A highly efficient and accessible synthesis of chiral 3-substituted isoindolinone frameworks is described. The synthesis involved the Rh(I)-catalyzed asymmetric arylation of boronic acids to 2-halobenzaldimines and the subsequent Rh(I)-catalyzed intramolecular aminocarbonylation of the resulting 2-halobenzylamines using an aldehyde as the carbonyl source. The method tolerates a variety of functional groups, yielding isoindolinone derivatives in moderate to high yields with high ee-values. In addition, two Rh(I)-catalyzed transformations could be efficiently accomplished in a one-pot sequence to give chiral isoindolinones by the simple addition of a ligand and an aldehyde after the Rh(I)-catalyzed asymmetric arylation.

Optically active glyceraldehyde acetonide (II) is employed for the Rh‐catalyzed cyclocarbonylation of various enynes to produce bicyclic cyclopentenone derivatives.

Catalytic cyclocarbonylation reactions using a glyceraldehyde derivative as a carbonyl source are described. The rhodium(I)-catalyzed reaction of enynes with glyceraldehyde acetonide gave bicyclic cyclopentenones as the products. This presents an interesting use of a sugar alcohol derived carbon resource as well as a convenient procedure for the cyclocarbonylation of enynes.The transition-metal-catalyzed cyclocarbonylation of enynes is an attractive research area, in that it provides easy access to the construction of bicyclic cyclopentenone frameworks from open-chain compounds. 1 Because of its synthetic usefulness, considerable efforts have been focused on identifying an easy-to-handle carbonyl source that can be substituted for carbon monoxide in such reactions. Recent studies by us and others have demonstrated that formyl compounds, such as aldehydes 2 and a formate, 3 could be utilized as a carbonyl source using a strategy based on the catalytic decarbonylation of the formyl group. Quite recently, it was found that readily available carbon resources, including aldoses, can be used as a carbonyl source in such reactions. Chung et al. reported on rhodium(I)-catalyzed reactions of an enyne with D-glucose as a carbonyl source. 4 Independently, we reported on the use of aldose derivatives as a carbonyl source in cyclocarbonylation reactions. 5 We next targeted on the use of sugar alcohols or their derivatives as a new carbonyl source in the transformation. Sugar alcohols as well as carbohydrates represent readily available carbon resources that occur widely in nature. Chung's report revealed that xylitol is also applicable as a carbonyl source through a dehydrogenation-decarbonylation sequence of the alcohol moiety in the presence of a catalyst. 4 Herein we report on the highly efficient cyclocarbonylation of enynes using glyceraldehyde acetonide, which is simply prepared from glycerol 6 and D-mannitol, as a carbonyl source. 7Racemic and chiral glyceraldehyde acetonide, rac-and (R)-1, were synthesized in two steps from glycerol 8 and Dmannitol, 9 respectively. We first examined the cyclocarbonylation of enyne 2a with rac-1. Under catalytic conditions consisting of 2.5 mol% of [RhCl(cod)] 2 and 5 mol% of dppp [1,3-bis(diphenylphosphino)propane], the reaction of 2a with two equivalents of rac-1 in toluene at reflux resulted in the complete consumption of 2a in two hours to give the desired product 3a in 82% yield (Scheme 1). Chiral (R)-1 also reacted smoothly to afford the racemic product in high yield, however, the chirality of (R)-1 appeared to have no effect on the enantioselectivity during the synthesis of 3a. As a result, it was found that the multifunctionalized aldehyde 1, which is derived from a sugar alcohol, such as glycerol and D-mannitol, also can be utilized as an effective carbonyl source in the cyclocarbonylation of enynes. 10

The new, efficient, and stereoselective method to prepare biologically important 3‐arylated isoindolinones can also be applied to synthesize enantioenriched 3‐arylphthalides.