JoyaPhos: An Atropisomeric Teraryl Monophosphine Ligand

Abstract

At opologically well-defined atropisomeric teraryl monophosphine ligand system, prepared by ah ighly stereoselective arene-forming aldol condensation combined with ad irect ester-to-anthracene transformation, is described herein. The ligands were evaluated for gold(I)catalyzed [2+ +2] cycloadditiona nd cycloisomerization reactions as well as au nique intramolecular Pd-catalyzedC ÀN cross-coupling for the atroposelective synthesis of a Naryl-indolineb earing aC ÀNs tereogenic axis. The ligand structure induced up to 95:5 stereoselectivity in the asymmetric allylic alkylation reaction and features an interesting dynamic behavior as observed by X-ray crystallographic studies.

Catalyst Control over Twofold and Higher-Order Stereogenicity by Atroposelective Arene Formation

“…Since ligands with atropisomeric axes find widespread application in transition metal catalysis, it appeared predestined to employ the aldol condensation strategy to construct configurationally stable biaryls for their use as ligands in stereoselective catalysis. The atropisomeric JoyaPhos ligands, which were introduced lately, are configurationally and bench-stable teraryl monophosphines and were obtained in high enantiomeric purity by this strategy …”

“…Both Cy 2 JoyaPhos ( 17a ) and Ph 2 JoyaPhos ( 17b ) provided 19 with high e.r. in excellent yield . In addition, the JoyaPhos ligands were successfully employed in Au­(I)- and other Pd(0)-catalyzed reactions (Scheme ).…”

“…The atropisomeric JoyaPhos ligands, which were introduced lately, are configurationally and benchstable teraryl monophosphines and were obtained in high enantiomeric purity by this strategy. 56 The substrate for the arene-forming aldol condensation, the key step in the preparation of JoyaPhos ligands (Scheme 3), was prepared by IBX oxidation of 13. The latter was expediently synthesized from 2-bromobenzaldehyde (11) and the mixedmetal organometallic building block 12.…”

“…in excellent yield. 56 In addition, the JoyaPhos ligands were successfully employed in Au(I)-and other Pd(0)-catalyzed reactions (Scheme 4). 56 While the synthetic aldol condensation reactions described above form one aromatic ring, PKSs often catalyze the simultaneous construction of multiple aromatic rings from polyketone substrates.…”

Catalytic Cascade Reactions Inspired by Polyketide Biosynthesis

“…[48] Gratifyingly, the products emerging from the small molecule-catalyzed noncanonical polyketide cy-forming aldol condensation, we next assessed the well-defined topology of the explored atropisomers for the design of a new class monophosphine ligands named JoyaPhos (Scheme 4). [40] The synthesis of the JoyaPhos ligands commences by the building block addition [28,41] to 2-bromobenzaldehyde. After an in situ oxidation and a stereoselective arene-forming aldol condensation, a subsequent functional group interconversion provided the enantiomerically enriched carboxylic acid ester with an 99:1 enantiomeric ratio, which serves as optimal precursor for an ester-to-anthracene transformation which we previously developed.…”