Versatile synthon

Scheme 6 shows representative members of these three groups. Other combinations are possible and the design of an appropriate bielectrophile for use as a versatile synthon presents a considerable synthetic challenge, as by virtue of the structural entities involved they are extremely reactive. 

Dioxathiolane oxides as epoxide equivalents and versatile synthons 98AHC(68)89. 

Arylthallium bis(trifluoroacetate)s (10.70) are versatile synthons for various reactions, e.g., acylations (Larock and Fellows, 1982) and photolytic cyanations (Taylor et al., 1970), as shown in Scheme 10-93. Copper-catalyzed cyanations (Uemura et al., 1972) can be carried out at 115 °C with arylthallium (acetate)(perchlorate) (Scheme 10-94). 

Alternative conditions for reductive decyanations can be used. The allylic ether in compound 26, an intermediate in a total synthesis of (-)-roxaticin, was prone to reduction when treated with lithium in liquid ammonia. Addition of the substrate to an excess of lithium di-ferf-butylbiphenylide in THF at -78°C, and protonation of the alkyllithium intermediate provided the reduced product 27 in 63% yield, as a single diastereomer (Eq. 7). a-Alkoxylithium intermediates generated in this manner are configurationally stable at low temperature, and can serve as versatile synthons for carbon-carbon bond forming processes (see Sect. 4). 

Manhas, M. S., Wagle, D. R., Chiang, J., and Bose, A. K. (1988). Conversion ofb-lactams to versatile synthons via molecular rearrangement and lactam cleavage. Heterocydes 21, 1755-1802. 

N-Boc-2-Bromoglycine tert-butyl ester (1), introduced Steglich and coworkers, is a versatile synthon for electrophilic glycine,5 an tnpcDortant tool in the synthesis of non-proteinogenic amino acids. 

Backvall and Juntunen and Fuchs and Braish have developed ( )-2-phenylsuphonyl-1,3-dienes prepared under Julia conditions as versatile synthones for a variety of organic transformations103. These dienes undergo facile Diels-Alder reaction and subsequent 1,4-elimination of sulphinic acid by base to generate a new diene (equation 62)103a. An elegant extension of this method is to use chiral sulfinylmaleate which, on Diels-Alder... 

The hydrolysis of racemic non-natural amides has led to useful products and intermediates for the fine chemical industry. Thus hydrolysis of the racemic amide (2) with an acylase in Rhodococcus erythrolpolis furnished the (S)-acid (the anti-inflammatory agent Naproxen) in 42 % yield and > 99 % enantiomeric excess1201. Obtaining the 7-lactam (—)-(3) has been the subject of much research and development effort, since the compound is a very versatile synthon for the production of carbocyclic nucleosides. An acylase from Comamonas acidovor-ans has been isolated, cloned and overexpressed. The acylase tolerates a 500 g/ litre input of racemic lactam, hydrolyses only the (+)-enantiomer leaving the desired intermediate essentially optically pure (E > 400)[211. 

Mercaptoacetic acid could be used as a versatile synthon for the synthesis of 17/,3//-thiazolo[3,4-tf]benzimidazole-type compounds <1996FA279, 1997FA673>. For instance, 2,3-diaminopyridine and 2-mercaptoacetic acid were reacted in a three-component reaction with a suitable carbonyl compound and provided the 17/,3//-thiazolo[3,4- ]-imidazo[4,5- ]pyridines 451 (Equation 212) <1994FA345>. 

Allenes as versatile synthons including Diels-Alder reactions and especially intramolecular cycloadditions of this type were reviewed by Aso and Kanematsu [338], In some cases of intramolecular Diels-Alder reactions of open-chain starting materials such as 340 [339], 342 [339] and similar acceptor-substituted allenes [156], the formation of two new six-membered rings seems to be favorable if possible (Scheme 7.48). The non-activated cumulated C=C bond of 340 takes part in the [4+ 2]-cycloaddition and hence the necessary reaction temperature is high. On the other hand, the progressive truncation of the tether and the electron deficiency of the allenic C=C bond involved give rise to a remarkable Diels-Alder reactivity of the sulfone 346 generated in situ from sulfoxide 345 [339]. 

Nitroalkenes are excellent Michael acceptors, and asymmetric 1,4-additions to nitroalkenes (Scheme 7.22) provide access to highly versatile synthons, since the nitro group is readily reduced to the corresponding amine [74]. Seebach, employing a... 

Therefore, the chiral cyanohydrins are valuable and versatile synthons as their single hydroxyl asymmetric centre is accompanied by at least one other chemical functionality. Thus with careful functional group protection, differential and selective chemical transformations can be performed. Such synthetic techniques lead to production of interesting bioactive compounds and natural products. These products include intermediates of j3-blockers 15 1117], j3-hydroxy-a-amino acids 16 [118],chiral crown ethers 17 [lll],coriolic acid 18 [120], sphingosines 19 [121], and bronchodilators such as salbutamol 20 [122] (Fig. 3). 

Poly(phenylchlorosilane) can be considered as a versatile synthon for the preparation of a variety of functionalized polysilanes. Indeed, its reactions with MeOH or MeMgBr afforded polysilane containing Si—OMe or Si—Me moieties, respectively, whereas its reaction with LiAlH4 regenerated the starting poly(phenylhydrosilane) [21,22]. 

