Synthesis of Chiral Tetrasubstituted Alkenes by an Asymmetric Cascade Reaction Catalyzed Cooperatively by Cationic Rhodium(I) and Silver(I) Complexes

Abstract

Fantastic four: Tetrasubstituted alkenes have been prepared with high enantioselectivity by the title transformation. This reaction was successfully applied to the enantio‐ and diastereoselective synthesis of tetrasubstituted helical alkenes possessing both central and helical chirality (see scheme).

Rhodium-Catalyzed Annulation Reactions of 2-Alkynylbenzaldehydes and 2-Vinylbenzaldehyde with Unsaturated Compounds

“…Many successful examples have been reported of the former rhodium catalyzed annulation reactions initiated by aldehyde C H bond activation, 2, 6 10,24,26,28,30 while only a few examples have been reported for the latter rhodium catalyzed annulation initiated by alkyne triple bond activation. 22,32 It is worthy of note that the present novel asymmetric annulation reaction described in section 5 32 utilized the multifunctional character of the cationic rhodium(I) catalyst, which enabled the π bond activation, C H bond activation, and metallacycle formation sequence, 35 although assistance of the silver(I) catalyst was necessary. Future work will focus on further utilization of the multifunctional character of the cationic rhodium(I) catalyst for the development of novel organic reactions using functionalized benzaldehyde derivatives.…”

“…24 Interestingly, when the reaction of 2 cyclohex 1 enylethynylbenzaldehyde and N methylisatin was conducted at room temperature in the presence of the cationic rhodium(I)/ Walphos (R,R) 2 catalyst, the unexpected benzopyranone 7a, possessing a tetrasubstituted alkene moiety, was obtained along with the expected spirocyclic benzopyranone 6a (Scheme 16). 32 Screening of chiral ligands revealed that the use of Walphos (R,R) 8 furnishes 7a in almost quantitative yield and high enantiomeric excess (Scheme 16). However the reactions of 2 alkynylbenzaldehydes possessing an alkyl, isoprope- nyl, or aryl group at the alkyne terminus with N methylisatin in the presence of the cationic rhodium(I)/(R,R) 2 or (R,R) 8 catalyst furnished spirocyclic benzopyranones as the sole products.…”

“…33 As the π electrophilicity of the cationic rhodium(I) complex might not be strong enough to promote the formation of ketoaldehyde 9b (R n Bu in Scheme 17) via benzopyrilium intermediate D (R n Bu in Scheme 17), the reaction of 2 hexynylbenzaldehyde with N methylisatin was investigated in the presence of the cationic rhodium(I)/(R,R) 8 complex (5 mol %) and an additional, strongly π electrophilic transition metal complex (10 mol %). Among the additives examined (Table 8, entries 1 4), 32 AgBF 4 showed the highest selectivity for formation of tetrasubstituted alkene 7b (entry 4), although the yield of 7b was extremely low. We observed that the brownish CH 2 Cl 2 solution of the cationic rhodium(I)/ (R,R) 8 complex becomes green on addition of AgBF 4 .…”

“…32 Alkyl (entries 1 3), alkenyl (entry 4), and aryl substituted 2 alkynylbenzaldehydes (entries 5 and 6) could participate in this reaction. With respect to the cyclic dicarbonyl component, not only N methylisatin (entries 1 6) but also N phenylisatin (entry 7), NH isatin (entry 8), and acenaphthenequinone (entries 9 and 10) could be employed.…”

“…32 1 Alkynyl 2 naphthaldehydes reacted with N methylisatin to afford the corresponding helical alkenes as a single diastereomer in good yields with high enantiomeric excess (entries 1 4). Although low enantioselectivities were observed in the syntheses of more sterically demanding helical alkenes (entries 5 and 6), the enantiomeric purity of the products could be readily improved by a single recrystallization (entry 5).…”