Axially chiral biaryl dimethanols are ubiquitous and multifunctional intermediates for the synthesis of valuable atropisomeric molecules in advanced materials, drugs, natural products, and organocatalysts. Despite their broad synthetic utility, direct enantiodivergent catalytic access to this specific class of compounds remains largely unexplored, particularly in biocatalysis. Herein, we report a biocatalytic platform for enantiodivergent and atroposelective dynamic kinetic carbonyl reduction via transient seven-membered cyclic lactol intermediates. These engineered alcohol dehydrogenase (ADH)-driven transformations deliver up to 99% yield and enantioselectivity (>99:1 e.r. and < 1:99 e.r). This strategy demonstrates broad substrate compatibility, extending even to complementary “flipped” substrate series. Furthermore, the protocol is readily scalable to gram quantities and accommodates diverse downstream derivatizations. Mechanistic experiments and theoretical calculations delineate the pathway and illuminate the origin of enzymatic stereocontrol.
The enantioselective construction of boron-centered chirality remains a challenging topic in asymmetric catalysis. Although notable progress has been made in recent years, most existing strategies still rely on transition-metal catalysis, whereas organocatalytic approaches remain relatively scarce. Herein, we report...
Qing Yang, Jia-Hong Wu, Jingyu Ma et al.· ACS Catalysis· 0 citations
Chiral arylvinyl-substituted 3-hydroxy-5-oxo esters are valuable motifs in pharmaceuticals, yet their enantiocontrolled synthesis remains challenging. Herein, we report a biocatalytic system using ketoreductases (KREDs) for the highly C3-selective reduction of arylvinyl-substituted 3,5-dicarbonyl esters. Through semira...
Xiao-Qiu Wu, Ming-Yu Zhang, Ming-Yang Yao et al.· Organic Letters· 0 citations
ABSTRACT Chiral spirocyclopropyl heterocycles have emerged as privileged three‐dimensional structural motifs in medicinal chemistry. Nevertheless, efficient catalytic enantioselective assembly of such compounds still faces considerable synthetic difficulties. Herein, we describe a rhodium‐mediated asymmetric [2+1] cycl...
Yuanhao Zhu, Youzhi Xu, Weitao Zhang et al.· Advancement of science· 1 citation
Chiral allenes and alkynes are privileged scaffolds in natural products and pharmaceuticals. Although significant advances have been achieved in catalytic asymmetric synthesis from diazo compounds, selectively achieving high levels of both enantioselectivity and regioselectivity from the same starting materials remai...
Xin Ji, Yu-Hao Ni, Lu Yu et al.· Journal of the American Chem...· 0 citations
A general and practical enantioselective C-H activation/hydroarylation enabled by chiral transient directing groups (cTDGs) and ruthenium η-arene catalysts is reported, providing efficient access to benzo-fused six-membered heterocycles, including chiral chromanes, xanthenes, and related frameworks. It represents a rar...
Wei-Nan Tan, Nghia Le, Nguyen Tran et al.· Journal of the American Chem...· 0 citations
Heterohelicenes combine helical chirality with tunable electronic properties, making them attractive for applications in chiral materials and optoelectronics. However, their enantioselective synthesis, particularly for five-membered heterohelicenes, remains a long-standing challenge owing to the inherent synthetic di...
