Iron Catalytic Metal Carbene Insertion Reaction Of Oh Bond Research

Transition metal catalysis plays a crucial role in modern organic synthesis. The central metal of catalysts essentially determines the reactivity and selectivity of the reactions. Given its ready availability, low price, and environmentally friendly character, iron is an attractive and often advantageous alternative to other transition metals in the field of catalysis. Iron catalysts are drawing an increasing attention and undergoing an explosive growth recently. However, there are still many challenges remained in the iron catalysis. Firstly, the applications of iron catalysts are much less than that of the precious metal catalysts. Secondly, iron catalysts were generally less efficient comparing with other transition metal catalysts. Moreover, unlike other transition metals, which have achieved a great progress in the asymmetric catalysis in last decades, only a handful of iron-catalyzed asymmetric reactions reached beyond 90% enantiomeric excess. Thus, more highly efficient iron-catalyzed reactions are highly desired nowadays.In this context, an iron-catalyzed highly efficient carbenoid insertion into O-H bonds of water and alcohols has been developed. By using NaBAr_F as an additive, the insertion ofα-diazoesters into O-H bonds of water and alcohols has been accomplished efficiently, yieldingα-hydroxy and alkyloxylester derivatives in high yields (up to 98%). To the best of our knowledge, this is the best result of iron catalyzed metal-carbenoid O-H insertion reactions, which provides an efficient approach to the synthesis ofα-hydroxy and alkyloxylester derivatives.Furthemore, by using iron complexes of spiro bisoxazoline ligands, we have developed the first iron catalyzed asymmetric insertion ofα-diazoesters into O-H bonds of water and acohols, productingα-hydroxy and alkyloxyl ester derivatives in high yields with excellent enantioselectivities (up to 95% ee), which provides an efficient approach to the synthesis of chiralα-hydroxy and alkyloxyl ester derivatives.Additionaly, we have successfully applied this iron-catalyzed highly enantioselective O-H insertion reaction to the synthesis of Clopidogrel, a highly market-occupied platelet aggregation inhibitor.Ten new compounds were synthesized in this thesis. They were identified by ¹H NMR, ¹³C NMR, MS, HRMS or Elemental analysis.