl groups at pH of 4.0-6.0, but loses its reactivity at lower pH. Sometimes solid phase reactions are conducted using carbodiimide terminated linear or crosslinked polymers. 

Carbodiimides also play a role as building blocks of numerous N-heterocycles. Examples are the cycloaddition reactions of carbodiimides. In the formation of [2-1-2] cycloadducts N-methyl-N -t-butylcarbodiimide is used as a marker to determine the mode of addition of isocyanates or isothiocyanates to carbodiimides. In these reactions addition across the C=N or the C=0 bond of the isocyanate or across the C=N or the C==S bond of the isothiocyanate can occur. Addition to the N-methyl-N -t-butylcarbodiimide always proceeds across the N-methyl double bond. Also, theretroreaction of the [2-1-2] cycloaddition reaction of carbodiimides can afford a different set of heterocumulenes.  

Carbodiimides are also excellent dipolarophiles in [2-1-3] cycloaddition reactions. For example, 1,2,3,4-tetrazolium salts are obtained from dialkylcarbodiimides and 1,3-diaza- 

An important reaction of carbodiimides leading to bicycUc N-heterocycles is the aza-Wittig reaction. Often carbodiimides with unsaturated substituents are generated in situ and subsequent cyclization reactions afford the N-heterocycles. Many of these reactions are reported by Molina, Saito ° and Wamhoff. In the aza-Wittig reaction iminophosphoranes react with heterocumulenes (CO2, CS2, RNCO and RNCS) to generate carbodiimides, which often undergo subsequent reactions. 

The Lewis acid-catalyzed Fries rearrangement is performed under strong acidic conditions and therefore reqnires protection of sensitive functional groups. Conversely, the PFR can be achieved nnder milder conditions (organic solvents, nentral media, room temperature, etc.) and is therefore free from this type of problems. Moreover, polyacylation of aromatics is usually difficult to achieve. In the PFR, this problem can be solved by using acetals [144—146] or enol esters [147] as carbonyl protecting groups. Addition of anhydrous K CO is convenient to avoid deprotection [148]. 

Substituted tetrahydroisoquinolines have been obtained by PFR of appropriate 4-methoxyphenylacetates, followed by tandem rednction/cyclization and further reduction. The 

SCHEME 31.16 Synthesis of xanthones by PER of salicylic or thiosaUcylic acid phenyl esters. 

SCHEME 31.17 Photorearrangement of a macrocycUc lactone as a step in the total synthesis of (-)-kendomycin. 

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Augustine, R. L. 1965, Catalytic Hydrogenation Techniques and Applications In Organic Synthesis, M. Dekker New York... 

Augustine, R. L. Trecker, D. J. 1971, Oxidation Techniques and Applications in Organic Synthesis, Vol. 

R. L. Augustine, Catalytic Elydrogenation, Techniques and Applications in Organic Synthesis Series, Vol. 1, Marcel Dekker Inc., New York, 1965. 

From this research has come a wealth of procedures which potentially should have wide application in organic synthesis. Indeed, many have already been widely exploited. 

Trimethylsilyl trifluoromethanesulfonate (trimethylsilyl triflate) is the most synthetically useful representative of the family of trialkylsilyl perfluoroalkane-sulfonates (for a review, see reference 101) This reagent is commercially available or can be prepared easily by the reaction of chlorotrimethylsilane and triflic acid [101] It has wide application in organic synthesis as an excellent silylating reagent... 

Another triflate ester that recently has found growing application in organic synthesis is commercially available trimethylsilylmethyl trifluoromethanesul fonate. This powerful alkylating reagent can be used for the synthesis of various methylides by an alkylation-desilylation sequence A representative example is the generation and subsequent trapping by 1,3-dipolar cycloaddition of indolium methanides from the corresponding indole derivatives and trimethylsilylmethyl trifluoromethanesulfonate [108] (equation 54)... 

Application in organic synthesis of optically active isoxazolidones obtained by asymmetric cycloaddition of nitrones with allenes 97T403. 

