C₁‐Symmetric Bicyclo[2.2.2]octa‐2,5‐diene (bod*) Ligands in Rhodium‐Catalyzed Asymmetric 1,4‐Addition of Arylboronic Acids to Enones and 1,2‐Addition to N‐[(4‐Nitrophenyl)sulfonyl]imines

Abstract

A set of ten C1‐symmetric chiral bicyclo[2.2.2]octa‐2,5‐dienes (bod*) 2 (Fig. 1) were tested as ligands in Rh‐catalyzed arylation reactions. The 1,4‐addition of arylboronic acids to cyclohex‐2‐en‐1‐one, cyclopent‐2‐en‐1‐one, and tert‐butyl cinnamate proceeded smoothly with excellent enantioselectivities (up to 99% ee; Tables 1–3). The challenging 1,2‐addition of triphenylboroxine to N‐[(4‐nitrophenyl)sulfonyl]imines yielded the product in high yield and in good enantioselectivity (up to 92% ee; Table 4). Generally, the use of C1‐symmetric chiral bod* ligands bearing bulky substituents resulted in lower enantioselectivities, whereas several electron‐poor and electron‐rich bod* ligands gave higher enantioselectivities than the benchmark ligands reported in literature.

4,8‐Disubstituted Bicyclo[3.3.1]nona‐2,6‐dienes as Chiral Ligands for Rh‐Catalyzed Asymmetric 1,4‐Addition Reactions

“…In diene‐Rh catalyzed arylations excess of aryl boronic acid (typically two equivalents) is necessary in order to achieve high yields. This requirement for use of excess arylboronic acid was attributed to the competing protodeboronation1b and homocoupling7g side reactions. From this point of view, the high catalytic activity of the Rh/ 4b complex is noteworthy – in the presence of 0.5 mol‐% of the catalyst, 3‐phenylcyclohexanone ( 7aa ) was obtained in 93 % yield and 95 % ee (Table 2, entry 21, compare with entry 1) with only 1.2 equiv.…”

“…In terms of both catalytic activity and enantioselectivity chiral dienes often surpass other types of ligands, such as chiral bisphosphines, especially in the conjugate addition of boronic acids to α,β‐unsaturated carbonyl compounds and arylation of imines,6–11 as well as other synthetically useful asymmetric rhodium‐catalyzed reactions 12. Nevertheless, even though diene–Rh catalyzed arylation reactions are conducted under milder conditions, in order to achieve high yields an excess of aryl boronic acid is generally required as a result of competing protodeboronation1b and homocoupling7g side reactions. The multistep synthesis and, most notably, the necessity to use preparative chiral HPLC to access enantiomerically pure dienes or their synthetic precursors7c,9 also remains a concern.…”

Daring the Challenge and Thinking Big: The Value of Early Process R&D

“…This set of ten C1-symmetric chiral bicyclo[2.2.2]octa-2,5-dienes has been tested as ligands in four Rh-catalyzed arylation reactions: 1,4-addition to cyclopentenone, cyclohexenone, and tert-butyl cinnamate, and the 1,2-addition to N-[(4nitrophenyl)-sulfonyl]imines. [24] Scheme 16 depicts one of these reactions, the challenging 1,4-addition of arylboronic acids to tert-butyl cinnamate 31 that smoothly afforded the diphenylmethine 32 in high ee. Several of the novel dienes (30) gave higher enantioselectivities than the benchmark ligands reported in the literature.…”

A Chiral Disulfoxide Ligand for the Efficient Rhodium‐Catalyzed 1,2‐Addition of Arylboroxines to N‐Tosylarylimines

“…To extend the reactivity of our binaso‐type family of disulfoxides, we herein report the employment of these C 2 ‐symmetric S‐chiral disulfoxide ligands in the 1,2‐addition of arylboroxines to N ‐tosylaldimines. At the outset of this study, it was not clear whether these ligands would be successful in the 1,2‐addition, as it is well known that ligand requirements between the 1,4‐addition to α,β‐unsaturated compounds and the 1,2‐addition to imines are different and distinct and very few examples exist where the same ligand is able to promote both these reactions ,,,. Indeed, the report here is the first that shows that a disulfoxide ligand system can be used in the 1,2‐addition reaction.…”