HDA Reaction Research Articles

Highly Enantio- and Diastereoselective Brassard Type Hetero-Diels−Alder Approach to 5-Methyl-Containing α,β-Unsaturated δ-Lactones

Two efficient new chiral copper (II) Schiff base complexes were developed for the highly enantio- and diastereoselective HDA reaction of Brassard type diene 1b with aldehydes, to afford the corresponding 5-methyl-containing alpha,beta-unsaturated delta-lactone derivatives in moderate yields, high enantioselectivities (up to 99% ee) and excellent diastereoselectivities (up to 99:1 anti/syn). On the basis of the absolute configuration of 4a-4j disclosed by X-ray diffraction and CD analysis, a possible transition-state model for the enantio- and diastereoselective catalytic reaction has been proposed.

One catalyst for two distinct reactions: sequential asymmetric hetero Diels–Alder reaction and diethylzinc addition

This paper describes the successful development of a series of chiral zinc catalysts containing ( R)-3,3′-Br 2-BINOL ligand and various diimine activators for enantioselective HDA reaction of Danishefsky's diene with aldehydes through a combinatorial approach, affording the corresponding 2,3-dihydro-4 H-pyran-4-one derivatives in excellent yields and enantioselectivities. The application of this type of catalysts was also extended to the diethylzinc addition to the benzaldehyde, affording the corresponding secondary alcohol with up to 94.5% ee under optimized conditions. On the basis of these facts, the integration of two distinct enantioselective reactions, HDA and diethylzinc addition reactions, has been realized in one-pot with the promotion of a single chiral zinc catalyst in a sequential manner. The impact of diimine additive on the catalytic system of HDA reaction was also investigated by probing the nonlinear effect of reaction system. The positive nonlinear effect exhibited in the catalytic system could be attributed to the poor solubility of the heterochiral zinc species. On the basis of various experimental findings disclosed in this research, a possible mechanism for the asymmetric induction in the 3,3′-Br 2-BINOL/Zn/diimine catalyzed enantioselective HDA reaction of Danishefsky's diene with aldehydes was outlined.

Catalytic Asymmetric Synthesis of a Potent Thiomarinol Antibiotic.

Thiomarinols, isolated from the bacterium Alteromonas rava sp. nov. SANK 73390, are potent marine antibiotics that possess both Gram-positive and Gram-negative activity. The first total synthesis of a member of the thiomarinol class of marine antibiotics was achieved in a remarkable global yield of 22% (from 3-boronoacrolein pinacolate). The highlight of this synthesis is the efficient catalytic enantio-, regio-, E/Z-, and diastereoselective three-component inverse electron demand Diels-Alder/allylboration sequence. This key operation provides a rare example of an enantioselective HDA reaction involving acyclic 2-substituted enol ethers, and it featured an unusual but fortuitous kinetic selection that favored the requisite Z-dienophile.

Steady-State Process Optimization with Guaranteed Robust Stability and Flexibility: Application to HDA Reaction Section

This paper extends a recently suggested approach for the steady-state process optimization with guaranteed robust stability and flexibility under parametric uncertainty. The approach is based on measuring the distance of a candidate point of operation to so-called critical manifolds. Critical manifolds locally separate regions of the space of the process and controller design parameters with desired process traits from those regions with undesired traits. Pairs of desired and undesired traits may, for example, be feasibility and infeasibility of operation, stability and instability, or more generally, desired dynamical behavior and undesired dynamical behavior. While in previous applications knowledge on the existence and location of critical manifolds were assumed to be available before the optimization was attempted, the present paper presents an algorithm in which critical manifolds are automatically detected as the optimization proceeds. This algorithm, which is the conceptual contribution of the paper, allows the application of the critical manifold-based approach to processes for which no a priori information on the existence and location of critical manifolds exists. As a proof of concept the algorithm is applied to the reaction section of the HDA process. An analysis of the critical manifolds of this process model is not available. Since 12 uncertain parameters exists, analyzing the critical manifolds would be tedious. While an analysis of the 12 uncertain parameters is not practical, the critical manifold-based optimization approach can be applied to models with this number of parameters and beyond.

Catalytic Asymmetric Synthesis of a Potent Thiomarinol Antibiotic

Thiomarinols, isolated from the bacterium Alteromonas rava sp. nov. SANK 73390, are potent marine antibiotics that possess both Gram-positive and Gram-negative activity. The first total synthesis of a member of the thiomarinol class of marine antibiotics was achieved in a remarkable global yield of 22% (from 3-boronoacrolein pinacolate). The highlight of this synthesis is the efficient catalytic enantio-, regio-, E/Z-, and diastereoselective three-component inverse electron demand Diels-Alder/allylboration sequence. This key operation provides a rare example of an enantioselective HDA reaction involving acyclic 2-substituted enol ethers, and it featured an unusual but fortuitous kinetic selection that favored the requisite Z-dienophile.

Stereoselective Synthesis of New Higher Carbon Sugars from D‐Xylose

AbstractA simple, one‐pot multi‐step route for the synthesis of a higher carbon sugar 3 by the HDA reaction of a α,β‐unsaturated ketone prepared in situ from protected D‐xylose with PDC in C6H6 or CH3CN, followed by the reduction to the C10 higher carbon sugar derivatives 4 and 5, is described. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Synthesis of Dendritic Schiff Base Ligands for Titanium Catalyzed Enantioselective HDA Reaction of Danishelfsky's Diene with Aldehydes

AbstractA new type of dendritic NOBIN derived Schiff base ligands has been synthesized and applied to titanium catalyzed hetero‐Diels‐Alder reaction of Danishelfsky's diene and aldehydes, affording the corresponding 2‐substituted 2,3‐dihydro‐4H‐pyran‐4‐one in good yields and moderate enantioselectivities (up to 59.2% ee). It was found that the size of dendron attached to the tri‐dentated ligands has slight impact on the enantioselectivity of the reaction and the second generation of dendritic ligand exhibited the best enantioselectivity.

Dramatically synergetic effect of carboxylic acid additive on tridentate titanium catalyzed enantioselective hetero-diels-alder reaction: additive acceleration and nonlinear effect.

This paper describes the successful development of a group of highly efficient chiral tridentate titanium catalysts for hetero-Diels-Alder reaction of Danishefsky's diene and a variety of aldehydes through ligand and additive diversity. Dramatically synergetic effect of carboxylic acid additives and influence of substituent in chiral Schiff base ligands on the enantioselectivities of the reaction are reported. It was found that a chiral drug Naproxen (A21) was a highly efficient additive for Ti-catalyzed HDA reaction, affording 2-substituted 2,3-dihydro-4H-pyran-4-one in up to 97 % ee and >99 % yields. Quantitative study of the effect of chiral carboxylic acid A21 revealed that the reaction could be accelerated by one order of magnitude. Another interesting feature of present catalytic system is the existence of significant positive nonlinear effect, which indicates that the heterochiral Schiff base-titanium complexes may have higher stability than their homochiral counterparts. As a result, the homochiral Schiff base-titanium complexes with higher ee than that of starting ligand will react with carboxylic acid additive to form the more active species and predominate the catalytic process. The isolation and characterization of stable heterochiral ((+/-)-L1)2Ti complex has also been successful, which strongly supported the explanation for positive nonlinear effect observed in the catalytic system.