Smith Lewis B, Armstrong Roly J, Hou Jingyan, Smith Edward, Sze Ming, Sterling Alistair J, Smith Alex, Duarte Fernanda, Donohoe Timothy J
Chemistry Research Laboratory, University of Oxford, OX1 3TA, Oxford, UK.
School of Natural and Environmental Sciences, Newcastle University, NE1 7RU, Newcastle Upon Tyne, UK.
Angew Chem Int Ed Engl. 2023 Sep 4;62(36):e202307424. doi: 10.1002/anie.202307424. Epub 2023 Jul 21.
An efficient synthesis of cyclohexenes has been achieved from easily accessible tetrahydropyrans via a tandem 1,5-hydride shift-aldol condensation. We discovered that readily available aluminium reagents, e.g. Al O or Al(O Bu) are essential for this process, promoting the 1,5-hydride shift with complete regio- and enantiospecificity (in stark contrast to results obtained under basic conditions). The mild conditions, coupled with multiple methods available to access the tetrahydropyran starting materials makes this a versatile method with exceptional functional group tolerance. A wide range of cyclohexenes (>40 examples) have been prepared, many in enantiopure form, showing our ability to selectively install a substituent at each position around the newly forged cyclohexene ring. Experimental and computational studies revealed that aluminium serves a dual role in facilitating the hydride shift, activating both the alkoxide nucleophile and the electrophilic carbonyl group.
通过串联的1,5-氢迁移-羟醛缩合反应，已从易于获得的四氢吡喃高效合成了环己烯。我们发现，易于获得的铝试剂，如Al O或Al(O Bu) 对该过程至关重要，它们能以完全的区域和对映体特异性促进1,5-氢迁移（这与在碱性条件下获得的结果形成鲜明对比）。温和的条件，再加上多种可用于获得四氢吡喃起始原料的方法，使这成为一种具有出色官能团耐受性的通用方法。现已制备了多种环己烯（>40个实例），许多为对映体纯形式，显示出我们能够在新形成的环己烯环周围的每个位置选择性地引入取代基。实验和计算研究表明，铝在促进氢迁移过程中起双重作用，既能活化醇盐亲核试剂，又能活化亲电羰基。
