Anti-Selective Asymmetric Nitro-Michael Reaction of Furanones: Diastereocontrol by Catalyst

Abstract

Catalyst-controlled switching of diastereoselectivity from high syn-selectivity (>98/2 dr, syn) to anti-selectivity (up to 96/4 dr, anti) of the asymmetric nitro-Michael reaction of furanones is described. Anti-diastereoselectivity of the nitro-Michael reaction is very rare. With 0.1-5 mol % loadings of an epi-quinine catalyst, the reaction of 5-substituted 2(3H)-furanones with nitroalkenes smoothly proceeded to give the anti-Michael adducts in good yields (up to 95%) with excellent diastereo- and enantioselectivities (up to 96/4 dr, anti; up to 99% ee). DFT calculations support a model that accounts the high anti-diastereoselectivity.

Probing α‐Amino Aldehydes as Weakly Acidic Pronucleophiles: Direct Access to Quaternary α‐Amino Aldehydes by an Enantioselective Michael Addition Catalyzed by Brønsted Bases

“…The reaction proceeded with modest conversion and was accompanied by a small amount of cyclized product 16 a , which resulted from three consecutive Michael–Michael–Henry reactions [23] . Hünig's base (Table 1, entry 2) was less effective than that of Et 3 N and stronger bases, such as the amidine base DBU and guanidines such as MTBD and TBD (Table 1, entries 3 and 4), led to polymerization of the nitroolefin to a great extent, [24] and no adducts derived from 1 A were observed. The conversion into 9 Aa could be increased (Table 1, entries 5 and 6) in the presence of either thiourea or squaramide hydrogen‐bond donors, but no increase in diastereoselectivity nor in the production of cyclized product 16 a was observed.…”

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

“…Capitalizing on these results, the same group turned attention toward the more challenging anti -selective nitro-Michael reaction (Table , entry 3). , Remarkably, the requested catalyst-controlled switching of diastereoselectivity was achieved with the use of bulky 6′-OH- epi -quinine catalyst C30 , that, mirroring the high catalytic activity of C9 in the previous reaction, promoted the addition between diverse sets of deconjugated lactones and nitroolefins, to access anti -configured Michael adducts in good yields (up to 95%) with excellent diastereo- and enantioselectivities (up to 32:1 dr and up to 99% ee).…”

Diastereoselective Organocatalytic Addition of α-Angelica Lactone to β-Halo-α-ketoesters

“…Intriguingly, in all cases we studied, capture of the electrophile at the α-position of the lactone was the dominant mode of reactivity. We speculate that this divergence may arise from the more demanding steric environment imposed by the α-ketoester, as compared with those used in previous reports. − Additionally, for the most part, substitution at the β-position of the α-ketoesters does not affect the intrinsically high diastereoselectivity of the reaction. Using β-halo-β-benzyl α-ketoesters, catalyzed addition of α-angelica lactone provided the aldol products 3a – 3c in modest yields in >20:1 dr (Scheme ).…”

“…This class of nucleophile has been studied in the stereoselective addition to nitrostyrenes and other prochiral electrophiles using cinchona alkaloid-derived thiourea organocatalysts (Scheme b) . Other additions to nitrostyrenes, aldimines, enones, enals, and vinyl sulfones have also been studied. In all of these cases, the α-angelica lactone exhibited electrophilic trapping at the γ-carbon.…”