Phosphinite Thioglycosides Derived from Natural d-Sugars as Useful P/S Ligands for the Synthesis of Both Enantiomers in Palladium-Catalyzed Asymmetric Substitution

Abstract

Phosphinite thioglycosides I for which a modular synthetic approach is reported, were found highly efficient catalyst precursors for palladium(0)-catalyzed asymmetric substitution. Both enantiomers of the allylated products have been obtained with high ee (up to 96%) using natural sugars as catalyst precursors.Key words: P/S ligands, carbohydrates, both enantiomers, allylic substitutionThe difficulty to predict the structural requirements of a ligand for acting as a successful catalyst explains the enduring need to develop new ligands which combine efficiency, wide scope and easy synthesis.1 Therefore, modular synthetic designs allowing a rapid optimization of the ligand structure for a high activity and/or selectivity in a precise chemical transformation are greatly desirable. Carbohydrates, which are amongst the cheapest and most abundant chiral starting materials, hold a range of structural characteristics that make them very appealing for such venture.2 Notably, carbohydrates possess various hydroxyl groups in different orientations, allowing easy tuning of steric, electronic and three-dimensional structure of carbohydrate based ligands.3 Conceptually, the utilization of carbohydrates in asymmetric synthesis is severely limited when both enantiomers are needed, as Lsugars are exceedingly expensive. While this problem has been elegantly solved by RajanBabu 4 in the case of homodonor P/P ligands, up to now there is no solution in the case of mixed ligands with two different heteroatoms.Following the seminal work of Evans, 5 in this communication we report the first synthesis of mixed P/S ligands I derived from carbohydrates (Scheme 1), and their preliminary applications in a highly enantioselective palladium(0)-catalyzed allylic substitution. In our approximation both enantiomers of the allylated products have been obtained using pseudo-enantiomeric natural sugars as catalyst precursors. 6A fundamental characteristic of the phosphinite thioglycoside I is that upon coordination to the metal the anomeric sulfur atom becomes stereogenic. The close proximity of the chiral sulfur atom to the coordination sphere of the transition metal anticipates a good enantioselective discrimination in the catalytic process, provided that the low inversion barrier of the sulfur metal bond can be surmounted. 5,7 We have recently reported the preparation of C 2 -symmetric bis-thioglycosides as new homodonor S/S ligands in Pd(0)-catalyzed allylic alkylation of 1,3-diphenylpropenylacetate with dimethyl malonate.8 A subsequent study of the corresponding Pd(II) complexes has indicated that the good enantioselectivity achieved was a consequence of an efficient stereocontrol of the sulfur atom exerted by the exo-anomeric effect. 9 In the case of phosphinite thioglycosides I metal complexes, where the exo-anomeric effect is not operative, good stereocontrol of the sulfur atom is also predicted taking into account the strong steric and stereoelectronic interactions of the substituent at sulfur and the endocyclic oxygen of the py...

Studies on the diastereoselective oxidation of 1-thio-β-d-glucopyranosides: synthesis of the usually less favoured RSsulfoxide as a single diastereoisomer

“…We have recently found that in the case of sterically hindered tert-butanethiol the thioglycosilation takes place under thermodynamic control, being the α-thioglycoside the more stable isomer. 22 Similarly, and in order to obtain the kinetic isomer, the reaction was conducted at 0ºC affording the desired product 4 in 70% yield as a white solid.…”

Pseudo enantiomeric mixed S/P ligands derived from carbohydrates for the 1,4-addition of phenyl boronic acid to cyclohexenone

“…22 This stereocontrol coupled with the higher trans effect of phosphorus vs. sulfur 23 led to the discovery, of ligands 1 and 2 derived from D-sugars galactose and arabinose as excellent catalyst precursors for the synthesis of L-and D-amino esters, Scheme 1.…”

“…[a] 20 D : +13. 9 (c. 0.6,CHCl 3 (d,J ¼ 18.3 Hz),129.4 (d,J ¼ 51.4 Hz),128.7,128.6,128.5,128.4,128.3,128.2,126.1,101.8 (CHPh) (11).…”

Carbohydrates as enantioinduction components in stereoselective catalysis

“… 36 Interestingly, ligation of 28 to a Pd-centre afforded selectively a single diastereomer, resulting from preferential coordination of one of the two diastereotopic sulfur lone pairs. 36 , 37 This system was evaluated in Pd-catalysed AAA of dimethylmalonate with ( E )-1,3-diphenylallyl acetate ( 29 ) and gave 30 in high yield and 92% ee. The synthesis of a pseudo-enantiomeric version of 28 , where a d -arabinose core was used to invert the stereo-relationship between the S and P groups, was also described.…”

“…The synthesis of a pseudo-enantiomeric version of 28 , where a d -arabinose core was used to invert the stereo-relationship between the S and P groups, was also described. 36 Both systems were also evaluated in asymmetric Rh-catalysed hydrogenations of enamides.…”