Synthetic Aspect

Synthetic Aspects.—Continuing interest has been shown in the use of norbomene derivatives, produced by Diels-Alder reactions, for t ie synthesis of carbocyclic analogues of C-nucleosides.  

The bicyclo[2,2,l]heptane system also continues to find employment for the assessment of new synthetic procedures, or for testing the efficacy of new reagents. Isolated yields of 50—65 % of ap-unsaturated aldehydes have been obtained by reaction of alkyl tosylhydrazones with butyl-lithium, addition of DMF, and hydrolysis however, reaction of camphor tosylhydrazone (381 X = NNHTs) according to this procedure only gave 10 % of the aldehyde (382 X = CHO), presumably because of unfavourable steric effects. Trimethylsilyl trifluoromethanesulphonate is a mild reagent for converting carbonyl compounds into trimethylsilyl enol ethers, for example the production of (382 X = OSiMcj) from camphor (381 X = Experimental details 

Simple syntheses of ( )-phyllostine (384), ( )-epoxydon (385), and (+ )-epiepoxy-don (386) have been accomplished starting from either the exo- or endo-[A + 2] adducts of p-benzoquinone with 6,6-dimethylfulvene. Thus, for example, epoxida-tion of the endo-adduct gave (387) which, on treatment with formalin in the presence of diazabicycloundecene in THF at 0°C, gave (388). Pyrolytic retro-[4 + 2] reaction of (388) afforded (384), whilst partial reduction of (387) followed by hydrcxymethyla-tion and retro-Diels-Alder reaction gave (385) a similar sequence of reactions yielded (386) from the exo-adduct. 

Reader, and B. Chalard-Faure, Canad. J. Chem., 1976,54,849 G. Just and B. Chalard-Faure, ibid., p. 861. 

The Diels-Alder adduct (389), on sequential hydrolysis, bromolactonization, and reductive debromination, was converted into the hydroxy-lactone (390), which, on Collins oxidation to (391) and Baeyer-Villiger ring-expansion, afforded the novel dilactone (392). Free-radical cyclization of the bromo-ketone (393), initiated by tri-n-butyltin hydride, gave a 3 2 mixture of the endo- and exo-derivatives (394), which, on separation and homologation, were transformed into the tricyclic sesquiterpenes sativene, endo-(395), and copacamphene, exo-(395). The use of bicyclo- 

Synthetic Aspects.— The extraction of reaction mixtures with aqueous sodium hydrogen sulphite has been advocated as a mild procedure for the efficient removal of norbornenone and norbornenol impurities.Deuteriated olefins can be efficiently synthesized from the corresponding arenesulphonylhydrazones. The reaction of R R CHC(R ) NNHS02Ar with an alkyl-lithium in tetramethylethylenediamine produces R R C (CR which, upon quenching with water (or D 2 O), is converted into olefin R R C=CHR (or R R C=CDR ). Treatment of the sulphonylhydrazone derived from camphor by this method gave (442) in quantitative yield with a 95 % [ H2] analysis.  

The intramolecular capture of the homoallylic 5-norbornen-2-yl cation by an alkynyl substituent, as exemplified by the sequence (443)- (444)- (445)- (446), has been used to advantage in a stereospecific synthesis of rf,/-cyclosativene (448). Treatment of the tosylate ester (443 R = Me, X = OTs), prepared in several steps from l,2-dimethylcyclopenten-3-ol, with pyridine in trifluoroethanol solution gave the vinyl ether (447) which was transformed by several more steps into (448).  

The synthesis of (+ )-sesquifenchene (450) and of ( )-epi-P-santalene (451) from the common intermediate (449), derived from endo-dicyclopentadiene, has been detailed. Conversion of (449) into the precursor of (450) makes use of the skeletal rearrangement that occurs during solvolysis of active 2-norbornyl esters. In a synthesis of (-H )-hinesol (452) and 10-epi-(-l-)-hinesol, interesting use has been made of a fragmentation reaction.The tosyl derivative (453), which was obtained in several steps from ( —)-P-pinene, was converted into the spiro[4,5]decane (455) on treatment with sodium hydride in DMSO the essential stereoelectronic changes are summarized in the intermediate (454). 

