Asymmetric 1,3‐Dipolar Cycloaddition Reaction between α,β‐Unsaturated Aldehydes and Nitrones Catalyzed by Well‐Defined Iridium or Rhodium Catalysts

Abstract

Reaction of the complexes (SM,RC)‐[(η5‐C5Me5)M{(R)‐Prophos}(H2O)](SbF6)2 (M=Rh, Ir) with α,β‐unsaturated aldehydes diastereoselectively gave complexes (SM,RC)‐[(η5‐C5Me5)M{(R)‐Prophos}(enal)](SbF6)2 which have been fully characterized, including an X‐ray molecular structure determination of the complex (SRh,RC)‐[(η5‐C5Me5)Rh{(R)‐Prophos}(trans‐2‐methyl‐2‐pentenal)](SbF6)2. These enal complexes efficiently catalyze the enantioselective 1,3‐dipolar cycloaddition of the nitrones N‐benzylideneaniline N‐oxide and 3,4‐dihydroisoquinoline N‐oxide to the corresponding enals. Reactions occur with excellent regioselectivity, perfect endo selectivity and with enantiomeric excesses up to 94 %. The absolute configuration of the adduct 5‐methyl‐2,3‐diphenylisoxazolidine‐4‐carboxaldehyde was determined through its (R)‐(−)‐α‐methylbenzylamine derivative.

The Future of Catalysis by Chiral Lewis Acids

“…Enantioselective approaches involving transition metal catalysts have been successful with bidentate dipolarophiles such as those derived from oxazolidinones that provide two-point binding to the chiral Lewis acid [98]. However, there have been few examples of highly selective 1,3-dipolar cycloaddition reactions with α,β-unsaturated aldehydes that are monodentate dipolarophiles [8,[99][100][101][102], and those using methacrolein have shown greater selectivities than those with acrolein. A clear understanding of factors that influence reactivity and selectivity in nitrone cycloaddition reactions has been reported for reactions catalyzed by chiral dirhodium(II,III) carboxamidates (Scheme 20) [103].…”

“…These reactions [Scheme 21] are reported to occur quantitatively with high regioselectivity and stereocontrol [100]. The uses of chiral N,N 0 -dioxides for nitrone cycloaddition to alkylidene malonates [104] and to 3-arylidene-oxindoles [105] have been reported.…”

Metal complexes versus organocatalysts in asymmetric 1,3-dipolar cycloadditions

“…Unlike the last optimised reaction conditions described, the reactions carried out with a,b-unsaturated aldehydes 100 and nitrone 95 were better asymmetrically induced by chiral complex 80 (L = enal ligand), obtaining 3,4-endo-103 cycloadducts in very good yields and moderate to good enantioselections (Scheme 21, reaction c). 52 The chiral environment of complexes 79-83 ( Figure 7) was originated by the coordination with different diphosphanes, but the most synthetically useful complex was obtained when chiral 1,2-(diphenylphosphino) propane (R-Prophos) was employed (complexes 79 and 80). Interestingly, complexes 81-83 gave better results than catalysts 79 and 80 in the 1,3-DC was surveyed with nitrones 92b, and 95 with a variety of dipolarophiles.…”

“…Interestingly, complexes 81-83 gave better results than catalysts 79 and 80 in the 1,3-DC was surveyed with nitrones 92b, and 95 with a variety of dipolarophiles. 52 An efficient regio-, diastereo-, and enantioselective transformation of several nitrones with allylic alcohols promoted by the chiral complex formed by diethylzinc and (R,R)-diisopropyl tartrate (DIPT) was achieved 84 (20 mol%, Figure 7). 53 In several examples, this reaction provided an approach to highly functionalised 3,5-transisoxazolidines with almost complete enantioselectivity (up to 83% yield and up to > 99% ee).…”

Asymmetric Lewis acid-catalyzed 1,3-dipolar cycloadditions

“…A subsequent full study showed the efficiency and versatility of these complexes as catalysts for the reaction of diarylnitrones and α,β-unsaturated aldehydes [7,8]. Carmona's dicationic, half-sandwich, Rh and Ir aqua complexes containing diphosphine or PN ligands also proved good catalysts for this transformation [9][10][11][12]. The same group recently provided the first examples of asymmetric catalytic cycloaddition reactions of nitrones with methacrylonitrile [13].…”