Axially chiral molecules bearing multiple stereogenic axes are of great importance in the field of organic chemistry. However, the efficient construction of atropisomers featuring two different types of stereogenic axes has rarely been explored. Herein, we report the novel atroposelective synthesis of configurationally stable axially chiral B,N-heterocycles. By using stepwise asymmetric allylic substitution-isomerization (AASI) strategy, diaxially chiral B,N-heterocycles bearing BÀ C and CÀ N axes that are related to the moieties of axially chiral enamines and arylborons were also obtained. In this case, all four stereoisomers of diaxially chiral B,Nheterocycles were stereodivergently afforded in high enantioselectivities. Density functional theory (DFT) studies demonstrated that the NH•••π interactions played a unique role in the promotion of stereospecific isomerization, thereby leading to the highly efficient central-toaxial chirality transfer.
Axially chiral N‐substituted quinazolinones are important bioactive molecules, which are presented in many synthetic drugs. However, most strategies toward their atroposelective synthesis are mainly limited to the axially chiral arylquinazolinone frameworks. The development of modular synthetic methods to access diverse quinazolinone‐based atropisomers remains scarce and challenging. Herein, we report the regio‐ and atroposelective synthesis of axially chiral N‐vinylquinazolinones via the strategy of asymmetric allylic substitution‐isomerization. The catalysis system utilized both asymmetric transition‐metal catalysis and organocatalysis to efficiently afford trisubstituted or tetrasubstituted N‐vinylquinazolinone atropisomers, respectively. With the meticulous design of β‐substituted allylic substrates, configurationally stable Z‐ and E‐tetrasubstituted axially chiral N‐vinylquinazolinones were obtained in good yields and high enantioselectivities.
Axially chiral molecules bearing multiple stereogenic axes are of great importance in the field of organic chemistry. However, the efficient construction of atropisomers featuring two different types of stereogenic axes has rarely been explored. Herein, we report the novel atroposelective synthesis of configurationally stable axially chiral B,N-heterocycles. By using stepwise asymmetric allylic substitution-isomerization (AASI) strategy, diaxially chiral B,N-heterocycles bearing BÀ C and CÀ N axes that are related to the moieties of axially chiral enamines and arylborons were also obtained. In this case, all four stereoisomers of diaxially chiral B,Nheterocycles were stereodivergently afforded in high enantioselectivities. Density functional theory (DFT) studies demonstrated that the NH•••π interactions played a unique role in the promotion of stereospecific isomerization, thereby leading to the highly efficient central-toaxial chirality transfer.
Axially chiral N‐substituted quinazolinones are important bioactive molecules, which are presented in many synthetic drugs. However, most strategies toward their atroposelective synthesis are mainly limited to the axially chiral arylquinazolinone frameworks. The development of modular synthetic methods to access diverse quinazolinone‐based atropisomers remains scarce and challenging. Herein, we report the regio‐ and atroposelective synthesis of axially chiral N‐vinylquinazolinones via the strategy of asymmetric allylic substitution‐isomerization. The catalysis system utilized both asymmetric transition‐metal catalysis and organocatalysis to efficiently afford trisubstituted or tetrasubstituted N‐vinylquinazolinone atropisomers, respectively. With the meticulous design of β‐substituted allylic substrates, configurationally stable Z‐ and E‐tetrasubstituted axially chiral N‐vinylquinazolinones were obtained in good yields and high enantioselectivities.
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