pseudo Enantiomeric Carbohydrate Olefin Ligands – Case Study and Application in Kinetic Resolution in Rhodium(I)‐Catalysed 1,4‐Addition

Abstract

In order to investigate significant differences in asymmetric induction for pseudo enantiomeric carbohydrate olefin ligands in rhodium(I)catalysed 1,4-addition reactions, we designed a set of new olefin ligands differing in relative configuration and pyranoside conformation. With these, we have successfully elucidated structural requirements for metal binding and also identified an improved alternative for one pseudo enantiomer. Furthermore, we report the efficient kinetic resolution of a racemic 4-hydroxycyclopentenone derivative by 1,4-addition.Due to the increasing demand for chiral building blocks in natural product and medicinal chemistry, the design of new chiral ligands for asymmetric metal catalysis is an active research field. Chiral olefin ligands, [1] introduced independently by Hayashi [2] and Carreira, [3] are the ligands of choice for rhodium(I)mediated 1,4-additions of boronic acids to enones. [4] Carbohydrates are attractive, inexpensive starting materials for the design of novel ligands. [5] With gluco-enoPhos (1a, 1aa) [6] and galacto-enoPhos (psent-1a), [7] we have introduced a set of pseudo enantiomeric [8] olefin-phosphinite ligands derived from d-glucose and d-galactose (Scheme 1), giving 1,4-addition products in opposite configurations and typically above 90% ee. Significantly lower selectivity was observed for the gluco-ligands 1a and 1aa with bulky arylboronic and alkenylboronic acids, while high ees were retained with galacto-ligand ps-ent-1a. [7] This finding prompted us to investigate the origin of the differing asymmetric induction exerted by 1a and 1aa on the one hand and ps-ent-1a on the other hand, as well as to develop an improved alternative to gluco-ligands 1a and 1aa.An obvious explanation for the different efficiency of the gluco-ligands (1a, 1aa) and galacto-ligand (ps-Scheme 1. Ligands gluco-enoPhos (1a and 1aa) and galacto-enoPhos (ps-ent-1a): proposed coordination to Rh(I).

Synthesis of Chiral Cyclopentenones

“…Coordination of chiral alkene ligands to rhodium metal in the catalysis of 1,4-addition of boronic acids, as seen in the previous example, offers an excellent opportunity to control asymmetric induction through ligand design. Grugel et al sought to prepare novel alkene phosphinite ligands derived from carbohydrates, such as d -glucose and d -galactose . The authors studied structural constraints affecting enantioselectivity, such as the impact of axial versus equatorial positions for the ring substituents in the available pyranoside conformers.…”

“…Grugel et al sought to prepare novel alkene phosphinite ligands derived from carbohydrates, such as D-glucose and D-galactose. 56 The authors studied structural constraints affecting enantioselectivity, such as the impact of axial versus equatorial positions for the ring substituents in the available pyranoside conformers. Interestingly, it was found that the direction of asymmetric induction was primarily determined by the direction of the phosphinite substituent relative to the pyranoside ring (i.e., above or below).…”

Rh-catalyzed asymmetric 1,4-addition reactions to α,β-unsaturated carbonyl and related compounds: an update

“…The results are illustrated in Table 87. 263 Highly enantioselective additions of differently substituted arylboronic acids 2 to diverse b-nitro-based Michael acceptors 180a-i under the control of a novel and efficient Rh-bicyclo[2.2.1]-diene catalyst (S/C (substrate/catalyst) up to 1000) were successfully performed, affording b,b-diaryl nitroethanes 268a-z in good to high yields (62-99%) and with high to excellent enantioselectivities (85-97% ee) (Table 88). 264 This strategy was expanded to 2-heteroarynitroolefins and 2-alkylnitroolefins, which also gave the desired products with high enantioselectivities and yields via Rh-L50 complex catalysis.…”

Carbohydrates as enantioinduction components in stereoselective catalysis

“…The modularity of the ligand synthesis and the availability of different carbohydrate precursors allowed Boysen and co-workers to conduct extensive structure-activity studies, which also led to pseudo-enantiomeric ligand systems. 26 , 27 …”