Treatment of 3,3-dibromocamphor with bromine and chlorsulphonic acid (conditions under with 3,3,8-tribromocamphor is formed), followed by working-up the crude reaction mixture with zinc and hydrobromic acid to effect selective debromination, provided 8-bromocamphor (456) in a regiospecificprocess. Prolonged treatment of c(,/-camphor with excess BF3, OEt2 and ethyl diazoacetate in ether afforded a 2 1 mixture (63 % yield) of the camphene derivatives (457) and (458). Reaction of the mixture with zinc dust and glacial acetic acid at reflux gave (457) in essentially quantitative yield from (458).  

Diels-Alder addition of tetrachlorocyclopentadiene dimethylketal to endo-5-norbornene carboxylic acid produces (459). Ketal cleavage (H2SO4), cheletropic loss of CO (reflux in o-dichloro benzene), and aromatization (bromine in hot chlorobenzene) affords the endo-acid (460 X = Cl) which can be dechlorinated by reaction with Ni-Al alloy and alkali to give (460 X = H). The clean retention of stereochemistry in reaction sequence is suggested to be of value in the general synthesis of alicyclic-substituted benzonorbornenes the methyl ester of (460 X = H) can likewise be prepared without epimerization.  

Only a few reactions, of outstanding utility or special mechanistic interest, can be mentioned here. 

Cleavage of spirooxiranes e.g. 59) by thiophenol is a key step in a new route to -fused 

Oxirane opening by functionalized ethenylaluminum (81JA1851) and ethenylcopper (79JCS(Pl)2954) reagents has found applications in natural products synthesis. 

Oxiranes undergo Friedel-Crafts reactions (64HC(19-1)432) but these do not appear to be synthetically useful. 

Cyclization of polyenes by intramolecular rr-attack on an oxirane is an important biochemical reaction (Section 5.05.5.2). 

If metal ions in solution are reduced to atoms by an appropriate redudng agent, they normally will combine into colloids or into microcrystalline particles which finely predpitate out. Such processes can occur within seconds, as is known for instance from the formation of silver mirrors on glass by the reduction of silver ions. If the growth of the metal particles in solution can be retarded and if appropriate ligands are additionally offered, it may happen that metal rich ligand stabilized transition metal clusters of uniform rize are formed. 

In prindple, the synthesis of such dusters could also succeed by the degradation of bulk particles, however, the experimental difficulties assodated with this suggest the opposite way is better, namely to form dusters by the building up from atoms. It should be mentioned that up to now it doesn t seem possible to synthesize clusters with the aim of adueving a particular result. What matters is to find out the appropriate reaction conditions to generate, for example, a SS atom or a 561 atom cluster. 

The formation of dusters finm atoms and their subsequent stabilization with ligands, in our case we consider mainly phosphorus and nitrogen containing molecules, is accompanied by a surprising phenomenon most of the dusters obtained by this method have a so-called full shell structure. This means that the 

2 The Characterization of Lai e Clusters hy High Resolution li ansmission Electron Microscopy (HRTEM) and by Scanning Ihnneling Microscopy (STM) 

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Important synthetic aspects in such olefinations of carbonyl compounds are... 

Rossiter, B. E. 1985, Synthetic Aspects and Applications of Asymmetric Epoxidation, in Morrison, J. D. 

Tri- and pentacoordinate phosphoms compounds often react by electron-pair mechanisms as demonstrated by the nucleophilic reactivity of the lone pair electrons in trivalent compounds, and the electrophilicity of the phosphoms atom in the pentavalent compounds. Some compounds also react by free-radical mechanisms. The theoretical and synthetic aspects of the chemistry of phosphoms compounds have been described (6—9). 

A number of general reviews related to the topics covered in this chapter have appeared (Table 1) and others will be discussed in the section dealing with synthetic aspects (Section 4.04.3.1). The Sokolov review is particularly noteworthy since it is quite recent and complete, containing 304 references to pyrazoles and isoxazoles. 