Although this review is by no means exhaustive, it should present an impression of the importance of iminophosphoranes as versatile synthons in heterocyclic synthesis. Much attention was paid to the aza-Wittig reaction, which enables the preparation of a wide range of simple and complex heterocyclic systems. 

Although the 3,l-perhydrobenzoxazine-2,4-diones are the saturated analogs of the versatile synthon isatoic anhydride, few articles deal with the synthesis of these derivatives. 

Another versatile synthon for the preparation of fullerene derivatives with polar groups on the side chain is the l,2-(carboxymethano)[60]fullerene 123, which can be obtained either from the corresponding ethoxycarbonylmethyl carboxylate 124 or tert-butyl carboxylate 125, which themselves are accessible by the reaction of the corresponding diazoacetate with Cjq (Scheme 4.26) [113],... 

This procedure is a modification of the previously-published procedure by Boeckman and Thomas. The acetone diketene adduct serves as a versatile, activated g-keto ester equivalent Conversion of this material to the phosphonate by the procedure described above affords an even more versatile synthon which is useful for the preparation of protected analogues of the... 

J. Ermert, C. Hocke, T. Ludwig, R. Gail, H.H. Coenen, Comparison of pathways to the versatile synthon of no-carrier-added 1-bromo-4-[ F]fluorobenzene, J. Label. Compds Radiopharm. 47 (2004) 429-441. 

M. S. Marthas, D.R. Wagle, J. Chiang u. A. K. Bose, Hetcrocycles 27, 1755-1802 (1988) . .Conversion of /J-Lactams to Versatile Synthons via Molecular Rearrangement and Lactam Cleavage". 

Ethenediyl carbonate (l,3-dioxol-2-one vinylene carbonate, 417) is a readily available,270 versatile synthon having pronounced dienophilic properties.270-275 Diels-Alder adducts of 417 with 1,4-di-acetoxy-1,3-butadiene and furan were selectively converted into cy-clitols,256 257-275 and also served as precursors of DL-ribose derivatives258 (see Section IV, 2). Another possibility of applying 417 as an equivalent of a 1,2-dihydroxyethane unit has been demonstrated in a synthesis of racemic apiose. Photochemical cycloaddition of 417 to 1,3-diace-toxy-2-propanone (418) gave the oxetane derivative 419, which, on alkaline hydrolysis, afforded DL-apiose (420) in 23% yield.1... 

Sn2 ring opening by attack of a nucleophile on an ethenyl substituent (e.g. Scheme 60) has assumed importance in natural products synthesis (80JCS(P1)2084, cf. 81JA5969). The cyclopentene oxide (63) is a versatile synthon for alkylated, functionalized cyclopentanes (Scheme 61) (81JA2112). 

The a-methoxylated derivatives are shown to be versatile synthons because of the reactivity of the methoxy group near the nitrogen atom, a-Methoxycarbamates, prepared by anodic oxidation, were used as key intermediates in the synthesis of a-amino acids,200 a new carbon-phosphorus bond-forming reaction,200 and in a new method of acylation of aliphatic amines at the -position.201 The application of this reaction to the synthesis of pyrrolidine, piperidine, and tropane alkaloids is also described.202... 

K. Kakinuma, Y. Iihama, I. Takagi, K. Ozawa, N. Yamauchi, N. Imamura, Y. Esumi, and M. Uramoto, Diacetone glucose architecture as a chirality template. II. Versatile synthon for the chiral deuterium labelling and synthesis of all diastereomers of chirally monodeuterated glycerol, Tetrahedron 48 3163 (1992). 

Most derivatives of this ring system are prepared from 2-aminopyrimidines. Ethoxy-methylenemalonic ester (220) is a versatile synthon which can be reacted with 2-aminopyrimidines to give pyrimido[l,2-a]pyrimidine precursors. Reaction of 2-aminopyrimidine (219) with this ester gives the aminomethylenemalonic ester (221), which can be thermally cyclized to the heterocyclic ester (222). The enamine analogous to (221) which is derived from 2-amino-4,6-dimethylpyrimidine cannot be cyclized under these conditions. Presumably this cyclization fails due to steric hindrance of the methyl groups (72JMC1203). 

Oxazinium and -thiazinium cations are 67r-aromatic systems which readily react with nucleophiles at C-6. Ring opening is normally followed by recyclization so that a variety of heterocyclic systems are then formed. The behaviour of the oxygen and sulfur compounds are almost identical and so, as the latter are usually prepared from the former, it is not surprising that most attention has focussed on the reactions of 1,3-oxazinium species (72S333). These versatile synthons react with ammonia, for example, to give pyrimidines, while hydrazines afford pyrazoles and hydroxylamine produces isoxazoles (Scheme 20). 

J-Ethoxyvinyl Polyfluoroalkyl Ketones-Versatile Synthons in Fluoroorganic Chemistry ... 

Westman, J., Lundin, R., Stalberg, J., Ostbye, M., Franzen, A. andHurynowicz, A., Alkylaminopropenonesand alkylamino-propenoates as efficient and versatile synthons in microwave-assisted combinatorial synthesis, Comb. Chem. High TJtroughput Screen., 2002, 5, 565-570. 

Isatoic anhydride can be used as a versatile synthon for the synthesis of a diverse set of molecules. The isatoic anhydride can be reacted with amines, amides, hydrazides, isothiocyanates, diketo substrates, aminoacids, amino-, thio or hydroxy anilines, as well as in a three-component reaction with aldehydes and amines to form a large set of diverse pharmacophores. 

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