Novel Chiral Diamino‐Oligothiophenes as Valuable Ligands in Pd‐Catalyzed Allylic Alkylations. On the “Primary” Role of “Secondary” Interactions in Asymmetric Catalysis

Abstract

A new class of chiral C 2 -symmetrical diamino-oligothiophenes is described to be effective in catalyzing Pd-mediated asymmetric allylic alkylations in a highly enantioselective manner. The combination of experimental as well as crystallographic evidence revealed the key role played by sulfurbased heteroaromatic rings in the stereodiscriminating step of the procedure. In particular, unprecedented non-covalent secondary interactions between the inner thiophene and the metal center proved to be essential to create the stereochemical environment necessary in order to guarantee excellent levels of chemical and optical yields.Keywords: asymmetric catalysis; crystal structure; oligothiophenes; secondary interactions; palladium complexes Asymmetric organic as well as organometallic catalysis has blossomed into a mature field over the last decades.[1,2] Accordingly, the search for new chiral organic molecules effectively acting in the control of stereochemical outcomes of organic transformations is almost a daily task for numerous synthetic chemists.Oligothiophene molecular motifs are pivotal candidates in the molecular material scenario due to their remarkable electrical and optical properties. [3,4] Taking advantage of the extremely flexible coordination mode of the sulfur-containing five-membered rings, [5,6] much effort has also been devoted to the preparation and characterization of several metallo-oligo-and polythiophene hybrid materials.[7] The unique coordinating features in combination with their ready synthetic accessibility render chiral thiophene derivatives potential candidates as ligands also in the field of asymmetric organometallic catalysis. However, only a few examples of their application have been reported to date.[8]Herein, we describe our preliminary findings in the synthesis, structural characterization and application of a new class of C 2 -symmetrical diamino-oligothiophenes (3, DATs) [9] in the highly stereoselective Pd(0)-catalyzed asymmetric allylic alkylation (AAA) of malonates with both linear hindered and unhindered substrates.[10] Moreover, the presence of an intramolecular "secondary/weak" interaction [11] in the catalytic complex between one of the thienyl rings and the palladium center is discovered to play an active role in order to guarantee chemo-enzymatic levels of chemical as well as optical yields in the final product.A series of new chiral (R,R)-diamino-oligothiophenes (3) bearing one (T1), two (T2) or three (T3) thienyl units in each N-pendant, was prepared in high yields under mild conditions following the strategy depicted in Scheme 1. Scheme 1. Reagents and conditions: a) MgSO 4 , CH 2 Cl 2 , room temperature, 24 -48 h; b) NaBH 4 , MeOH, room temperature or NaBH 3 CN/HCl, THF/MeOH, 0 8C to room temperature for 3c.

Controlling Stereochemical Outcomes of Asymmetric Processes by Catalyst Remote Molecular Functionalizations: Chiral Diamino‐oligothiophenes (DATs) as Ligands in Asymmetric Catalysis

“…Crystallographic evidence on [Pd(η 3 ‐C 3 H 5 )( 3 b )] + provided insight into the role of thiophene rings in the stereochemical outcome of the process. In particular, one inner thiophene was found to interact attractively with the transition‐metal center [S2⋅⋅⋅Pd 3.34(1) Å] 13. On the basis of the experimental findings previously reported,13 we hypothesized the presence of such a hemilabile contact16 in solution also, dynamically bringing the oligothienyl side arm closer to the catalaphoric unit with increased overall stereodifferentiation.…”

“…In particular, one inner thiophene was found to interact attractively with the transition‐metal center [S2⋅⋅⋅Pd 3.34(1) Å] 13. On the basis of the experimental findings previously reported,13 we hypothesized the presence of such a hemilabile contact16 in solution also, dynamically bringing the oligothienyl side arm closer to the catalaphoric unit with increased overall stereodifferentiation. It is noteworthy that AAA processes have already proven to be strongly affected in solution, even by “weak/secondary” intramolecular contacts between side arms of the ligand and metal center 17…”

“…In the course of our continuing efforts to develop new chiral organometallic catalysts for enantiodiscriminating transformations, we reported recently on the synthesis of a family of chiral C 2 ‐symmetric multidentate diamino‐oligothiophenes (DATs, 3 a , b ) 13. 14 DATs were readily obtainable through reductive amination of commercially available ( R , R )‐1,2‐cyclohexanediamine ( 1 ) by the corresponding thienyl (T) aldehydes 2 a , b (Scheme ).…”

“…We have reported recently the synthesis, chemo‐optical characterization, and catalytic properties of a new family of chiral ligands containing oligothienyl systems (diamino‐oligothiophenes, DATs) that proved effective in the stereoselective Pd‐catalyzed asymmetric allylic alkylation (AAA)12 of allylcarbonates 13…”

New adaptive chiral thiophene ligands for copper‐catalyzed asymmetric Henry reaction

“…In this field, we recently reported on the effectiveness of a new family of chiral C2-symmetric diamino ligands, bearing oligothienyl groups of various lengths, in several asymmetric transformations such as allylic alkylation, 6,7 hydrosylilation of ketones, 8 and Henry condensations (Fig. 1).…”