From ferrocene to decasubstituted enantiopure ferrocene-1,1'-disulfoxide derivatives.

The functionalization of (,)-,'-di--butylferrocene-1,1'-disulfoxide by deprotolithiation-electrophilic trapping sequences was studied towards polysubstituted, enantiopure derivatives for which the properties were determined. While the 2,2'-disubstituted ferrocene derivatives were obtained as expected, subsequent functionalization of the 2,2'-di(phenylthio) and 2,2'-bis(trimethylsilyl) derivatives occurred primarily at the 4- or 4,4'-positions. This unusual regioselectivity was discussed in detail in light of p values and structural data.

Synthesis of Polysubstituted Ferrocenesulfoxides.

The purpose of the study is to design synthetic methodologies, especially directed deprotometalation using polar organometallic reagents, to access polysubstituted ferrocenesulfoxides. From enantiopure 2-substituted (SiMe, PPh) --butylferrocenesulfoxides, a third substituent was first introduced at the 5 position (SiMe, I, D, C(OH)Ph, Me, PPh, CHNMe, F) and removal of the trimethylsilyl group then afforded 2-substituted ferrocenesulfoxides unreachable otherwise. Attempts to apply the "halogen dance" reaction to the ferrocenesulfoxide series led to unexpected results although rationalized in light of calculated p values.

Deprotometalation-Iodolysis and Direct Iodination of 1-Arylated 7-Azaindoles: Reactivity Studies and Molecule Properties.

Five protocols were first compared for the copper-catalyzed C-N bond formation between 7-azaindole and aryl/heteroaryl iodides/bromides. The 1-arylated 7-azaindoles thus obtained were subjected to deprotometalation-iodolysis sequences using lithium 2,2,6,6-tetramethylpiperidide as the base and the corresponding zinc diamide as an in situ trap. The reactivity of the substrate was discussed in light of the calculated atomic charges and the p values.

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium-zinc base and regioselectivity-computed CH acidity relationship.

The synthesis of N-arylated pyrroles and indoles is documented, as well as their functionalization by deprotonative metallation using the base in situ prepared from LiTMP and ZnCl2·TMEDA (1/3 equiv). With N-phenylpyrrole and -indole, the reactions were carried out in hexane containing TMEDA which regioselectively afforded the 2-iodo derivatives after subsequent iodolysis. With pyrroles and indoles bearing N-substituents such as 2-thienyl, 3-pyridyl, 4-methoxyphenyl and 4-bromophenyl, the reactions all took place on the substituent, at the position either adjacent to the heteroatom (S, N) or ortho to the heteroatom-containing substituent (OMe, Br).

Deprotometalation-iodolysis and computed CH acidity of 1,2,3- and 1,2,4-triazoles. Application to the synthesis of resveratrol analogues.

1-Aryl- and 2-aryl-1,2,3-triazoles were synthesized by N-arylation of the corresponding azoles using aryl iodides. The deprotometalations of 1-phenyl-1,2,3-triazole and -1,2,4-triazole were performed using a 2,2,6,6-tetramethylpiperidino-based mixed lithium-zinc combination and occurred at the most acidic site, affording by iodolysis the 5-substituted derivatives. Dideprotonation was noted from 1-(2-thienyl)-1,2,4-triazole by increasing the amount of base.

Deproto-metallation using a mixed lithium-zinc base and computed CH acidity of 1-aryl 1H-benzotriazoles and 1-aryl 1H-indazoles.

1-Aryl-1H-benzotriazoles and -1H-indazoles were synthesized, and their deproto-metallation using the base prepared by mixing LiTMP with ZnCl2·TMEDA (1/3 equiv.) was studied. In the indazole series, reactions occurring at the 3 position were followed by ring opening, and functionalization of the substrate was only found possible (on the sulfur ring) using 2-thienyl as aryl group.

Computed CH acidity of biaryl compounds and their deprotonative metalation by using a mixed lithium/zinc-TMP base.

With the aim of synthesizing biaryl compounds, several aromatic iodides were prepared by the deprotonative metalation of methoxybenzenes, 3-substituted naphthalenes, isoquinoline, and methoxypyridines by using a mixed lithium/zinc-TMP (TMP=2,2,6,6-tetramethylpiperidino) base and subsequent iodolysis. The halides thus obtained, as well as commercial compounds, were cross-coupled under palladium catalysis (e.g.

Deproto-metallation and computed CH acidity of 2-aryl-1,2,3-triazoles.

2-Aryl-1,2,3-triazoles were synthesized by cyclization of the corresponding glyoxal arylosazones, generated from commercial arylhydrazines. The deproto-metallation of 2-phenyl-1,2,3-triazole was attempted using different 2,2,6,6-tetramethylpiperidino-based mixed lithium-metal (Zn, Cd, Cu, Co, Fe) combinations, giving results in the case of Zn, Cd, and Cu. The lithium-zinc combination was next selected to apply the deprotonation-iodination sequence to all the 2-aryl-1,2,3-triazoles synthesized.

Deprotonative metalation of chloro- and bromopyridines using amido-based bimetallic species and regioselectivity-computed CH acidity relationships.

A series of chloro- and bromopyridines have been deprotometalated by using a range of 2,2,6,6-tetramethylpiperidino-based mixed lithium-metal combinations. Whereas lithium-zinc and lithium-cadmium bases afforded different mono- and diiodides after subsequent interception with iodine, complete regioselectivities were observed with the corresponding lithium-copper combination, as demonstrated by subsequent trapping with benzoyl chlorides. The obtained selectivities have been discussed in light of the CH acidities of the substrates, determined both in the gas phase and as a solution in THF by using the DFT B3LYP method.

N-aryl pyrazoles: DFT calculations of CH acidity and deprotonative metallation using a combination of lithium and zinc amides.

A series of N-aryl and N-heteroaryl pyrazoles have been deproto-metallated using a 2,2,6,6-tetramethylpiperidino-based mixed lithium-zinc combination. Mono-, di-, and tri-iodides have been obtained after subsequent trapping with iodine, depending on the substrate and on the quantity of base used. The results have been discussed in the light of the CH acidities of the substrates, determined both in the gas phase and in THF solution using the DFT B3LYP method.