Reductive ring opening of dihydrodibenzothiepine and dihydrodinaphtho-oxepine and -thiepine

Abstract

The 4,4′di- tert-butylbiphenyl (DTBB)-catalysed lithiation of dihydrodibenzothiepine ( 1 ) at −78 °C for 30 min followed by reaction with a carbonyl compound [ t BuCHO, Ph(CH 2) 2CHO, PhCHO, ( n-C 5H 11) 2CO, (CH 2) 5CO, (CH 2) 7CO, (−)-menthone] at the same temperature leads, after hydrolysis with 3 M hydrochloric acid, to sulphanyl alcohols 2 . If after addition of a carbonyl compound as the first electrophile [Me 2CO, (CH 2) 5CO, (−)-menthone], the resulting dianion of type II is allowed to react at room temperature for 30 min, a second lithiation takes place to give an intermediate of type III , which by reaction with a second electrophile [Me 2CO, Et 2CO, (CH 2) 5CO, ClCO 2Et], yields, after hydrolysis, difunctionalised byphenyls 4 . The cyclisation of the sulphanyl alcohol 2c under acidic conditions yields the eight-membered sulphur containing heterocycle 3 . The lithiation of dihydrodinaphthoheteroepines 7 and 10 with 2.2 equiv of lithium naphthalenide in THF at −78 °C followed by reaction with different electrophiles [H 2O, D 2O, t BuCHO, Me 2CO, Et 2CO, (CH 2) 4CO, (CH 2) 5CO] at the same temperature leads, after hydrolysis, to unsymmetrically 2,2′-disubstituted binaphthyls 9 and 12 , respectively. When the lithiation is performed with an excess of lithium in the presence of a catalytic amount of DTBB (10% molar), a double reductive cleavage takes place to give the dianionic intermediate VII , which by reaction with different electrophiles [H 2O, Me 2CO, Et 2CO, (CH 2) 4CO, (CH 2) 5CO], followed by hydrolysis with water, yields symmetrically 2,2′-disubstituted binaphthyls 8 and 11 . In the case of starting from ( R)- or ( S)-dihydrodinaphthoheteroepines 7 and 10 , these methodologies allow us to prepare enantiomerically pure compounds 8 , 11 and 12 .