The Cu(I)-catalysed 1,3-dipolar "click" cycloaddition is utilised as an efficient reaction for the preparation of novel fluorene-based conjugated polymers.
Racemic Baylis-Hillman carbonates can be converted in densely functionalized products by reaction with cyano esters in the presence of a catalytic amount of a modified Cinchona alkaloid in high enantioselectivities and fair diastereoselectivi-ties. A rational for the observed stereoselectivity is presented. The enantioselective construction of all-carbon qua-ternary stereocenters still represents a major challenge in synthetic organic chemistry. [1] The simultaneous generation of two adjacent quaternary and terti-ary stereocenters is even more problematic and, to date, only few examples have been reported, all of them relying on conjugate additions. [2] The Morita-Baylis-Hillman (MBH) reaction has attracted the attention of many research groups, due to the possibility of accessing densely functionalized products in one step. [3] In the last decade, these efforts have resulted in great progress being made in terms of rate, scope and enantioselectivity. Upon conversion of the alcohol to a leaving group, MBH adducts become substrates for asymmetric allylic substitution. Trost and co-workers successfully applied this strategy to the synthesis of natural products employing chiral palladium catalysts in the dynamic kinetic resolution of MBH acetates. [4] More recently, other groups investigated the feasibility of this reaction with an (asymmetric) nucleo-philic organocatalyst, [5] relying on a tandem S N 2'/S N 2' substitution sequence (Scheme 1). DABCO [6] and triphenylphosphine [7] were shown to catalyze the allylic substitution of MBH adducts with good regioselectivity. Krische et al. reported that commercially available Cl-OMe-BIPHEP promotes the amination of MBH acetates with phthalimide in 56 % ee. [8] Cinchona derivatives were also employed as catalysts for related transformations: (DHQD) 2 PHAL was used in the asymmetric hydrolysis of MBH acetates with sodium bicarbonate, giving medium to high levels of asymmetric induction (up to 84 % ee). [9] Lu and co-workers investigated the reaction of MBH car-bonates with a variety of nucleophiles in the presence of a catalytic amount of b-isocupreidine (b-ICPD), [10] a strained quinidine derivative that was earlier used by Hatakeyama et al. to achieve excellent levels of enantioselection in the parent MBH reaction of alde-hydes and activated acrylates. [11] Remarkably, besides Scheme 1. Organocatalytic vs. Pd-catalyzed allylic substitution .
Racemic Baylis-Hillman carbonates can be converted in densely functionalized products by reaction with cyano esters in the presence of a catalytic amount of a modified Cinchona alkaloid in high enantioselectivities and fair diastereoselectivities. A rational for the observed stereoselectivity is presented.Keywords: allylic substitution; asymmetric catalysis; Baylis-Hillman reaction; Cinchona alkaloids; hydrogen bondThe enantioselective construction of all-carbon quaternary stereocenters still represents a major challenge in synthetic organic chemistry.[1] The simultaneous generation of two adjacent quaternary and tertiary stereocenters is even more problematic and, to date, only few examples have been reported, all of them relying on conjugate additions.[2]The Morita-Baylis-Hillman (MBH) reaction has attracted the attention of many research groups, due to the possibility of accessing densely functionalized products in one step.[3] In the last decade, these efforts have resulted in great progress being made in terms of rate, scope and enantioselectivity. Upon conversion of the alcohol to a leaving group, MBH adducts become substrates for asymmetric allylic substitution. Trost and co-workers successfully applied this strategy to the synthesis of natural products employing chiral palladium catalysts in the dynamic kinetic resolution of MBH acetates. [4] More recently, other groups investigated the feasibility of this reaction with an (asymmetric) nucleophilic organocatalyst, [5] relying on a tandem S N 2'/S N 2' substitution sequence (Scheme 1). DABCO [6] and triphenylphosphine [7] were shown to catalyze the allylic substitution of MBH adducts with good regioselectivity. Krische et al. reported that commercially available Cl-OMe-BIPHEP promotes the amination of MBH acetates with phthalimide in 56 % ee.[8] Cinchona derivatives were also employed as catalysts for related transformations: (DHQD) 2 PHAL was used in the asymmetric hydrolysis of MBH acetates with sodium bicarbonate, giving medium to high levels of asymmetric induction (up to 84 % ee).[9] Lu and co-workers investigated the reaction of MBH carbonates with a variety of nucleophiles in the presence of a catalytic amount of b-isocupreidine (b-ICPD), [10] a strained quinidine derivative that was earlier used by Hatakeyama et al. to achieve excellent levels of enantioselection in the parent MBH reaction of aldehydes and activated acrylates.[11] Remarkably, besides Scheme 1. Organocatalytic vs. Pd-catalyzed allylic substitution.
Significance: Herein the authors describe a method for the asymmetric allylic alkylation of racemic Morita-Baylis-Hillman (MBH) carbonates (1) derived from aromatic aldehydes. Reaction with cyanoacetates 2 in the presence of 20 mol% of b-isocupreidine (b-ICPD), a strained quinidine derivative, delivers densely functionalized products of the general type 3, featuring two adjacent quaternary and tertiary stereocenters, in good yields with reasonable diastereo-and enantioselectivities. Due to kinetic resolution in the first conjugate addition A, this process also provides access to highly enantioenriched MBH carbonates (see selected example). Based on experimental observations, the authors proposed a mechanism where b-ICPD acts as bifunctional Lewis base/ Brønsted acid catalyst achieving effective face shielding in the second conjugate addition B.Comment: Upon conversion of the alcohol into a leaving group, MBH adducts become substrates for allylic substitution, one example within the great variety of applications of MBH products (D. Basavaiah et al. Chem. Rev. 2003, 103, 811-891). Lu and co-workers investigated a similar reaction with various, mainly O-and N-centered nucleophiles in the presence of b-ICPD (Y. Du et al. Tetrahedron Lett. 2004, 45, 4967-4971). Hiemstra and co-workers now extended this method to the use of cyanoacetates 2 as nucleophiles, resulting in the formation of quaternary stereocenters. Since some products 3 were obtained as crystalline solids, the authors were able to increase the optical purity via recrystallization up to er = 99:1. However, improvement of the observed diastereoand enantioselectivites through further catalyst optimization might be desirable. R 1 CO 2 Me OBoc CN EtO 2 C R 2 R 1 CO 2 Me EtO 2 C CN R 2 * * β-ICPD (20 mol%) toluene, -20 °C or 0 °C, 24-96 h 12 3 R 1 = Ph, 4-NO 2 C 6 H 4 , 3-ClC 6 H 4 , 3-BrC 6 H 4 , 2-MeC 6 H 4 , 1-Naph R 2 = Ph, Me 6 examples 66-95% yield dr = 1:1 to 4:1 er = 58:42 to 92.5:7.5 (2 equiv) N N OH O β-ICPD Selected example: R 1 CO 2 Me OBoc R 1 OBoc O OMe R 1 O OMe R 1 Nu O OMe * R 1 CO 2 Me Nu * CO 2 β-ICPD A 95% yield dr = 3:1 er = 90:10 CO 2 Me Ph CO 2 Et CN Br (R) er = 95:5 CO 2 Me OBoc Br (S) Proposed mechanism: t-BuOt-BuOH
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