Electrophilic aromatic substitution reactions are important for synthetic purposes and also are one of the most thoroughly studied classes of organic reactions from a mechanistic point of view. The synthetic aspects of these reactions are discussed in Chapter 11 of Part B. The discussion here will emphasize the mechanisms of several of the most completely studied reactions. These mechanistic ideas are the foundation for the structure-reactivity relationships in aromatic electrophilic substitution which will be discussed in Section 10.2... 

The primary objective of this review is to provide an integrated analysis of the contributions from structural, mechanistic and preparative studies toward the successful development of a modern, stereoselective reaction. The synthetic aspects of this useful transformation have been extensively reviewed elsewhere [6]. 

The catalytic enantioselective cycloaddition reaction of carbonyl compounds with conjugated dienes has been in intensive development in recent years with the main focus on synthetic aspects the number of mechanistic studies has been limited. This chapter will focus on the development and understanding of cycloaddition reactions of carbonyl compounds with chiral Lewis acid catalysts for the preparation of optically active six-membered ring systems. 

In this book we have decided to concentrate on purely synthetic applications of ionic liquids, just to keep the amount of material to a manageable level. FFowever, we think that synthetic and non-synthetic applications (and the people doing research in these areas) should not be treated separately for a number of reasons. Each area can profit from developments made in the other field, especially concerning the availability of physicochemical data and practical experience of development of technical processes using ionic liquids. In fact, in all production-scale chemical reactions some typically non-synthetic aspects (such as the heat capacity of the ionic liquid or product extraction from the ionic catalyst layer) have to be considered anyway. The most important reason for close collaboration by synthetic and non-synthetic scientists in the field of ionic liquid research is, however, the fact that in both areas an increase in the understanding of the ionic liquid material is the key factor for successful future development. 

R. Spitz, Recent Advances in Mechanistic and Synthetic Aspects of Polymerization, Reidel Publishing Co., Japan, p. 485 (1987). 

This article, while not being intended to provide a full account of poly(arylene)s, emphasises the synthetic aspects. The synthesis of conjugated oligomers and polymers is, however, always part of an interdisciplinaiy approach with their active physical function being a key concern. In that sense the research being reviewed above concentrates on physical properties rather than playing with exotic chemical structures. 

Diisobutylaluminum hydride (DIBAL-H) can also be used for partial reduction of cyclic imides37. Although less convenient than sodium borohydride, an important synthetic aspect is the fact that in the reduction of asymmetrically substituted imides, diisobutylaluminum hydride and sodium borohydride may show opposite regioselectivity38,39. 

Synthetic aspects of Cu—Mo—S systems and their possible relevance to copper-molybdenum antagonism. S. Sarker and S. B. S. Mishra, Coord. Chem. Rev., 1984,59, 239-264 (80). 

The synthetic aspects of this acid-catalyzed process have been studied extensively for many years, and they have been reviewed recently by Falbe (1970). The kinetic and thermodynamic details of the various reaction steps in the overall process have been investigated in this laboratory during the last few years with special emphasis on the carbonylation step. The present article reflects the state of affairs in this respect. 

Nagata, W. "Synthetic Aspects of 1-Oxacephem Antibiotics , in Curr. Trends Org. Synth., Proc. Int. Conf, 4th, Tokyo, 22.-27.8.1982 Ed. by H. Nozaki Pergamon Press 1983. 

Solid Phase Biochemistry Analytical and Synthetic Aspects. 

Abstract Recent advances in synthetic aspects of the rhodium-catalyzed hydroformylation of alkenes are reviewed. Emphasis is given to practical improvements, efficient new catalysts for regioselective and enantioselective hydroformylation, and to applications of the reaction in organic synthesis. Furthermore, new developments in directed hydroformylation are covered as well as new approaches toward efficient hydroformylation catalysts employing the concept of self-assembly. 

Synthetic Aspects of Electrohydrogenation of Nitro Compounds at Raney Metal (RM) Electrodes in Aqueous Alcohols... 

