Lithium-stabilized nucleophilic addition of thiamin to a ketone provides an efficient route to mandelylthiamin, a critical pre-decarboxylation intermediate

• Published in: Bioorganic chemistry Vol. 62; pp. 124 - 129
• Main Authors: Bielecki, Michael, Howe, Graeme W., Kluger, Ronald
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2015
• Subjects: Analysis; Benzoylformate; Chemistry Techniques, Synthetic; Equilibrium; Ketones - chemistry; Lewis Acids - chemistry; Lithium - chemistry; Lithium ion stabilization; Mandelic Acids - chemical synthesis; Nucleophilic carbene; Predecarboxylation intermediate; Protecting group; Synthesis; Thiamin; Thiamine - analogs & derivatives; Thiamine - chemical synthesis; Thiamine - chemistry; Nucleophilic carbene; Protecting group; Synthesis; Analysis; Predecarboxylation intermediate; Benzoylformate; Lithium ion stabilization; Equilibrium; Thiamin

[Display omitted] •Mandelylthiamin (MT) is a key pre-decarboxylation intermediate.•Condensation to produce esters of MT is thermodynamically controlled.•Lithium ions dramatically shift condensation toward product.•Isolated yield of MT is ∼50% vs <5% by previous routes.•Lithium-enhancement of addi...