All three coupling procedures are suitable to give high yields under mild reaction conditions. Many functional groups do not interfere. For the application in organic synthesis the Eglinton variant may be more convenient than the Glaser method a drawback however is the need for stoichiometric amounts of copper salt. 

The nitro-dldolredcdon between nitrodlkdnes and carbonyl compounds to yieldfi-nitro alcohols was discovered in 1895 by Henry. Since dien, diis reaction has been used extensively in many important syndieses. In view of its significance, diere are several reviews on die Henry reaction." These reviews cover syndiesis of fi-nitro alcohols and dieir applications in organic synthesis. The most comprehensive review is Ref 3, which summarizes the literature before 1970. More recent reviews are Refs. 4 and 5, which summarize literatures on the Henry reaction published until 1990. 

For former reviews on parts of the topic, see Refs. [10-12]. The subject is increasingly attractive and has now far-reaching applications in organic synthesis and supramolecular chemistry. 

Arylmetallic compounds have various, but not very widely used, applications in organic synthesis. Examples are acyl-de-metallation reactions using either dicobalt octacarbonyl in tetrahydrofuran (Seyferth and Spohn, 1969 Scheme 10-92), or carbon monoxide and a rhodium catalyst (Larock and Hershberger, 1980). 

Photo-de-diazoniation has found relatively little application in organic synthesis, as is clearly evident from the annual Specialist Periodical Reports on Photochemistry published by the Royal Society of Chemistry. Since the beginning of these reports (1970) they have contained a section on the elimination of nitrogen from diazo compounds, written since 1973 by Reid (1990). In the 1980s (including 1990), at least 90% of each report is concerned with dediazoniations of diazoalkanes and non-quinon-oid diazo ketones, the rest being mainly related to quinone diazides and only occasionally to arenediazonium salts. 

Abstract For many years after its discovery, olefin metathesis was hardly used as a synthetic tool. This situation changed when well-defined and stable carbene complexes of molybdenum and ruthenium were discovered as efficient precatalysts in the early 1990s. In particular, the high activity and selectivity in ring-closure reactions stimulated further research in this area and led to numerous applications in organic synthesis. Today, olefin metathesis is one of the... 

Although the number of applications of olefin metathesis to transition metal complexes is small compared to the number of applications in organic synthesis, this field is becoming increasingly important. Spectacular examples are the double RCM reactions of copper phenanthroline complexes as a synthetic route to catenanes [113] or a recently reported approach to steric shielding of rhenium complex terminated sp-carbon chains [114]. 

Dihydro-1-vinylnaphthalene (67) as well as 3,4-dihydro-2-vinylnaphtha-lene (68) are more reactive than the corresponding aromatic dienes. Therefore they may also undergo cycloaddition reactions with low reactive dienophiles, thus showing a wider range of applications in organic synthesis. The cycloadditions of dienes 67 and 68 and of the 6-methoxy-2,4-dihydro-1-vinylnaphthalene 69 have been used extensively in the synthesis of steroids, heterocyclic compounds and polycyclic aromatic compounds. Some of the reactions of dienes 67-69 are summarized in Schemes 2.24, 2.25 and 2.26. In order to synthesize indeno[c]phenanthrenones, the cycloaddition of diene 67 with 3-bromoindan-l-one, which is a precursor of inden-l-one, was studied. Bromoindanone was prepared by treating commercially available indanone with NBS [64]. 

Wong HNC Regiospecific Synthesis of Polysubstituted Furans and Their Application in Organic Synthesis Pure Appl. Chem. 1996 68 335 344... 

The first chapter presents the general aspects of the reaction Chapters 2-6 illustrate the various methods and their applications in organic synthesis. At the end of each chapter a list of graphically abstracted Diels-Alder reactions is presented to show selected synthetic applications of the specific methodology. The discussion of the various topics is not exhaustive because our aim has been to emphasize the synthetic potential of each method. Chapter 7 reports a list of books, reviews, monographs and symposia proceedings which have appeared since 1990 and an index of keywords to help the reader find a particular paper of interest. 

Kolodiazhnyi 01 (1999) Phosphorus ylides chemistry and application in organic synthesis. Wiley-VCH, p 73... 

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