Titanium() enolates of cyclic ketones - stereoselective addition of cyclododecanone to aromatic aldehydes

• Published in: New journal of chemistry Vol. 47; no. 35; pp. 1655 - 16517
• Main Authors: Cie, Dariusz, Pa asz, Aleksandra, Kozie, Krzysztof, Lutsan, Antonii, Kalinowska-T u cik, Justyna
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 11.09.2023; Royal Society of Chemistry
• Subjects: Aldehydes; Aromatic compounds; Carbonyl compounds; Carbonyls; Chemistry; Chemistry, Multidisciplinary; Dehydration; Ketones; Low temperature; Physical Sciences; Science & Technology; Stereoselectivity; Titanium; MAGNESIUM-OXIDE; ASYMMETRIC ALDOL ADDITIONS; ACETONE; CONDENSATION; AMINE; CATALYSTS; BASE
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/d3nj02355a

Titanium( iv ) enolates of cyclododecanone (CDD) were investigated as convenient CH-acidic units for stereoselective aldol additions to various benzaldehydes leading to β-hydroxy carbonyl compounds. Aldol reactions were carried out at low temperatures, below −40 °C, which allowed minimizing the processes of dehydration and formation of enones. In contrast to alkali metal enolates that produced mainly anti -aldols, titanium( iv ) enolates of CDD tend to favor syn -stereoselectivity. Studies showed that the stereoselectivity of aldolization depended on the size and location of substituents in the aromatic ring of benzaldehydes used. The strongest effect was exerted by substituents in ortho and meta positions, while para -substituted benzaldehydes were characterized by stereoselectivity comparable to that of unsubstituted benzaldehydes. The presented work is so far the only method of synthesizing syn aldols from cyclododecanone in a one-step reaction. The application of the "soft enolization technique" led to the first synthesis of syn aldols from cyclododecanone titanium( iv ) enolates and aromatic aldehydes.