Ruthenium–Lewis Acid Catalyzed Asymmetric Diels–Alder Reactions between Dienes and α,β‐Unsaturated Ketones

Abstract

The complex [Ru(Cp)(R,R-BIPHOP-F)(acetone)][SbF(6)], (R,R)-1 a, was used as catalyst for asymmetric Diels-Alder reactions between dienes (cyclopentadiene, methylcyclopentadiene, isoprene, 2,3-dimethylbutadiene) and alpha,beta-unsaturated ketones (methyl vinyl ketone (MVK), ethyl vinyl ketone, divinyl ketone, alpha-bromovinyl methyl ketone and alpha-chlorovinyl methyl ketone). The cycloaddition products were obtained in yields of 50-90 % and with enantioselectivities up to 96 % ee. Ethyl vinyl ketone, divinyl ketone and the halogenated vinyl ketones worked best and their reactions with acyclic dienes consistently provided products with >90 % ee. alpha-Chlorovinyl methyl ketone performed better than alpha-bromovinyl methyl ketone. The reaction also provided a [4.3.1]bicyclic ring system in 95 % ee through an intramolecular cycloaddition reaction. Crystal structure determinations of [Ru(Cp)((S,S)-BIPHOP-F)(mvk)][SbF(6)], (S,S)-1 b, and [Ru(Cp)((R,R)-Me(4)BIPHOP-F)(acrolein)][SbF(6)], (R,R)-2 b, provided the basis for a rationalization of the asymmetric induction.

Reactions of Trienals Catalyzed by Chiral Ruthenium Lewis Acids

“…The study involved trienes 2 (Scheme 5) and 3-7 (Scheme 6) and the results of IMDA reactions of these substrates catalyzed by (S,S)-1a and 1b were investigated. [3,7,8] Triene 2 containing a vinyl ketone dieneophile, provided the highly enantiomerically enriched bridgehead adduct 8 in good yield. [3] Reflecting the lower reactivity of b-substituted keto-dienophiles, triene 5 failed to react.…”

“…[3,7,8] Triene 2 containing a vinyl ketone dieneophile, provided the highly enantiomerically enriched bridgehead adduct 8 in good yield. [3] Reflecting the lower reactivity of b-substituted keto-dienophiles, triene 5 failed to react. Trienals 3 [9a,b] and 4, [9c] which were previously used in asymmetric IMDA reaction by Yamamoto, furnished the cycloadducts 9 and 10, respectively in good yields with high enantioselectivities.…”

“…Significant to the success was the hydride-labilizing effect, which enabled CO substitution in the in situ formed [RuCp(CO) 2 These mild chiral Lewis acids proved to be excellent catalysts for intermolecular Diels-Alder (DA) reactions of various dienes with enals [2] and enones, [3] 1,3-dipolar cycloadditions of enals with nitrones [4] and of enals with nitrile oxides [4b,5] as shown in Scheme 3. The 1,4-addition of thiophenols to enones could also be carried out using these catalysts.…”

“…[3] To extend the application, we probed the potential of (S,S)-1a and 1b in the intramolecular Diels-Alder (IMDA) reaction. The study involved trienes 2 (Scheme 5) and 3-7 (Scheme 6) and the results of IMDA reactions of these substrates catalyzed by (S,S)-1a and 1b were investigated.…”

“…[2][3][4][5][6] For the IMDA reaction involving triene 3 the diene approach leading to the observed endo product 9 was modeled as shown in Fig. 2.…”