Abstract
Hydrazones derived from cycloalkenones undergo an enantioselective transannular formal (3 + 2) cycloaddition catalyzed by a chiral phosphoric acid. The reaction provides high yields and excellent stereocontrol in the formation of complex adducts with one or two α-tertiary amine moieties at the ring fusion, and these can be converted into very versatile stereodefined decalin- or octahydro-1H-indene-derived 1,3-diamines through simple reductive N–N cleavage.
Highlights
Transannular reactions, in which two reacting sites are connected to each other as part of a medium- or largesize cyclic starting material, represent an unconventional strategic decision in organic synthesis that enables the rapid construction of complex polycyclic molecular scaffolds.[1]
There are many reports of elegant total syntheses that make use of transannular reactions to build up the key structural framework of the final target,[2] including several examples of biomimetic approaches that show that this type of reactivity is operating as part of the portfolio of chemical reactions in the secondary metabolism of living cells
Very recently, we demonstrated the excellent performance of catalytic transannular reactions in the enantioselective synthesis of complex polycyclic systems with the development of a transannular Morita−Baylis−Hillman reaction under chiral phosphine catalysis,[9] a Michael-initiated cascade reaction under bifunctional tertiary amine/squaramide catalysis,[10] and a copper-catalyzed transannular borylative ring-closing process.[11]
Summary
Obtained from adducts 2k and 2m with high enantio- and diastereocontrol. (See entries 4 and 6.). We have demonstrated the ability of hydrazones derived from cycloalkenones to undergo enantioselective transannular formal (3 + 2) cycloaddition under catalysis by a chiral Brønsted acid derived from BINOL This simple reaction provides stereodefined tricyclic adducts in high yields with high enantioselectivities, and these can be used as an ideal platform for the preparation of decaline- or octahydro1H-indene- derived 1,3-diamines with great potential to be used as synthetic intermediates or chiral ligands and that are otherwise challenging compounds to access through conventional methodologies. Efraim Reyes − Department of Organic and Inorganic Chemistry, University of the Basque Country (UPV/EHU), 48080 Bilbao, Spain; orcid.org/0000-0003-2038-9925. Liher Prieto − Department of Organic and Inorganic Chemistry, University of the Basque Country (UPV/EHU), 48080 Bilbao, Spain; orcid.org/0000-0001-7965-7168.
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