From Three Synthons

Of all the possibilities for producing a pyrazine ring from three synthons, only one type of cyclocondensation has emerged from the present survey it involves the reaction of a C—C synthon with two identical N—C synthons, as indicated in the following examples ... 

This discussion is separated into three sections depending on whether fluorine, or polyfluoroalkyl group, is introduced into a heterocycle or whether the heterocycle is formed from fluorinated synthons. Methods of introduction of fluorine into N-containing heterocyclic compounds have been reviewed (90CLY959). 

One learns from these molecular complexes that equivalent synthons can lead to virtually identical crystal structures. Synthons in, V and VI are chemically and geometrically equivalent though they originate from different molecules, a nitrile, an N-oxide and a nitro compound. These three synthons are used in crystal design in almost the same way. So, different molecules may yield similar crystal structures if they are capable of forming equivalent synthons. This is a powerful concept because it establishes a many-to-one correspondence between molecular and crystal structures. 

Three approaches can be used to prepare C-difluoromethyl glycosides hydrogenation of difluorovinylic precursors, difluoromethylation reactions, and synthesis from difluoromethyl synthons. 

Construction of the Cyclopropane Ring from Three-Carbon Synthons. 114... 

The title transformation provides an alternative pathway for the construction of the cyclopropane ring from a synthon of three carbons. The intramolecular cyclization of homoenolate anion equivalents is represented in Scheme 11, Eq. (ii). In practice, several routes involving metals such as Mg, Zn, and Ti, as well as different homoenolate precursors, have been developed [17a-e]. 

We present here an overview of production of these three synthons and their transformations into a wide range of products, from surfactants to multifunctional building-blocks, natural and bioactive products. 

For the synthesis of carotenoids labelled in the central part of the molecule, the C15 + C10 + C15 scheme [62] is used. The preparation of the labelled C 10-central units and the Ci5-end groups as phosphonium salts has been discussed in Sections B.1-B.3. From these synthons, symmetrical carotenoids are synthesized in a one-step procedure, asymmetrical carotenoids in a three-step procedure. By this procedure any carotenoid can be synthesized with C-labels in the central part of the molecule. The procedure is illustrated by the synthesis of the symmetrical carotenoids p,P-carotene (3) and astaxanthin (403) (Scheme 25) and an asymmetrical carotenoid, spheroidene (97) (Scheme 26). 

To summarize, there exist three chemical evolution models that parallel synthetic polymerization procedures and whose reaction conditions may be used as strategies forbiomimetic syntheses of biopolymers from organic synthons ... 

Scheme 3.70 illustrates three examples in which the highly efficient construction of bi- and polycyclic compounds 3-274, 3-276 and 3-278 from 3-273, 3-275 and 3-277, respectively, is depicted. It should be noted that the carbon-silicon bond in the obtained products can be easily cleaved [110] to achieve valuable synthons for further transformations. 

Methyl deoxypodocarpate 127 (Scheme 1) 129) represents a simple problem since the ketone 132 is well-known and readily available from Hagemann s ester in three steps. The problem of geminal alkylation of this ketone stems from its existence as an EjZ mixture of ring fusion isomers. Recognizing that decarbonylation of aldehydes occurs readily with Wilkinson s catalyst creates a structural equivalence of an acetaldehyde chain and a methyl group as in 128. This simple relationship immediately establishes several options, a simple one uses a thioacetal such as 129 as a synthon for the aldehyde. The presence of a carbonyl group three carbons away... 

Heterocycles.—The phosphonium salt (59) is an effective three-carbon synthon, as demonstrated by its reaction with enolates of /9-keto-esters (Scheme 20) to give cyclopentenyl sulphides via an intramolecular Wittig reaction.63 Ylides are also intermediates in the synthesis of dihydrofurans (60) from the cyclopropylphos-phonium salt (61) and sodium carboxylates (Scheme 21).64 Cumulated ylides are very useful for the synthesis of heterocyclic compounds, e.g. (62), from molecules which contain both an acidic Y—H bond and a carbonyl or nitroso-function, as shown in Scheme 22.65... 

Recently, the improved chiral ethyl ketone (5)-141, derived in three steps from (5)-mandelic acid, has been evaluated in the aldol process (115). Representative condensations of the derived (Z)-boron enolates (5)-142 with aldehydes are summarized in Table 34b, It is evident from the data that the nature of the boron ligand L plays a significant role in enolate diastereoface selection in this system. It is also noteworthy that the sense of asymmetric induction noted for the boron enolate (5)-142 is opposite to that observed for the lithium enolate (5)-139a and (5>139b derived from (S)-atrolactic acid (3) and the related lithium enolate 139. A detailed interpretation of these observations in terms of transition state steric effects (cf. Scheme 20) and chelation phenomena appears to be premature at this time. Further applications of (S )- 41 and (/ )-141 as chiral propionate enolate synthons for the aldol process have appeared in a 6-deoxyerythronolide B synthesis recently disclosed by Masamune (115b). 

Since dienolates 1 and 2 represent diacetate synthons, the dienolate derived from 6-ethyl-2,2-dimethyldioxinone can be seen as a propionate-acetate syn-thon. The synthesis of the corresponding dienolate provides a mixture of the E and Z enolates in a 3 5 ratio. The reaction with Ti-BINOL complex 5 generates a 5 1 mixture with the syn isomer as the major diastereomer. After separation of the diastereomers, the enantiomeric excess of the syn isomer was determined to be 100%. The anti isomer was formed in 26% ee. The same transformation performed with boron Lewis acid 7 gave the anti isomer as the major compound, but only with 63% ee. The minor syn isomer was produced with 80% ee. The observed selectivity could be rationalized by an open transition state in which minimization of steric hindrance favors transition state C (Fig. 1). In all three... 

Ketenedithioacetals (1) can formally be considered as S.S-dialkylated dithioacids. However, their reactivity pattern is quite different from that displayed by compounds like dithioacids and dithioesters bearing a thiocarbonyl group, and their syntheses and properties are usually treated apart. The review by Kolb [59] and its 254 references give access to most of the literature in the field (see also [60]). a-Oxoketenedithioacetals (2) are particularly versatile compounds as three-carbon synthons in organic synthesis, and some reviews deal specifically with them [61, 62]. Many efficient procedures are available for their syntheses [59, 61], and number of these make use of the reactions of carbon disulfide with carbanionic species followed by alkylation at the sulfur atoms (see [63] and [64] for the reactions of CS2). 

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