Synthetic procedures

Chapter I first describes some common synthons and corresponding reagents. Emphasis is on regioselective carbanion formation. In the second part some typical synthetic procedures in the following order of "arrangements of functionality in the target molecule" are given ... 

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

These compounds can be made from the starting materials listed in this chapter in a fev steps. Try to find out starting materials and propose synthetic procedures of your own Then compare with the procedures given in the journal. If you regularly make up your own problems from scientific journals, work them through seriously, and slowly get to more complicated target molecules, you cannot fail to learn a lot about solving synthetic problems in a realistic manner ... 

As for the other volumes in this series, examples of synthetic procedures have been given. These have been chosen to indicate the basic operations involved... 

Synthetic procedures involving other types of intermediates can be based on 2-lithiation. An indirect 2-alkylation can be carried out via indol-2-ylborates which can be prepared by addition of 2-lithioindoles to trialkylboranes. 

The chemistry of heterocyclic compounds is one of the most complex branches of organic chemistry. It is equally interesting for its theoretical implications, for the diversity of its synthetic procedures, and for the physiological and industrial significance of heterocyclic compounds. 

You learned in Section 17 8 of the relationship among hemiacetals ketones and alcohols the for mation of phenol and acetone is simply an example of hemiacetal hydrolysis The formation of the hemiacetal intermediate is a key step in the synthetic procedure it is the step in which the aryl—oxygen bond is generated Can you suggest a reasonable mechanism for this step" ... 

Only a few of the wide variety of synthetic procedures which yield aldehydes as products are used for large-scale commercial preparation. A more complete discussion of syntheses can be found ia the Hterature (10,11). 

Methacryhc acid and its ester derivatives are Ctfjy -unsaturated carbonyl compounds and exhibit the reactivity typical of this class of compounds, ie, Michael and Michael-type conjugate addition reactions and a variety of cycloaddition and related reactions. Although less reactive than the corresponding acrylates as the result of the electron-donating effect and the steric hindrance of the a-methyl group, methacrylates readily undergo a wide variety of reactions and are valuable intermediates in many synthetic procedures. 

Mechanistic studies on the formation of PPS from polymerization of copper(I) 4-bromobenzenethiolate in quinoline under inert atmosphere at 200°C have been pubUshed (91). PPS synthesized by this synthetic procedure is characterized by high molar mass at low conversions and esr signals consistent with a single-electron-transfer mechanism, the Sj l-type mechanism described earlier (22). 

The small synthetic scale used for production of many labeled compounds creates special challenges for product purification. Eirst, because of the need for use of micro or semimicro synthetic procedures, the yield of many labeled products such as high specific activity tritiated compounds is often low. In addition, under such conditions, side reactions can generate the buildup of impurities, many of which have chemical and physical properties similar to the product of interest. Also, losses are often encountered in simply handling the small amounts of materials in a synthetic mixture. As a consequence of these considerations, along with the variety of tracer chemicals of interest, numerous separation techniques are used in purifying labeled compounds. 

Generally, labeled compounds are prepared by procedures which introduce the radionuchde at a late stage of the synthesis. This allows for maximum radiochemical yields, and reduces the handling time of radioactive material. When dealing with short half-life isotopes, a primary consideration is the time required to conduct synthetic procedures and purification methods. 

Synthetic Heme. Synthetic compounds that biad or chelate O2 have been produced. These compounds are commercially attractive because manufacture and Hcensure might be developed as a dmg, rather than as a biological product. It has been shown that synthetic hemes can be used to transfuse animals (53). Although synthetic O2 carriers would avoid the limited hemoglobin supply problem, the synthetic procedures are very tedious, and the possibihty of scale up seems remote. 

