Stereocontrolled Synthesis of Oxaspirobicycles via Prins-Pinacol Annulation

Abstract

We have developed the stereoselective synthesis of 2-oxaspiro[m,n]alkane derivatives using the Prins-pinacol annulation of alkene diols with a wide range of aliphatic or aromatic aldehydes and ketones. This approach was further applied for the synthesis of oxatricyclic ring system.

Sequential Prins/Pinacol Strategy for the Stereoselective Synthesis of Spiro‐β‐tetralones

“…We assume that the reaction proceeds through the formation of oxocarbenium ion ( B , Scheme ), which is derived from the condensation of enediol 1 with aldehyde 2 under acidic conditions. A subsequent Prins cyclization of B resulting in the formation of C followed by pinacol rearrangement of C would give the desired spirocycle 3 . In the above cyclization, one can also expect the formation of D if the bond migrates from a six‐membered carbocycle.…”

2.03 Prins Reactions and Carbonyl, Imine, and Thiocarbonyl Ene Reactions

“…239 Cho synthesized a series of oxaspirobicycles by Prins-pinacol reactions. 240 For instance, treatment of 445 with an aldehyde and TMSOTf generates 446 in 65-81% yield (see Scheme 53). 240 Barriault generated bicyclo[m.n.1]alkanones by Prins-pinacol reactions.…”

“…240 For instance, treatment of 445 with an aldehyde and TMSOTf generates 446 in 65-81% yield (see Scheme 53). 240 Barriault generated bicyclo[m.n.1]alkanones by Prins-pinacol reactions. 241 For instance, treatment of 447 with TMSOTf opens the dioxolane to generate an alkoxonium ion, which cyclizes to a tetrahydropyranyl cation, which undergoes a 1,2-alkyl shift to form 448 in 87% yield.…”

Construction of Oxa‐Bridged Tetracyclic Frameworks through a Prins Bicyclic Annulation

“…Among them, Prins cyclization is one of the widely used strategies for the synthesis of tetrahydropyran derivatives under mild conditions with a high degree of stereoselectivity . In particular, an intramolecular version of this reaction provides a diverse range of fused/bridged/spirotetrahydropyran systems with high selectivity . The intermediate carbocation is trapped intramolecularly with different nucleophiles such as OH, ‐SH, Ar‐H and ‐CONH‐ groups .…”