Vol. 66 Solid Phase Biochemistry Analytical and Synthetic Aspects. Edited by William H. Scouten Vol. 67 An Introduction to Photoelectron Spectroscopy. By Pradip K. Ghosh Vol. 68 Room Temperature Phosphorimetry for Chemical Analysis. By Tuan Vo-Dinh Vol. 69 Potentiometry and Potentiometric Titrations. By E. P. Serjeant Vol. 70 Design and Application of Process Analyzer Systems. By Paul E. Mix Vol. 71 Analysis of Organic and Biological Surfaces. Edited by Patrick Echlin Vol. 72 Small Bore Liquid Chromatography Columns Their Properties and Uses. Edited by Raymond P.W. Scott... 

Aromatic nitro compounds undergo nucleophilic aromatic substitutions with various nucleophiles. In 1991 Terrier s book covered (1) SNAr reactions, mechanistic aspects (2) structure and reactivity of anionic o-complexes (3) synthetic aspects of intermolecular SNAr substitutions (4) intramolecular SNAr reactions (5) vicarious nucleophilic substitutions of hydrogen (VNS) (6) nucleophilic aromatic photo-substitutions and (7) radical nucleophilic aromatic substitutions. This chapter describes the recent development in synthetic application of SNAr and especially VNS. The environmentally friendly chemical processes are highly required in modem chemical industry. VNS reaction is an ideal process to introduce functional groups into aromatic rings because hydrogen can be substituted by nucleophiles without the need of metal catalysts. 

Ballard DG, Holmes PA, Senior PJ (1987) Recent advances in mechanistic and synthetic aspects of polymerization. Reidel Publishing... 

In a second paper from Kirillov et al., synthetic aspects of liquid phase precipitation reactions are discussed in relation to the factors responsible for metal-oxide formation. In particular the Pechini reaction, a sol-gel process, was examined. A good reference section is provided to introduce the reader to previous literature. The authors stress that more work needs to be done to establish what factors are important for producing the highest quality metal-oxide powders from such reactions. The conclusion specifically lists the criteria needed in order to accomplish this task. 

Several excellent reviews are available covering different scientific purposes and technological applications of phthalocyanines [46-51]. Here, we focus on synthetic aspects of one particular type of Pc-derivative, namely bis(phthalocyaninato) complexes of trivalent lanthanides, as well as analogous heteroleptic complexes containing porphyrin and porphyrin-like ligands. 

It should be noted that the basic reactions used to prepare phthalocyanine derivatives today are fundamentally those developed by Linstead and coworkers in the 1930s [52-54]. Due to the large number of substituted phthalocyanines described in the literature, space limitations mean that a detailed review of synthetic aspects cannot be provided here. The following discussion is concerned with the synthesis of lanthanide phthalocyanines via (i) template tetramerization of phthalonitrile with lanthanide salts, (ii) direct metalation of the metal-free ligands by the salts or (iii) metal exchange of a labile metal ion or ions for a lanthanide. 

Synthetic aspects for access to monovalent fullerene-carbohydrate hybrids were highlighted, but only a few biological applications were mentioned. In contrast, multivalent presentation of saccharides by multiple anchorages to the same structure, or their presentation as antennary glycodendrons, has generated promising results. 

The photocycloaddition of an aldehyde or ketone with an olefin to yield an oxetane was reported by Paterno and Chieffi in 1909. 58> Contemporary studies on the synthetic utility and mechanistic features were initiated nearly 50 years later by Biichi et al. 59) Two review articles summarizing synthetic aspects of Paterno-Biichi reactions have been published 6.12)) and mechanistic studies have been reviewed several times. 6,38,60-62) The reaction involves the addition to olefin of a photo-excited carbonyl moiety. This circumstance makes it advantageous to review this reaction before a discussion of olefin-olefin additions, because the solution photochemistry of carbonyl compounds is probably better understood than any other aspect of organic photochemistry. Many of the reactions of carbonyl compounds have been elucidated during studies of the important phenomena of energy transfer and photosensitization. 63-65)... 

The organometallic chemistry of vanadium has been surveyed in COMC (1982) and COMC (1995).152 153 The chemical and biological importance of vanadium was reviewed in a dedicated edition of Coordination Chemistry Reviews.1 4 Relevant synthetic aspects of vanadium chemistry have also been reviewed,155-158 including early report by Hirao et al. on formation of ketones from organovanadium compounds and acid chlorides.159... 

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