Chiral Ruthenium Lewis Acid Catalyzed Intramolecular Diels−Alder Reactions

Abstract

Single point binding ruthenium Lewis acid catalysts [Ru(acetone)(S,S)-BIPHOP-F)Cp][SbF(6)] ((S,S)-1b) and [Ru(acetone)(S,S)-BIPHOP-F)(indenyl)][SbF(6)] ((S,S)-1c) efficiently catalyze intramolecular Diels-Alder (IMDA) reactions under mild conditions to afford the endo cycloaddition products as the major product in excellent yields with high diastereo- and enantioselectivities.

Intramolecular Diels–Alder reactions using chiral ruthenium Lewis acids and application in the total synthesis of ent-ledol

“…2d The higher enantioselectivity may result from a more restricted space in the reaction site in the indenyl catalyst when compared to the Cp catalyst. 2b, 22 As detailed in the preliminary communication of this paper, the absolute configuration of 27 was ascertained by an X-ray structure determination after derivatization. Triene 9, previously investigated in the asymmetric IMDA reaction with a chiral acyloxy borane catalyst, 26c was prepared and used in IMDA reactions with chiral Ru catalysts 1a and 1b (Table 3).…”

“…The absolute configurations of 28-30 were assigned based on direct comparison of their CD spectra with that of the hydrazone derivative of adduct 27 after transforming to their corresponding hydrazone compounds. 22…”

“…We next probed type 1 IMDA reactions. 22 Triene 4 23 was unreactive, and coordination to 1a does not appear to occur as evidenced by the lack of change in the 1 H-NMR spectrum when mixing trienone 4 with an equimolar quantity of complex 1a. Ketone 4 may be too bulky to fit into the Lewis acidic site.…”

“…MgSO 4 ) and concentrated in vacuo. General experimental procedure for IMDA of trienal 7, 9, 10 and 11 22 In a 50 mL oven-dried Schlenk tube equipped with a magnetic stirring bar at r.t. and under N 2 , Ru catalyst (70 mg, 0.05 mmol, 0.05 eq) was dissolved in dry CH 2 Cl 2 (1.80 mL). To the stirred mixture, 2,6-lutidine (2.3 mL, 0.02 mmol, 0.02 eq) and a solution of triene (1.00 mmol, 1 eq) in dry CH 2 Cl 2 (1.50 mL) was carefully added, and the resulting solution was stirred at r.t. under N 2 .…”

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.…”