Thiophenes ipso substitution

Interesting results have been obtained in intramolecular acylation reactions involving pyrrole and thiophene derivatives. A muscone synthesis involves selective intramolecular acylation at a vacant a-position (Scheme 18) (80JOC1906). In attempts to prepare 5,5-fused systems via intramolecular acylation reactions on to a jS-position of a thiophene or a pyrrole, in some cases ipso substitution occurs with the result that rearranged products are formed (Scheme 19) (82TH30200). 

The synthesis and chemistry of iodonium thiophene derivatives have been studied <00AM133, 00TL5393>, for example, the preparation of 46 involved the ipso substitution of 2-stannylthiophene 45 <00CC649>. A similar ipso substitution of 2-stannylbenzo[b]thiophene 47 with tetranitromethane gave 2-nitrobenzo[ >]thiophene (48) . 

It is obvious from the examples of ipso substitution discussed above that the elimination of N02 from the ipso intermediate is greatly favoured [k2 k ), leading irreversibly to the substitution products. This is because -N02 is a stable radical. On the other hand, if in the ipso intermediate (229) both R and X form strong bonds to the carbon atom, then the intermediate may be forced to decay by other processes, i.e. neither revert to (228) nor undergo substitution to (230). An example is provided by the reaction of the dialdehyde (239) with the adamantyl radical (Scheme 65) (80ACR51, 80JCS(P2)1336). The two major products are 2-adamantylthiophene-5-carbaldehyde (241 19%) and 2-adamantyI-thiophene-3,5-dicarbaldehyde (244 56%). The formation of both can be explained from the common ipso intermediate (240). The loss of the formyl group from this to form (241)... 

A variety of reaction conditions have failed to produce the 3-bromo derivative from (130), perhaps because ring strain promotes ipso-substitution and macroring opening, whereas (135 = 11) is brominated (25-30%) with NBS in acetic acid to give (136) (76ACS(B)34l). Ethyllithium reacts with (136) to open the thiophene ring and give (137). 

The acid-catalyzed rearrangements of substituted pyrroles and thiophenes consequent on ipso protonation have been referred to previously (Section 3.02.2.4.2). There is some evidence that these rearrangements are intramolecular in nature since in the case of acid-induced rearrangement of 2-acylpyrroles to 3-acylpyrroles no intermolecular acylation of suitable substrates could be demonstrated (Scheme 10) (8UOC839). 

The NMR chemical shifts of some substituted thiophenes are listed in Table 37. Highly electronegative substituents cause the largest downfield shift on the ipso-csahon atom but the adjacent carbons are upfield as compared to thiophene. For substituents at the 2-position, the C-4 carbon resonances are the least affected, while for 3-substituted thiophenes, the C-5 resonances do not change much. 

Another germanium-based hnker has been developed for solid-phase synthesis of a pyrazole hbrary [79]. A new iterative synthesis of regioregular oligothiophenes has been developed in which double-couphng after each iteration minimizes deletion sequences. The method exploits the susceptibility of a-silyl- but not a-ger-myl-substituted thiophene derivatives towards nucleophilic ipso protodemetalation and features an unusual base-free Suzuki-type coupling product. The strategy... 

Tin Reagents. ipso-Monoiodination of 3,4-bis(trimethylsilyl)thiophene followed by Pd-catalyzed cross-coupling with stannylated acetylene gives the monalkyne 64. Distanny-lated acetylene will give the alkyne substituted at both termini 65 (Scheme 30). 

Substitution reactions of thiophen derivatives have received attention recently, particularly of nitro-thiophens, in which both ipso- and cme-substitutions may occur or in which radical chain reactions may be involved. Isomeric bromo-... 

The examples of nucleophilic substitution discussed in Sect. 3.4 belong to the ipso-type [185]. In c/ne-substitution, the leaving group departs from the position adjacent to the nucleophile addition site, and in teZe-substitution, the leaving group departs from a more remote position on the ring or even from a side-chain [159]. cine- and feZe-substitutions of various nonaromatic, aromatic and heteroaromatic compounds, including thiophene, have been reviewed [185]. 

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