Syntheses, crystallization, structural identification, and chemical characterization of high nuclearity clusters can be exceedingly difficult. Usually, several different clusters are formed in any given synthetic procedure, and each compound must be extracted and identified. The problem may be compounded by the instabiUty of a particular molecule. In 1962 the stmcture of the first high nuclearity carbide complex formulated as Fe (CO) C [11087-47-1] was characterized (40,41) see stmcture (12). This complex was originally prepared in an extremely low yield of 0.5%. This molecule was the first carbide complex isolated and became the foremnner of a whole family of carbide complexes of square pyramidal stmcture and a total of 74-valence electrons (see also Carbides, survey). 

Synthetic procedures are available for the preparation of fluoro, chloro, bromo and iodo compounds from the corresponding lithio derivatives. Perchloryl fluoride (FCIO3), N-chlorosuccinimide, bromine and iodine are examples of reagents which can be used to introduce fluorine, chlorine, bromine and iodine, respectively. 

The synthesis of these five-membered ring systems has classically been discussed in terms of the ring system formed. In recent years many synthetic procedures have been classified in terms of the bonds being formed and the position and nature of the heteroatoms involved. Both methods have their advantages, and also their drawbacks. 

The synthetic procedure described is based on that reported earlier for the synthesis on a smaller scale of anthracene, benz[a]anthracene, chrysene, dibenz[a,c]anthracene, and phenanthrene in excellent yields from the corresponding quinones. Although reduction of quinones with HI and phosphorus was described in the older literature, relatively drastic conditions were employed and mixtures of polyhydrogenated derivatives were the principal products. The relatively milder experimental procedure employed herein appears generally applicable to the reduction of both ortho- and para-quinones directly to the fully aromatic polycyclic arenes. The method is apparently inapplicable to quinones having an olefinic bond, such as o-naphthoquinone, since an analogous reaction of the latter provides a product of undetermined structure (unpublished result). As shown previously, phenols and hydro-quinones, implicated as intermediates in the reduction of quinones by HI, can also be smoothly deoxygenated to fully aromatic polycyclic arenes under conditions similar to those described herein. 

Montgomery et al. in Synthetic Procedures in Nucleic Acid Chemistry (Zorbach and Tipson eds) Wiley ... 

Both common and systematic names of compounds are used throughout this volume, depending on which the Editor-in-Chief feels is most appropriate. Preparations appear in the alphabetical order of names of the compound or names of the synthetic procedures. The Chemical Abstracts indexing name for each title compound, if it differs from the title name, is given as a subtitle. Because of the major shift to new systematic nomenclature adopted by Chemical Abstracts in 1972, many common names used in the text are immediately followed by the bracketed, new names. Whenever two names are concurrently in use, the carre CChemical Abstracts name is adopted. The prefix n- is deleted from -alkanes and w-alkyls. All reported dimensions are now expressed in S st me International units. 

A very convenient synthetic procedure for nitration involves the mixing of a nitrate salt with trifluoroacetic anhydride. This presumably generates trifluoroacetyl nitrate. 

Finally, Vogtle and his coworkers have prepared a number of cascade molecules which are structurally related to the aforementioned systems. These are repeating ring units of increasingly large cavity size and are prepared by repetitive synthetic procedures. Typically, an amine is cyanoethylated, the nitrile reduced to an amine which may then be further cyanoethylated and reduced or cyclized with a diacid halide. The rather elaborate scheme is illustrated in ref. 61 and examples of the structural type are shown in Table 8.4. 

Modem Synthetic Procedures for the Ruonnation of Organic Molecules Haas, A, Lieb, M Chimia 39, 134-140 128... 

The synthetic procedure has been extended to the preparation of trifluoro-acetyl hypofluorite [16, 17], long-chain perfluorinated hypofluorites [18, 19], and radiolabeled hypofluorites [II, 12],... 

The addition of halogenated aliphatics to carbon-carbon double bonds is the most useful type of carbon-carbon bond forming synthetic method for highly halogenated substrates Numerous synthetic procedures have been developed for these types of reactions, particularly for the addition of perfluoroalkyl iodides to alkenes using thermal or photolytic initiators of free radical reactions such as organic peroxides and azo compounds [/]... 

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