Regiodivergent Addition of Phenols to Allylic Oxides: Control of 1,2‐ and 1,4‐Additions for Cyclitol Synthesis

Abstract

Control of 1,2- and 1,4-addition of substituted phenols to allylic oxides is achieved by intercepting palladium π-allyl complexes. The interconversion of palladium complexes results in the total synthesis of MK7607, cyathiformine B type, streptol, and a new cyclitol.

Synthesis of Natural O-Linked Carba-Disaccharides, (+)- and (−)-Pericosine E, and Their Analogues as α-Glucosidase Inhibitors

“…15:1. Gradual and careful addition of Oxone ® at −15 °C to a H 2 O–trifluoroacetone solvent system for in situ generation of TFDO was required in this process, otherwise the inseparable regioisomer was present in the product [ 12 , 28 , 33 ]. Details of reaction condition optimization can be found in our previous communication [ 15 ].…”

“…These natural products can reduce the antifungal activities of antibiotics. Another noteworthy synthesis is that of a pericosine analogue, along with cyathiformine B, streptol, and MK7607, using the regio- and stereo-controlled ring opening of allylic oxides reported by Lewis and co-workers [ 28 ]. These studies implied that the syntheses of pericosines will become increasingly important in the future.…”

Regiodivergent Addition of Phenols to Allylic Oxides

“…The origin of the products can be traced to the diastereomeric η 3 -allyl intermediate and stereoisomer of oxide employed. We have recently identified 3 a system capable of the conversion of racemic allylic oxides to distinct enantioenriched regioisomers using achiral phenol donors (Scheme 1). The allylic oxide regio-resolution (AORR) allowed the preparation of enantioenriched carbasugar natural products.…”

“…Prior to a full examination of chiral phenol structures with oxide 1 , a series of achiral phenol donors were studied using the developed predictive model. 3 The absolute stereochemistry of addition was determined using para -methoxyphenol under oxidative cleavage conditions. 3,4 The collected data was able to provide a working model for regiodivergence using ligand 4 5 with the donor phenols (Scheme 2).…”

“…3 The absolute stereochemistry of addition was determined using para -methoxyphenol under oxidative cleavage conditions. 3,4 The collected data was able to provide a working model for regiodivergence using ligand 4 5 with the donor phenols (Scheme 2). In parallel with Lloyd-Jones 6 and Trost’s 1d studies, a model was generated for oxide 1 that would be necessary for studying the AORR with complex phenol donors.…”