Organocatalyzed asymmetric Michael reaction of β-aryl-α-ketophosphonates and nitroalkenes

Abstract

The first enantioselective Michael reaction of β-aryl-α-ketophosphonates and nitroalkenes has been brealized by using a new bifunctional Takemoto-type thiourea catalyst. The primary Michael adducts obtained were converted in situ to the corresponding amides through the aminolysis. High yields, excellent diastereoselectivities (>95:5 dr), and good enantioselectivities (up to 81% ee) have been achieved for the corresponding α ,β-disubstituted γ-nitroamides. This reaction againdemon strated that α-ketophosphonates are interesting pronucleophiles that can be used as amide surrogates in organocatalyzed reactions.

Recent Advances in Asymmetric Organocatalyzed Conjugate Additions to Nitroalkenes

“…A thiourea derived from cyclohexane-1,2-diamine 71 has shown to be an efficient catalyst to carry out the Michael reaction of unusual β-aryl-α-ketophosphonates to nitroalkenes giving products 70 with excellent diastereoselectivities and good enantioselectivities ( Scheme 15 ). In this case, the tertiary amine moiety of catalyst 71 deprotonates the β-aryl-α-ketophosphonate leading to an enolate which is closely associated with the protonated catalyst by ionic and hydrogen bonding interactions [ 97 ].…”

Synthesis and Reactions of α-Hydroxyphosphonates

“…The oxidation of α-hydroxyphosphonates 1B affords the corresponding α-ketophosphonates ( 35 ) that are versatile precursors of a series of organophosphorus compounds [ 100 , 101 , 102 ]. The application of metal compounds with variable valency as the oxidizing agent is predominating in the literature.…”

Enantioselective Synthesis of β-Nitro Phosphonates Catalyzed by a Secondary Amine Bisthiourea

“…The β-nitro functional group can theoretically generate hydrogen bonds with the catalyst to assist the enantioselective Michael addition process. 42 When we mixed the catalyst 3g with [(E)-2nitrovinyl]benzene (1a), both N-hydrogen atoms of the bisthiourea moieties were shifted downfield [Figure 2(D)], clearly indicating an interaction between the nitroalkene and the catalyst. This was confirmed by the observation of a downfield shift of the β-nitrostyrene protons Ha and Hb after interaction with the catalyst [Figure 2(B)], whereas on addition of phosphonate 2a to a mixture of the catalyst and substrate, the H′′ protons shifted upfield, whereas the H′ proton shifted downfield, suggesting that the nucleophile and substrate interacted weakly with catalyst [Figure 2(E)].…”