Selective synthesis substitution

Halogen-substituted succinimides are a class of products with important appHcations. /V-Bromosuccinimide [128-08-5] mp 176—177°C, is the most important product ia this group, and is prepared by addition of bromine to a cold aqueous solution of succinimide (110,111) or by reaction of succinimide with NaBr02 iu the presence of HBr (112). It is used as a bromination and oxidation agent ia the synthesis of cortisone and other hormones. By its use it is possible to obtain selective bromine substitution at methylene groups adjacent to double bonds without addition reactions to the double bond (113). 

To date (ca 1996) many potentially usefiil sucrose derivatives have been synthesized. However, the economics and complexities of sucrochemical syntheses and the avadabiLity of cheaper substitutes have limited their acceptance hence, only a few of them are in commercial use. A change in the price and availability of petroleum feedstocks could reverse this trend. Additional impetus may come from regioselective, site-specific modifications of sucrose to produce derivatives to facilitate and improve the economics of sucrochemical syntheses. For example, the microbe yigwbacterium tumifaciens selectively oxidizes sucrose to a three-keto derivative, a precursor of alkylated sucroses for detergent use (50). Similarly, enzymes have been used for selective synthesis of specific sucrose derivatives (21). 

A new, versatile and selective synthesis of 6- and 7-substituted pteridines was reported by Rosowsky (73JOC2073). /3-Keto sulfoxides, which can be viewed as latent a keto aldehydes, react with (251) to give 6-substituted pterins, and the use of a-keto aldehyde hemithioacetals leads in a regiospecific synthesis to the isomeric 7-substituted pterins (equation 85). 

Recent advances in selective synthesis of 6- and 7-substituted pteridines 98H(48)1255. 

Two transformations should be discussed in more detail (1) presence of the amino group in 275 was utilized for the synthesis of the fused isoquinolinium salt 276 bearing the bicyclic heterocycle as an A-substituent <2003JHC1041> (2) selective nucleophilic substitution of 277 with pyrrolidine was reported <2001ZOR604> to yield only substitution on the phenyl substituent without formation of an amide from the ester group 278. 

Panacene (61) is a metabolite of the sea hare Aplysia brasiliana and acts as a fish antifeedent [61]. The synthesis of the racemic natural product, published by Feldman et al. [77] in 1982, takes advantage of the anti-selective SN2 -substitution of the propargylic mesylate 67 with LiCuBr2 (Scheme 18.21). In contrast, the later attempted biomimetic synthesis by treatment of the enyne 68 with NBS or 2,4,4,6-tetrabromocyclohexadienone did not proceed stereoselectively and led to a 1 1 mixture of the target molecule 61 together with its allenic epimer [78]. 

The bromoallene (-)-kumausallene (62) was isolated in 1983 from the red alga Laurencia nipponica Yamada [64a], The synthesis of the racemic natural product by Overman and co-workers once again employed the SN2 -substitution of a propargyl mesylate with lithium dibromocuprate (Scheme 18.22) [79]. Thus, starting from the unsymmetrically substituted 2,6-dioxabicyclo[3.3.0]octane derivative 69, the first side chain was introduced by Swern oxidation and subsequent Sakurai reaction with the allylsilane 70. The resulting alcohol 71 was protected and the second side chain was attached via diastereoselective addition of a titanium acetylide. The synthesis was concluded by the introduction of two bromine atoms anti-selective S -substitution of the bulky propargyl mesylate 72 was followed by Appel bromination (tetrabromo-methane-triphenylphosphine) of the alcohol derived from deprotection of the bromoallene 73. 

In their total synthesis of isolaurallene (66), Crimmins and co-workers [85] relied on the anti-selective S -substitution of a propargylic sulfonate with LiCuBr2 (cf. Schemes 18.21 and 18.22) instead of the enyne cyclization sequence, which had turned out to be unsatisfactory in terms of stereocontrol (Scheme 18.26). 

The reaction of the complex salt 6a with the arylamine 12 affords by regio-selective electrophilic substitution the iron complex 13 [88] (Scheme 11). The oxidative cyclization of complex 13 with very active manganese dioxide provides directly mukonine 14, which by ester cleavage was converted to mukoeic acid 15 [89]. Further applications of the iron-mediated construction of the carbazole framework to the synthesis of 1-oxygenated carbazole alkaloids include murrayanine, koenoline, and murrayafoline A [89]. 

This reaction can furthermore be applied on chiral aminals, affording a straightforward route to optically pure frawi-2,5-pyrrolidines or chiral alkyl-substituted 1,3-oxazoUdines. This method was used for the en an tio selective synthesis of substituted piperidines . 

Figure 6. Variation of the substitution pattern of the reactants (3, 13, 8, and 5) allows the selective synthesis of the isomeric [2]catenanes 14-16.

