Regiospecificity

The insertion of Ct-olefins on the metal-cairbon bond (P/it-R) of the active sites could be either primary (or metal to Cl) or secondary (or metal to C2). 

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Note 1. The lithiation of monoalky1al 1 enes is not completely regiospecific. The ratio of a- to ylithiated allene varies from about 80 20 for methyl-allene to 93 7 for hexylallene. tert.-Butylallene, however, is metallated exclusively on the terminal carbon atom. 

The ij-arylpalladium bonds in these complexes are reactive and undergo insertion and substitution reactions, and the reactions offer useful methods for the regiospecific functionalization of the aromatic rings, although the reac-... 

Imidazole can be A -allylated. The A -glycosylimidazole 299 is prepared by regiospecific amination at the anomeric center with retention of configuration. Phenoxy is a good leaving group in this reaction[181]. Heterocyclic amines such as the purine base 300 are easily allylatedfl 82]. 

The decarboxylation-allylation of allyl enol carbonates proceeds smoothly[450]. The isomeric enol carbonates 699 and 701 of the enone 698 undergo regiospecific allylation, giving the regioisomers 700 and 702 selectively. 

Ailyl enol carbonates derived from ketones and aldehydes undergo Pd-cat-alyzed decarboxylation-elimination, and are used for the preparation of a, /3-unsaturated ketones and aldehydes. The reaction is regiospecific. The regio-isomenc enol carbonates 724 and 726, prepared from 723, are converted into two isomeric enones, 725 and 727. selectively. The saturated aldehyde 728 can be converted into the a,/3-unsaturated aldehyde 730 via the enol carbonate 729[459]. 

Kharasch proposed that hydrogen bromide can add to alkenes by two different mechanisms both of which are regiospecific The first mechanism is electrophilic addi tion and follows Markovmkov s rule... 

The most attractive feature of the Wittig reaction is its regiospecificity The location of the double bond is never m doubt The double bond connects the carbon of the ongi nal C=0 group of the aldehyde or ketone and the negatively charged carbon of the yhde... 

The Wittig reaction (Sections 17 12-17 13) Reaction of a phosphorus ylide with aldehydes and ketones leads to the formation of an alkene A versa tile method for the regiospecific prepa ration of alkenes... 

Similar regiospecific syntheses employing PMBs and diaLkylnaphthalene have been used to prepare 2,6-dimethyl naphthalene [581-42-0] which is oxidized to the corresponding 2,6-naphthalenedicarboxyHc acid [1141-38-4] also used as a monomer for Hquid crystal polymers. 

Good yields of 2,4-diaminoquinolines are obtained through either Lewis acid- or base-induced cyclization of 2-amidinobenzonitriles (20) (58). The method avoids both the harsh conditions and lack of regiospecificity characteristic of earlier preparations. 

The Lewis acid-catalyzed cyclization of 3-anaino-2-alkerLirnines (21) leads to a wide variety of alkyl- and aryl-substituted quinolines (59). The high regiospecificity and the excellent yields obtained make this process promising. 

In the foUowiag cases, only those reactions ia which there is no chain growth, or at most dimerisation, are considered (see Olefin polymers). Alkyl titanium haUdes can be prepared from alkyl aluminum derivatives. The ring stmcture imparts regiospecificity to the ensuing carbometalation (216) ... 

Ester, ether, and cycHc acetal groups are used as blocking groups to allow regiospecific reactions to take place, ie, reaction at specific unblocked hydroxyl groups. 

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). 

A kind of modification of the Polonovski-Boon synthesis is the reaction of 5,6-dihalopyrimidines with ethylenediamine derivatives. Depending on the bulkiness of the amino substituents a more or less regiospecific condensation may proceed (71CB780), as shown recently in the reaction of 5-bromo-6-chloro-l,3-dimethyluracil (279) with 2-methyl-amino- -propylamine to form l,3,5,6-tetramethyl-5,6,7,8-tetrahydrolumazine (280 equation 99) (80Ba3385). 

Treatment of pyrrole, 1-methyl-, 1-benzyl- and 1-phenyl-pyrrole with one mole of A -bromosuccinimide in THF results in the regiospecific formation of 2-bromopyrroles. Chlorination with IV-chlorosuccinimide is less selective (8UOC2221). Bromination of pyrrole with bromine in acetic acid gives 2,3,4,5-tetrabromopyrrole and iodination with iodine in aqueous potassium iodide yields the corresponding tetraiodo compound. 

Directive effects on lithiation have also been studied. The regiospecific /3-metallation of A-methylpyrrole derivatives and 2-substituted furans has been effected by employing the directive effect of the oxazolino group (82JCs(Pl)1343). 2-Substituted furans and thiophenes are metallated in the 5-position. The formation of 2-lithio-3-bromofuran on treatment of... 

A-Substituted pyrroles, furans and dialkylthiophenes undergo photosensitized [2 + 2] cycloaddition reactions with carbonyl compounds to give oxetanes. This is illustrated by the addition of furan and benzophenone to give the oxetane (138). The photochemical reaction of pyrroles with aliphatic aldehydes and ketones results in the regiospecific formation of 3-(l-hydroxyalkyl)pyrroles (e.g. 139). The intermediate oxetane undergoes rearrangement under the reaction conditions (79JOC2949). 

Since /V-acylation is a reversible process, it has allowed the regiospecific alkylation of, for example, imidazoles to give the sterically less favored derivative. This principle is illustrated in Scheme 7 (80AHC(27)24l). 

Scheme 4 shows in a general manner cyclocondensations considered to involve reaction mechanisms in which nucleophilic heteroatoms condense with electrophilic carbonyl groups in a 1,3-relationship to each other. The standard method of preparation of pyrazoles involves such condensations (see Chapter 4.04). With hydrazine itself the question of regiospecificity in the condensation does not occur. However, with a monosubstituted hydrazine such as methylhydrazine and 4,4-dimethoxybutan-2-one (105) two products were obtained the 1,3-dimethylpyrazole (106) and the 1,5-dimethylpyrazole (107). Although Scheme 4 represents this type of reaction as a relatively straightforward process, it is considerably more complex and an appreciable effort has been expended on its study (77BSF1163). Details of these reactions and the possible variations of the procedure may be found in Chapter 4.04. 

A similar regiospecific [2 -I- 2] cycloaddition across a C=S group occurred when benzoyl isothiocyanate (436) and 2,3-diphenyl-1-azirine were heated in refiuxing benzene for 12 hours. The product obtained was shown to be (438) and an intermediate such as (437) could also be involved in this cycloaddition (74JOC3763). In contrast, thiobenzoyl isocyanate added in a [4-1-2] fashion, and after ring expansion gave a thiadiazepine derivative. 

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