Organocatalytic asymmetric chlorinative dearomatization of naphthols

Abstract

A highly enantioselective chlorinative dearomatization of 1-naphthol and 2-naphthols was realized for the first time, providing chiral naphthalenones with a Cl-containing all-substituted stereocenter in excellent yields and enantioselectivity (up to 97% yield and 96% ee).

Catalytic Strategies for the Asymmetric Construction of Cyclic Frameworks with a Halogenated Tetrasubstituted Stereocenter

“…Notably, the catalyst was speculated to provide a bifunctional catalysis model, in which the phthalazine nitrogen moiety enhanced the nucleophilic property of the naphthol through a hydrogen bond interaction, and the tertiary amine served as a Lewis base to activate the chloronium species. The established dearomative chlorination protocol was also suitable for methyl 1‐hydroxy‐2‐naphthoate 32 by using another similar catalyst C5 (DHQD) 2 PYR, and excellent yields and enantioselectivities were obtained (Scheme b) …”

Organocatalyzed Assembly of Chlorinated Quaternary Stereogenic Centers

“…The enantioselective chlorinative dearomatization of naphthols has also been achieved by employing ac inchonined erivative, namely,the commercially available 1,4-phthalazinediyl diether hydroquinidine [(DHQD) 2 PHAL, 8,F igure 4]. [12] The protocol allowed the preparation of enantioenriched naphthalenones that have achlorine atom at aquaternary center. The reaction proceeded smoothly at low temperature (À78 8C) by using 1,3-dichloro-5,5-dimethylhydantoin (DCDMH)a st he chlorinating agent.…”

“…Several2 -naphtholsw ere transformed by means of this method( Scheme 4). [12] The chlorination was successfulw ith 1-hydroxy-2-naphthoate, although ad ifferent solvent (CHCl 3 /CCl 4 = 1:1) was needed. The synthetic utility of these products was shown by using them in different transformations to render highly functionalized tetralones.…”

Regioselective Oxidative Chlorination of Arenols Using NaCl and Oxone

“…Since the 1950s, various electrophilic chlorinating systems including isocyanuric chloride, N ‐chlorosuccinimide (NCS), SO 2 Cl 2 , t BuOCl, NaOCl, SbCl 5 , SbF 5 –CH 2 Cl 2 and hypervalent iodine compounds have been developed for the chlorinative dearomatization of phenols . Recently, the enantioselective chlorinative dearomatization of naphthols has also been developed using 1,3‐dichloro‐5,5‐dimethylhydantoin (DCDMH) . The development of an efficient method for the chlorinative dearomatization of arenols using less‐toxic and inexpensive chlorinating reagents is still needed.…”