Bis-substitution of stilbene produces stronger fluorescence and the bis-triazine derivatives of diaminostilbenes have proved to be the most successful brighteners for cellulosics, in particular, and polyamides (60MI11200). The variety of substitution permutations in (90) is almost endless and many primary and secondary homocyclic and heterocyclic amines, thiols and phenols have been used. Synthesis of such compounds is straightforward and utilizes the convenient selectivity to substitution of cyanuric chloride. 4,4 -Diaminostilbene-2,2 -disulfonic acid condenses readily at 0-5 °C with cyanuric chloride, under slightly acidic conditions. In this case cyanuric chloride behaves as a monofunctional acid chloride and, although some by-products are unavoidable, two molecules of cyanuric chloride condense... 

The selective synthesis of substituted 1,2,4-trioxolanes has drawn considerable interest following indications that this heterocycle confers potent pharmacologic activity such as in the antimalarial area. 

A similar method was developed for the synthesis of di- and trisubstituted tetrazolium salts through the quaterni-zation of 1- and 2-monosubstituted tetrazoles, including functionally substituted compounds, with diacetone alcohol <1999CHE1078> and tert-butanol <2001CHE949> in perchloric acid, and 2,5-dimethyl-2,5-hexandiol in sulfuric and perchloric acids <2000CHE326>. In the latter study <2000CHE326>, this method was used for a selective synthesis of binuclear N-substituted tetrazoles and tetrazolium salts. 

However, despite these remarkable properties, zeolites and related materials cannot be considered (as it is sometimes the case) as magic catalysts for the selective synthesis of Fine and Intermediate Chemicals. This is furthermore confirmed by the relatively small number of zeolite catalysed commercial processes, which were developed to substitute the very polluting catalytic systems (e.g. A1C13) currently used in the synthesis of Fine Chemicals. This can be related to several reasons4101... 

The unsubstituted PhOions afford the ortho- ( 40%) and para- ( 20%) arylation products. By contrast, the selective synthesis of either the ortho or the para isomer can be performed when the t-Bu groups substitute two of the three possible coupling positions [20]. In the case of the 2,6-disubstituted phenoxide ion, the para-substituted compound is obtained (Scheme 10.22), and the t-Bu substituents can be easily removed later [20]. 

The 2,6- and 2,4-di-t-butyl phenoxide ions were shown to be more reactive than PhO ions. The reaction of these nucleophiles, mainly of 2,6-di-/-butylphenoxide ion (185), was studied with a considerable variety of compounds in order to achieve the synthesis of biaryls of importance in non-linear optics249,250. In these nucleophiles, the r-butyl groups substitute two of the possible coupling positions in order to perform a selective synthesis of either the o- or the /7-isomer. The substituents can be easily removed later251,252. 

On the other hand, stabilized ylides react with aldehydes almost exclusively via trans-oxaphosphetanes. Initially, a small portion of the cw-isomer may still be produced. However, all the heterocyclic material isomerizes very rapidly to the fnms-configured, four-membered ring through an especially pronounced stereochemical drift. Only after this point does the [2+2]-cycloreversion start. It leads to triphenylphosphine oxide and an acceptor-substituted fnms-configured olefin. This frara-selectivity can be used, for example, in the C2 extension of aldehydes to /ran.v-con figured aj8-unsaturated esters (Figure 9.11) or in the fnms-selective synthesis of polyenes such as /1-carotene (Figure 9.12). 

In Chapter 43 we also gave the structure of timolol, a thia diazole-based [3-blocker drug for reduction of high blood pressure. This compound has an aromatic 1,2,5-thiadiazole ring system and a saturated morpholine as well as an aliphatic side chain. Its synthesis relies on ring formation by rather a curious method followed by selective nucleophilic substitution, rather in the style of the last synthesis. The aromatic ring is made by the action of S2CI2 on cyanamide . 

Azizian, J., Asadi, A., and Jadidi, K. 2001. One-pot highly diastereo-selective synthesis of new 2-substituted 8-(spiro-3 indolino-2-one)-pyrrolo[3,4-a]-pyrrolizine-l,3-diones mediated by azomethine ylide induced by microwave irradiation. Synthetic Communications, 31 272-33. 

Tu and co-workers [56] have developed a facile and selective synthesis of A-substituted 2-aminopyridines 5 via a microwave-assisted MCR which is controlled by the basicity of the amine and the nature of the solvent. When reacted in a solvent mixture of DMF/HOAc (1 1), the desired aminopyridine 5 was formed next to 2,6-dicyanoanilines in nearly equal amounts. However, when the volume ratio was increased to 1 4, compound 5 was obtained as the main product. The elaborated... 

Credico et al. [13] gave the selective synthesis of 2-substituted-4-carboxy oxazoles (i). They optimized the mild and selective procedure so that the 2-substituted-4-carboxy derivatives can be obtained in multi-gram scale. Ball et al. [14] synthesized the various triazole derivatives (ii), bearing the oxazole ring system via a tandem alkylation/cyclisation reaction, exploiting a facilitating dummy bromine atom. 

Credico BD, Reginato G, Gonsalvi L et al (2011) Selective synthesis of 2-substituted... 

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