Recent Advances in Organocatalytic Asymmetric Morita–Baylis–Hillman/aza-Morita–Baylis–Hillman Reactions

Efficient Synthesis of Cyclopropane‐Fused Heterocycles with Bromoethylsulfonium Salt

“…The methodology readily lends itself to asymmetric synthesis, since the aza-Morita-Baylis-Hillman adducts 7a, 7b are obtainable using asymmetric organocatalysis. [31] This was illustrated in the use of (+)-7a (82% ee), which gave the [3.1.0] bicycle (+)-8a without measurable racemization, which was increased to >99% ee after recrystallization. Table 2: Reactivity of (aza)-Morita-Baylis-Hillman adducts.…”

Total Synthesis of Biologically Active Natural Products Based on Highly Selective Synthetic Methodologies

“…However, the major problems associated with this reaction are its slow reaction rate and difficulty in achieving a high level of asymmetric induction. [1][2][3][4][5][6] 2.1.1 Development of the β-Isocupreidine-Hexafluoroisopropyl Acrylate Method [7][8][9] In 1999, we achieved the first breakthrough in the catalytic asymmetric MBH reaction employing β-isocupreidine (β-ICD) as a chiral bifunctional catalyst and 1,1,1,3,3,3-hexafluoroisopropyl acrylate (HFIPA) as an activated alkene (β-ICD-HFIPA method) 7) (Chart 2). The reactions were carried out using 0.1 eq.…”

“…After our discovery of this β-ICD-HFIPA method, a number of sophisticated catalytic systems were developed. [1][2][3][4][5][6] This β-ICD-HFIPA method is applicable to chiral α-amino aldehydes 7 that afford the synthetically useful α-methylene-β-hydroxy-γ-amino acid esters 8 11) (Chart 4). It was found that β-ICD-catalyzed reactions of N-Boc-α-amino aldehydes 7 with HFIPA proceeded without racemization to give enantiomerically pure esters 8 and exhibited a marked match-mismatch relationship.…”

P-C bond formation in reactions of Morita-Baylis-Hillman adducts with phosphorus nucleophiles

“…In addition, owing to the nascent chiral center, enantiomerically enriched compounds can be obtained from prochiral electrophiles. 7 The stereoselectivity can be induced by chiral substrates, catalysts or the reaction environment. The ultimate benefit is the synthetic feasibility of the products, the Morita-Baylis-Hillman adducts.…”

“…8 The predominating preparative utility of the MBH adducts originates from the susceptibility of the allylic / α,β-unsaturated system to nucleophilic substitution and addition. [3][4][5][6][7][8] The mechanism and the position of the displacements strongly depend on the structure of the substrates and the manipulation conditions (Scheme 2). Attack on the primary MBH adducts, allyl alcohols, typically proceeds according to a mechanism of Michaeltype addition of a nucleophile to the electrophilic terminal carbon of an activated unsaturated system (Scheme 2A).…”