Application of S,N-Chelating Chiral Zinc Bis(aminoarenethiolates) as New Precursor Catalysts in the Enantioselective Addition of Dialkylzincs to Aldehydes

Abstract

A new enantiomerically pure S,N-chelated zinc bis(aminoarenethiolate), (R,R)-Zn(SC 6 H 4 C-(Me)HNMe 2-2) 2 ((R,R)-3b), has been synthesized by the reaction of the (R)-trimethylsilyl aminoarenethiolate species (R)-2b with ZnCl 2 in a 2:1 molar ratio. (R,R)-3b is an efficient catalyst for the addition of dialkylzinc compounds to aliphatic and aromatic aldehydes to give the corresponding secondary alcohols in nearly quantitative yields with optical purities of 69-99% ee under mild reaction conditions. Although excellent selectivities were obtained with this simple ligand containing only one stereogenic (carbon) center, further modifications of the amino substituents were studied. Cyclic N(CH 2) 4 or N(CH 2) 5 amino-substituted aminoarenethiolate ligands considerably enhanced the reaction rates, resulting in shorter reaction times and higher ee's. The mechanism of these 1,2-addition reactions has the general characteristics as reported by Noyori et al. This conclusion is based on the synthesis, isolation, and characterization (X-ray, 1 H and 13 C NMR) of the enantiopure zinc bis-(aminoarenethiolate) and organozinc aminoarenethiolate intermediates and on monitoring of the reaction process. We present evidence for an interpretation of the binding in the product-forming key intermediate complex in terms of an organozinc cation/anion pair. The possibility that the very efficient transfer of chiral information in this compact complex may be due to a combination of the shortness of the Zn-N coordinate bonds with concomitant η 2 bonding of the aldehyde substrate is discussed. The solid-state structure of the zinc bis-(aminoarenethiolate) (R,R)-Zn(SC 6 H 4 C(Me)HNMe 2-2) 2 is reported.

Synthesis of Arylzinc Thiolates Containing Perfluoroalkyl Chains. Model Catalyst Precursors for the Enantioselective Zinc-Mediated 1,2-Addition of Dialkylzincs to Aldehydes in Fluorous Biphase Systems

“…This topic has been reviewed recently. 1 Previously, we 4 and others 5 have shown that chiral o-aminoarenethiolates are excellent catalyst for the enantio-selective addition of dialkylzincs to aldehydes. It is thus a challenge to modify these catalyst in such a way that they become applicable in FBS.…”

Enantioselective dialkylation of 1,2-phthalicdicarboxaldehyde

“…chiral bisphosphines, 2,3 which can be used as ligands in asymmetric catalysis. 4 The zinc-mediated addition of alkylzinc compounds to aldehydes, using chiral amino alcohols 5 or amino thiols 6,7 as catalyst precursors, affords the corresponding alcohols in high enantiomeric purity and high chemical yield. Recently, this methodology has been applied to the synthesis of C 2 -symmetric diols derived from terephthaldehyde and isophthaldehyde using (1S,2R)-DBNE 1 or (1S,2R)-PHONE as catalyst precursors.…”

“…) and the aminoarenethiolate-based catalyst precursors (2-3b 6,7 ) (see Fig. 1) were applied in this reaction.…”

“…This observation can be explained by: (i) an enhancement of the differences in relative thermodynamic stabilities of the intermediates that are formed during this reaction, and (ii) an enhanced rate of the transfer of the alkyl group from zinc to the substrate (for a discussion see Ref. 7). The importance of the latter factor appears from the observation that the uncatalyzed reaction of Et 2 Zn with 1,2-phthalicdicarboxaldehyde to lactol 4 needs about 18 h for completion.…”

“…Moreover, this methodology allows the introduction of two different organic groups at two adjacent benzylic positions. Since both enantiomers of the applied chiral amino-arene thiolate catalyst are available, 7 there is complete control over the absolute stereochemistry of the chiral target molecule. .…”