Catalytic Asymmetric Formation of δ‐Lactones from Unsaturated Acyl Halides

Abstract

Previously unexplored enantiopure zwitterionic ammonium dienolates have been utilized in this work as reactive intermediates that act as diene components in hetero-Diels-Alder reactions (HDAs) with aldehydes to produce optically active delta-lactones, subunits of numerous bioactive products. The dienolates were generated in situ from E/Z mixtures of alpha,beta-unsaturated acid chlorides by use of a nucleophilic quinidine derivative and Sn(OTf)(2) as co-catalyst. The latter component was not directly involved in the cycloaddition step with aldehydes and simply facilitated the formation of the reactive dienolate species. The scope of the cycloaddition was considerably improved by use of a complex formed from Er(OTf)(3) and a simple commercially available norephedrine-derived ligand that tolerated a broad range of aromatic and heteroaromatic aldehydes for a cooperative bifunctional Lewis-acid-/Lewis-base-catalyzed reaction, providing alpha,beta-unsaturated delta-lactones with excellent enantioselectivities. Mechanistic studies confirmed the formation of the dienolate intermediates for both catalytic systems. The active Er(III) complex is most likely a monomeric species. Interestingly, all lanthanides can catalyze the title reaction, but the efficiency in terms of yield and enantioselectivity depends directly on the radius of the Ln(III) ion. Similarly, use of the pseudolanthanides Sc(III) and Y(III) also resulted in product formation, whereas the larger La(III) and other transition metal salts, as well as main group metal salts, proved to be inefficient. In addition, various synthetic transformations of 6-CCl(3)- or 4-silyl-substituted alpha,beta-unsaturated delta-lactones, giving access to a number of valuable delta-lactone building blocks, were investigated.

Lewis Acid/Base Catalyzed [2+2]‐Cycloaddition of Sulfenes and Aldehydes: A Versatile Entry to Chiral Sulfonyl and Sulfinyl Derivatives

“…The best yield (41 %) and enantioselectivity (ee = 51 %) was found with diydroquinine 2,5-diphenyl-4,6-pyrimidinediyl diether ((DHQ) 2 PYR; [24] Table 4, entry 6). [25] A screening of various Lewis acids (entries [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] in the presence of this chiral nucleophile revealed that most metal triflate salts, for example, those of Li…”

Cycloaddition and Electrocyclic Reactions of Vinylketenes, Allenylketenes, and Alkynylketenes

“…The corresponding reaction with benzaldehyde requires a different chiral catalyst for optimal results (Scheme 143). 156 …”

“…Vinylketenes, generated in situ by dehydrochlorination, react with trichloroacetaldehyde in the presence of Sn(OTf) 2 and O-trimethylsilylquinidine as a chiral catalyst to afford δ-lactones such as 123 in good yields and with high enantiomeric purity (Scheme 142). 156,157,32 Reaction in the presence of MeOD provides the methyl ester with partial deuterium incorporation. This result is interpreted as showing the involvement of both a vinylketene intermediate and a route that involves displacement of chloride by the amine catalyst followed by deprotonation to afford a dienolate intermediate, which leads to lactone products without a vinylketene intermediate.…”

Enantioselective Vinylogous Organocascade Reactions

“…If this electrophile is tethered to a masked nucleophile, a cascade reaction occurs where the nucleophilic moiety utilizes the intrinsic nature of the NHC as a leaving group to attack the carbonyl moiety and undergo a cyclization (En 2 ‐S) (Figure ). These En 2 ‐S cascade reactions rely on the NHC catalyst for both new bond‐forming steps, and although a cycloaddition pathway cannot be excluded for these types of transformations, the current understanding is that they are more likely to proceed through a cascade process 45…”