Part I. N-Chlorinative ring contraction of 1,4-dimethoxyphthalazines Part II. Stereospecific syn-dichlorination of alkenes stereo-directing groups

Abstract

Part I. An unprecedented N-chlorinative ring contraction of 1,2-diazines was discovered and investigated with an electrophilic chlorinating reagent, trichloroisocyanuric acid (TCICA). Through optimization and mechanistic analysis, the assisting role of n-Bu4NCl as an exogenous nucleophile was identified, and the optimized reaction conditions were applied to a range of 1,4-dimethoxyphthalazine derivatives. Also, an improvement in overall efficiency was demonstrated by using a labile O-silyl group. A bicyclization/ring-opening mechanism was proposed and supported by the DFT calculations. Part II. syn-Stereospecific alkene dihalogenation draws attention as a long-standing problem in synthetic organic chemistry. In this study, convenient syn-dichlorination of alkenes was investigated via three strategies. The development of new phosphorus(V) dichloride reagents featuring a confined spatial arrangement of dichlorides by a tridentate ligand was proposed on the basis of the known syn-dichlorinating reactivity of PCl5. However, the preparation of various phosphorus(V) dichlorides was unsuccessful. Alternatively, a more straightforward approach would be the incorporation of an additional stereo-inverting step within the traditional anti-dihalogenation process. Several stereo-directing groups were examined, and a highly effective syn-dichlorination of N-protected allylic amines was developed via the anchimeric assistance phenomenon using 1,8-naphthalimide. The formerly unemployable aryl alkenes were syn-dichlorinated in excellent yields (>95%) and stereospecificity (>50:1). To further expand the scope and address the limitations of substrate, a traceless stereo-directing group strategy was also developed. Thianthrene was selected as a temporal nucleophile, and the anti-chlorothianation followed by the substitution of chloride resulted in a general, catalytic the syn-dichlorination of alkenes.