Chiral Macrocyclic Bis(oxazoline) Cu^I Complexes – Structure/Stereoselectivity Relationships in Catalytic Cyclopropanations

Abstract

The design and synthesis of 18 chiral macrocycles with built in C2‐symmetric bis(oxazoline) units is described and the catalytic properties of their copper(I) complexes in cyclopropanations of styrene with ethyl diazoacetate are assessed. The bridging of two homochiral centers in the bis(oxazoline) unit gives a macrocyclic ligand, which upon binding of CuI is transformed into a macrocyclic catalytic complex containing a chiral cavity. Such a complex represents a conceptually new type of supramolecular organometallic catalyst, possessing a chiral reaction cavity. A clear relationship between catalyst structures and the stereoselectivity outcome in the catalytic cyclopropanations has been established and it is demonstrated that both the enantioselectivity and the diastereoselectivity can be independently modified by variation of the ligand structural parameters. The CuI complex of the ligand 3b gave a trans/cis diastereomeric ratio of 94:6 (de = 88 %), representing the highest diastereoselectivity obtained to date for cyclopropanations catalyzed by the bis(oxazoline) class of complexes. An explanation of the observed relationship between stereochemical outcome and ligand structure is proposed.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Recent Applications of Oxazoline-Containing Ligands in Asymmetric Catalysis

“…These ligands were applied in the enantioselective cyclopropanation of styrene with diazoacetate, with ligand 141 giving a 7:93 cis:trans ratio, with enantioselectivities of 59-65% ee, respectively. 119 Du has reported the application of ligands 142 and 143, in which the two oxazoline rings are linked by a dibenzocycloheptadiene unit in the addition of diethylzinc to aldehydes (Scheme 1.41) and the palladium-catalyzed asymmetric allylic alkylation of dimethyl malonate (Scheme 1.6).…”

Chlorination of Aliphatic Primary Alcohols via Triphosgene–Triethylamine Activation

“…There is ample precedent for the conversion of reactive (i.e., benzylic, propargylic, and allylic) alcohols to the corresponding chlorides via triphosgene activation in pyridine-buffered organic media . Chlorination of simple aliphatic alcohols, however, requires stronger activation, most notably through the use of a nucleophilic promoter, such as triphenylphosphine that facilitates triphosgene decomposition and promotes the ensuing chlorination . Due to the unexpected propensity of triphosgene and triethylamine mixtures to chlorinate diol 1a , we believed this unexplored reaction warranted further investigation on its scope and limitations.…”

Update 1 of: C2-Symmetric Chiral Bis(oxazoline) Ligands in Asymmetric Catalysis

“…Since the benchmark of these homogeneous catalysts is [( S )- 2 /CuOTf] (Table , entry 1, 99% ee), the enantioselectivity promoted by Cu(I) or Cu(II) complexes of 7j , k , 7t , u , ,, 7v – x , 7af , 13a – c , e , and 14a – d , must be taken as the results of model catalysts. Recently several macrocyclic boxes of the general formula 14 and 15 have been synthesized, and 16 of them have been tested in the Cu(I)-catalyzed cyclopropanation of styrene with ethyldiazoacetate . The best catalyst proved to be that derived from box 14g .…”