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

Abstract

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.

Dimeric TADDOL Phosphoramidites in Asymmetric Catalysis: Domino Deracemization and Cyclopropanation of Sulfonium Ylides

“…As shown, the class of TADDOL-derived phosphoramidites L13-L16,f irst employed in gold catalysis by Fürstner and co-workers, [12] gave the highest reactivity (enabling full conversion within af ew hours) and good enantiomeric ratios.…”

Enantioselective Gold-Catalyzed Synthesis of Heterocyclic Compounds

“…One example is the use of a TADDOL-based phosphoramidite gold complex for the synthesis of indolines, pyrrolidines, and tetrahydrofurans by Fürstner et al [69]. In addition to the modularity provided by a convergent catalyst synthesis, this system was attractive as only one gold atom is required to accomplish previously published transformations with similar levels of conversion and enantioselectivity.…”

“…This methodology has been applied to the synthesis of the triple reuptake inhibitor GSK1360707 first by Elitzin et al and later by Fürstner and coworkers with (R)-DM-BINAP and TADDOL-based phosphoramidite ligands, respectively [103,104] A significant improvement in synthesis of these heterocycles came through the use of TADDOL-based phosphoramidite ligands by Fürstner et al [69]. Substituted tetrahydropyridines and dihydropyrans were obtained with up to 98% ee.…”

“…Additional pyrrolidine products with fused cycloheptadiene rings were synthesized in a follow-up work by Mascareñas et al using the same catalyst system [109]. In 2012, Fürstner and coworkers showed TADDOL-based phosphoramidite gold complexes were also competent catalysts for this reaction, achieving greater than 90% ee [69,110]. In 2007, Toste et al reported the first asymmetric cycloisomerization of an allenene substrate to form a cyclobutane-fused pyrrolidine product in 70% yield and 54% ee [111].…”

“…Vinyl gold attack of the benzylic cation then results in formation of the cyclobutane ring. Fürstner and coworkers succeeded in improving the enantioselectivity to 95% using a TADDOL-based phosphoramidite ligand [69,110]. A more detailed study by Toste et al in 2011 showed that a variety of enantioenriched products can be synthesized using a SPINOL-based phosphoramidite ligand (Scheme 27) [112].…”