Au‐Cavitand Catalyzed Alkyne‐Acid Cyclizations

Abstract

Supramolecular cavitands that contain inwardly directed functional groups have yielded specialized transformations and trapping of reactive intermediates. A recently reported 3‐wall Au cavitand provides exciting opportunities for supramolecular catalysis. In this study, a variety of substituted γ‐alkynoic acids were reacted to give lactones. The interaction of peripheral “R” groups revealed differential catalyst behavior. Extremely large and small groups reacted with appreciable rate. Intermediate sized groups however, slowed significantly: giving support that size‐specific binding is at play when using cavitands as a scaffold for gold catalysis. These results serve as some of the first evidence of the interplay between substrate and cavitand interior in the catalytic sphere.

Enantioselective Alkoxycyclization of 1,6‐Enynes with Gold(I)‐Cavitands: Total Synthesis of Mafaicheenamine C

“…Zuschriften 9428 www.angewandte.de studies of the two possible transition states show attractive interactions between the cavitand and the aromatic ring of the enyne and non-covalent interactions within the complex itself in TS I-II , which are weaker in TS III-IV . [29] To sum up, we have designed a new family of achiral and chiral gold(I)-cavitand complexes, easily synthesized in either enantiomeric form in a modular manner from resorcin- [4]arenes and commercially available chiral secondary amines. While new selectivity was uncovered in the cyclization of dienynes with achiral gold(I)-cavitand complexes, the chiral catalysts allowed to develop an enantioselective alkoxycyclization of 1,6-enynes, which has been applied for the first total synthesis of (+)and (À)-mafaicheenamine C, assigning the absolute configuration of the natural compound.…”

“…The design of supramolecular entities that mimic the activity of enzymes is an attractive approach for enhancing the selectivity of metal catalysts. [1] In this regard, gold(I) cavitands based on resorcin [4]arene skeletons have been applied for cross-dimerization [2] and hydration of alkynes, [3] cyclization of alkynyl carboxylic acids, [4] and intramolecular arenealkyne reactions. [5] However, gold(I) cavitands have not yet been applied in the context of more challenging asymmetric transformations.…”

“…We explored the prospect of achieving enantioselectivity in gold(I) catalysis by employing gold(I) complexes with chiral resorcin [4]arene phosphoramidite as ligands (Scheme 1). Specifically, our aim was to enantioselectively activate 1,6-enynes with terminal alkynes in reactions with alcohols (alkoxycyclization) to form 1-methylene-2,3-dihydro-1H-indenes, whose oxidative cleavage would furnish synthetically useful chiral indanones.…”

Enantioselective Alkoxycyclization of 1,6‐Enynes with Gold(I)‐Cavitands: Total Synthesis of Mafaicheenamine C

“…NCI plot Angewandte Chemie Communications studies of the two possible transition states show attractive interactions between the cavitand and the aromatic ring of the enyne and non-covalent interactions within the complex itself in TS I-II , which are weaker in TS III-IV . [29] To sum up, we have designed a new family of achiral and chiral gold(I)-cavitand complexes, easily synthesized in either enantiomeric form in a modular manner from resorcin- [4]arenes and commercially available chiral secondary amines. While new selectivity was uncovered in the cyclization of dienynes with achiral gold(I)-cavitand complexes, the chiral catalysts allowed to develop an enantioselective alkoxycyclization of 1,6-enynes, which has been applied for the first total synthesis of (+)and (À)-mafaicheenamine C, assigning the absolute configuration of the natural compound.…”

“…Specifically, our aim was to enantioselectively activate 1,6-enynes with terminal alkynes in reactions with alcohols (alkoxycyclization) to form 1-methylene-2,3-dihydro-1H-indenes, whose oxidative cleavage would furnish synthetically useful chiral indanones. Herein, we report an enantioselective alkoxycyclization of 1,6-enynes by using chiral mono-cationic gold(I) resorcin [4]arene phosphoramidite complexes as catalysts. To demonstrate their potential, we have completed the first total synthesis of (+)-mafaicheenamine C as well as its non-natural enantiomer, establishing the absolute configuration of the natural product.…”