Construction of C-C bonds is the basis of organic chemistry. Designing organic molecules capable of catalyzing efficient and stereoselective C-C bond formation is a formidable challenge, which is why this area of research is getting substantial attention. The field of organocatalysis has provided a significant boost to the development of new stereoselective methods for C-C bond formation. Chiral 1,2-diamines are privileged structural motifs in organic synthesis and are widely used in stereoselective (organo)catalysis. The most versatile type of organocatalysts are bifunctional amino-thioureas and amino-squaramides. These catalysts are based on a limited set of chiral structural scaffolds with 1,2-diamine moiety as a common structural motif, while highly efficient 1,3- and 1,4-diamine derived organocatalysts are very rare (exception being (BINAM)-based organocatalysts). Development of new organocatalytic scaffolds is promoted by the synthesis of new chiral diamines from chiral pool molecules. Camphor is one of nature’s privileged scaffolds and its reactivity can be utilized for the preparation of novel chiral diamines. With proper functional decoration they can be converted into corresponding (organo)catalysts. We herein report the synthesis of a novel type of camphor-based 1,3-diamines and their use in asymmetric Michael additions as squaramide-derived organocatalysts. Catalyst <b>I</b> shows excellent conversions and enantioselectivities (up to &gt;99%) in 1,4-additions of 1,3-dicarbonyls to <i>trans</i>-β-nitrostyrene acceptors. Kinetic measurements support a bifunctional reaction mechanism and DFT calculations suggest that the reaction undergoes under Takemoto’s pathway. This seems to be the first time when the original mechanistic proposal seems to be working. This is surprising since the alternative Pápai-Soós pathway seems to be dominant for 1,2-diamino-derived catalysts.

Camphor-derived 1,3-diamine bifunctional organocatalysts

253rd National Meeting (2017)

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