A Striking Case of Enantioinversion in Gold Catalysis and Its Probable Origins

The cyclization of the hydroxy-allene 2 to the tetrahydrofuran 3 catalyzed by the gold-phosphoramidite complex 1, after ionization with an appropriate silver salt AgX, is one of the most striking cases of enantioinversion known to date. The major reason why the sense of induction can be switched from (S) to (R) solely by changing either the solvent or the temperature or the nature of the counterion X is likely found in the bias of the organogold intermediates to undergo assisted proto-deauration. Such assistance can be provided by a protic solvent, a reasonably coordinating counterion or even by a second substrate molecule itself; in this case, the reaction free energy profile gains a strong entropic component that can ultimately dictate the stereochemical course

One-Point Binding Ligands for Asymmetric Gold Catalysis: Phosphoramidites with a TADDOL-Related but Acyclic Backbone

Readily available phosphoramidites incorporating TADDOL-related diols with an acyclic backbone turned out to be excellent ligands for asymmetric gold catalysis, allowing a number of mechanistically different transformations to be performed with good to outstanding enantioselectivities. This includes [2 + 2] and [4 + 2] cycloadditions of ene-allenes, cycloisomerizations of enynes, hydroarylation reactions with formation of indolines, as well as intramolecular hydroaminations and hydroalkoxylations of allenes. Their preparative relevance is underscored by an application to an efficient synthesis of the antidepressive drug candidate (−)-GSK 1360707. The distinctive design element of the new ligands is their acyclic dimethyl ether backbone in lieu of the (isopropylidene) acetal moiety characteristic for traditional TADDOL’s. Crystallographic data in combination with computational studies allow the efficiency of the gold complexes endowed with such one-point binding ligands to be rationalized