Salvatore Cabiddu

Metalation reactions. XIV. Regiospecific preparation of polysubstituted benzenes via mono- or di-lithiation reactions of aromatic thioethers☆

Abstract The preparation of polyfunctionalized aromatic thioethers either by one-step dilithiation or by two successive one-flask monometalation reactions is described. By acting on 1 two equal or different electrophiles one on the thiomethyl group and one in the ortho -position with respect to it are introduced; by acting on 11 and on 35 the substitution involves the thiomethyl carbon atom and that in the ortho -position with respect to the alkoxy group. In the case of the homologous isopropylthio (23) the substitution involves the two aryl carbon atoms in the ortho -position to both functions. In the case of the p -disubstituted isomers (49, 59) analogous behaviour to ortho isomers in one-step metalation reaction is observed, while the two hydrogen atoms in the ortho -positions to the methoxy group are substituted when two successive monometalations are employed. The metalation of 40 results low selective. The behaviour of 79 and 93 is analogous to 1, while 72, 88 and 96 undergo only one-step monometalation reactions.

Cleavage of ethereal bond : IX. The reducing action of Grignard reagents on 1,3-benzoxathiole and 1,3-benzodioxole derivatives

Abstract Some reactions of 1,3-benzoxathioles and 1,3-benzodioxoles with Grignard reagents were examined in order to verify whether or not reduction products were present in addition to the substitution and elimination products previously observed. The reaction mixtures contain reduction products whenever the Grignard reagent has β-hydrogen atoms, in which case the reagent is likely to act as a hydride transfer agent. The product distribution also depends on steric hindrance by the halogen. 1,3-Benzodioxoles react with isopropylmagnesium bromide to give mixtures of alkanes and alkenes, the former arising from a double hydride ion migration, and the latter from a reduction and elimination process.

Metalation reactions. : IV. Metalation of o-alkyl- and o,o′-dialkyl-substituted alkylthiobenzenes

Abstract Metalation of o -alkyl- and o,o′ -dialkylsubstituted alkylthiobenzenes with n-butyllithium, in the presence and absence of TMEDA, has been investigated. The results showed that metalation at the thioalkyl carbon probably occurs by direct attack of the organolithium reagent, although a transmetalation reaction cannot be excluded in some cases. It has also been found that benzylic, thio-methylic, and ring metalation occurs in ether alone, whereas mainly thio-methylic or ring metalation occurs in the presence of TMEDA.

Metalations of alkoxyalkylthiobenzenes

Abstract Metalation of o-, m- and p-alkoxyalkylthiobenzenes with n-butyllithium is examined. The analysis of the products shows that in the o-compound only a thiomethyl hydrogen is replaced, while in the other compounds studied a ring hydrogen ortho to the alkoxylic group is replaced. The metalation has a low steric requirement.

Metalation reactions: XIII. The reactions of electrophiles with the dilithiated species 1-(α-lithiomethyl)-2-[(α-lithiomethyl)thio]benzene☆

Abstract Direct dimetalation of 1-methyl-2-(methylthio)benzene ( 1 ) gives the dilithiated species ( 2 ) in good yield, which can be used to introduce substituents into the thiomethyl and methyl groups. Species 2 can react also with a variety of dichlorosilanes and dichlorostannanes, and with sulphur chloride, to yield derivatives of 1,3-benzothiasilin, 1,3-benzothiastannin and 1,3-benzodithiin respectively. Reaction of 2 with tetrachlorosilane yields a spirocyclic silicon compound, while reaction with benzoyl chloride yields a derivative of 1-benzothiopyran.

Metallation reactions XXII: Regioselective metallation of (trifluoromethyl)(alkylthio) benzenes

Abstract The metallation reactions of (trifluoromethyl)(alkylthio)benzenes with organolithium reagents and with the butyllithium/potassium tert -butoxide superbasic mixture are here described. The results, according to the theoretical calculations of energy minima, show the monometallation regiochemistry is directed by the sulphur atom. On the other side, the bimetallation, that can be performed only on methylthio derivatives, depends on the organometallic reagent employed. Using butyllithium the stronger coordinative power of sulphur prevails and products metallated in ortho and alpha positions to this atom are mainly formed. With the more basic sec -butyllithium and with the superbase, because of mutual competition between the thioalkyl and trifluoromethyl groups, mixtures of products, coming from metallation in the ortho position to the trifluoromethyl group and in the alpha position of the thiomethylic group, are obtained. In addition, products coming from substitution ortho,alpha to the thiomethyl group are also formed. All mono- and bimetallated intermediates showed to be good synthons for the synthesis of fluoro- and (trifluoromethyl)-substituted benzothiophenes and (trifluoromethyl)benzenes substituted on the thioalkylic chain and/or on the ring.

Metallation reactions. XXI. Metallation of alkyl (alkylthio) benzenes by superbases versus organolithium compounds

Abstract The metallation regiochemistry of alkyl(alkylthio)benzenes with butyllithium or with the superbasic mixture of butyllithium with potassium tert-butoxide is described. The reaction pattern depends on the substrate and the reagent. Butyllithium monometallates the thiomethylic carbon of methyl (methylthio) benzenes and bimetallates the thiomethylic and the annular carbon ortho to the thioethereal group. With superbases the metallation occurs at the thiomethylic and methylic carbon. Metallation with butyllithium of the higher homologs substitutes exclusively the hydrogen ortho to the thioalkylic group, while the superbases attack also the carbon atom alpha to the thioalkyl substituent.

Metallation Reactions. XX. Regioselective Metallation of (Alkylthio)methoxybenzenes by Superbases versus Organolithium Compounds

Abstract (Alkylthio)methoxybenzenes have been metallated using two different metallating agents. The results show that sometimes superbases and butyllithium do not functionalize the same sites. Superbases monometallate the thiomethylic carbon of meta and para (methylthio)methoxybenzenes. The same substrates on the other hand are metallated by butyllithium in ortho to the methoxy group. One-step dimetallation performed with either superbases or butyllithium occurs at the thiomethylic carbon and at the aryl carbon ortho to the methoxy group. Two consecutive one-pot monometallations of the para isomer ( 1c ) with superbases occur at the thiomethylic carbon and at the annular carbon ortho to the methoxy group, in this order. A similar procedure with butyllithium metallates the two ortho positions to the methoxy group. Monometallation of (ethylthio) derivative ( 1d ) yields products substituted in ortho to the methoxy group using either superbases or butyllithium. Dimetallation of this compound always substitutes the hydrogen ortho to the methoxy group and a thiomethylenic hydrogen.

Metallation reactions: XVIII. Regioselective metallation of (alkylthio)benzenes by superbases

Abstract (Alkylthio)benzenes were monometallated at the alpha position by a stoichiometric mixture of butyllithium and potassium t-butoxide and bimetallated at both the alpha and the ortho positions by two equivalents of the same reagent.

Metalation reactions. IX. Dilithiation of aromatic thioethers

Abstract Direct dimetalation of aromatic thioethers gives with good yield the dilithiated species 3 , 4 , 17 , 18 , 25 , 26 . The first four species allowed the simultaneous introduction of an electrophile in the thiomethyl group and in the ring, while the last two species undergo disubstitution in the ring.