Diastereoselective Synthesis of 2-Amino-spiro[4.5]decane-6-ones Through Synergistic Photocatalysis and Organocatalysis for [3 + 2] Cycloaddition of Cyclopropylamines with Olefins

This research employs 2-methylene-tetrahydronaphtalene-1-ones and N-cyclopropylanilines as starting materials, integrating photocatalysis and organic phosphoric acid catalysis to synthesize 2-amino-spiro[4.5]decane-6-ones via a [3 + 2] cycloaddition approach. This method boasts the advantage of mild reaction conditions that are photocatalyst-free and metal catalyst-free. It achieves 100% atom conversion of the substrates, aligning with the principles of green chemistry. Additionally, it attains a high diastereoselectivity result of up to 99:1, demonstrating good stereoselectivity. In the derivatives of 2-methylene-tetrahydronaphtalene-1-ones, substrates with alkane rings of different sizes or thiophene replacing the phenyl ring are also amenable to this method, enabling the synthesis of different [4.4], [4.5], and [4.6] spirocyclic compounds. In the derivatives of N-cyclopropylanilines, substrates with para-fluoro and meta-fluoro substitutions are also amenable to this method. Finally, a preliminary mechanistic investigation was conducted, proposing a plausible reaction mechanism pathway initiating from the intermediate N-cyclopropylanilines with chiral phosphoric acid.