Synthesis最新文献

This article presents an efficient one-step synthesis of tetrahydropyrazolo[1,5-a]pyrimidines through the recyclization of N-arylitaconimides with aminopyrazoles. The heterocyclic system of pyrazolo[3,4-b]pyrimidine is known for its diverse biological properties, making its derivatives significant in pharmaceutical and medicinal chemistry. The study focuses on the regio- and chemoselective cascade reaction of N-arylitaconimides with 5-aminopyrazoles, demonstrating a new approach to synthesizing pyrazolo[1,5-a]pyrimidines and pyrazolo[3,4-b]pyridines. The methodology, involving boiling in isopropyl alcohol with acetic acid, yields selectively either pyrazolo[3,4-b]pyridines or pyrazolo[1,5-a]pyrimidines based on the substituents in the aminopyrazoles. The study elucidates the reaction mechanism, structural characterization using NMR spectroscopy, and confirms the structures via high-performance liquid chromatography and mass spectrometry. The simplicity and synthetic potential of this approach make it a valuable method for the preparation of these heterocyclic frameworks.

This review highlights the use of DACH as a versatile ligand in catalytic asymmetric transformations providing mechanistic rationales and relevant comments presented in chronological order for each of the 21 reaction types with references up to December 25, 2023. Intended to be as practically comprehensive as possible, this review assembles useful examples of using DACH as a ligand in organocatalytic or as metal complexes in asymmetric transformations. The resulting enantiomerically enriched, if not pure, chiral non-racemic small molecules are of great utility as value added intermediates in the total synthesis of natural products, in the design and synthesis of medicinally important compounds, and in other areas in organic and bioorganic chemistry where chirality plays a role. The graphic image depicts Spartacus with his arms folded in the same sense of chirality as (R,R)-DACH.

1 Introduction

2 DACH: A Brief Historical Narrative

3 Catalytic Asymmetric Hydrogenation of Alkenes

4 Catalytic Asymmetric Dihydroxylation of Alkenes

5 Catalytic Asymmetric Sulfoxidation and Sulfimidation

6 Catalytic Asymmetric 1,4-Conjugate Addition

6.1 Using Jacobsen’s DACH Metal–salen Complexes as Catalysts

6.2 Using Takemoto’s Bifunctional H-Bonding DACH Thiourea Organocatalyst

6.3 Using DACH Ni(II) Complexes as Catalysts

6.4 Using DACH H-Bonding Catalysis

7 Catalytic Asymmetric Epoxidation of Alkenes

8 Catalytic Asymmetric Claisen Rearrangement

9 Catalytic Asymmetric 1,2-Nucleophilic Addition to Carbonyl Compounds

9.1 Catalytic Asymmetric Addition of Dialkylzinc to Aldehydes and Ketones

9.2 Catalytic Asymmetric Alkynylation of Aldehydes and Ketones

9.3 Catalytic Asymmetric Addition of Cyanide to Aldehydes and Ketones

10 Catalytic Asymmetric Allylic Alkylation

11 Catalytic Asymmetric Cyclopropanation of Alkenes

12 Catalytic Asymmetric Cycloaddition Reactions

13 Catalytic Asymmetric Aziridination of Alkenes

14 Catalytic Asymmetric Hydrogenation of Prochiral Ketones and Imines

15 Catalytic Asymmetric Aldol Reactions

16 Catalytic Asymmetric Opening of Small Ring Systems

16.1 Desymmetrization of meso-Epoxides and meso-Aziridines

16.2 Kinetic Resolution of Racemic Epoxides

16.3 Enantioselective Addition of CO₂ to Epoxides

16.4 Enantioselective Ring Opening of Oxetanes

17 Catalytic Asymmetric Strecker Reactions

18 Catalytic Asymmetric Mannich Reactions

19 Catalytic Asymmetric Henry and Aza-Henry Reactions

20 Catalytic Asymmetric Morita–Baylis–Hillman and Rauhut–Currier Reactions

21 Catalytic Asymmetric Petasis Reactions

22 Organocatalytic Asymmetric Cascade Reactions

23 Miscellaneous Catalytic Reactions

24 Conclusion and Outlook

25 DACH Catalysts and Ligands List

The trifluoromethylthio (SCF₃) and trifluoromethylselanyl (SeCF₃) groups possess high electron-withdrawing ability, excellent lipophilicity, good stability, and bioavailability, and they are promising structural motifs in drug design and development. Photoredox catalysis has clear benefits; it is a mild and sustainable methodology for the modification of chemical structures that enables a variety of chemical reactions that are unattainable using classical ionic chemistry. This review focuses on light-initiated trifluoromethylthiolation and trifluoromethylselenolation reactions with diverse SCF₃ and SeCF₃ reagents. Representative transformations either using photocatalysts or through EDA complexes, as well as possible reaction mechanisms, are all discussed in this article.

1 Introduction

2 Photocatalyzed Trifluoromethylthiolation

2.1 Photocatalyzed Trifluoromethylthiolation with MSCF₃ (M = H, [Me₄N], Ag)

2.2 Photocatalyzed Trifluoromethylthiolation with XSCF₃ (X = Cl, CF₃S)

2.3 Photocatalyzed Trifluoromethylthiolation with ArSO₂SCF₃

2.4 Photocatalyzed Trifluoromethylthiolation with N–SCF₃ Reagents

2.5 Photocatalyzed Trifluoromethylthiolation with Other Reagents

3 Photocatalyzed Trifluoromethylselenolation

3.1 Photocatalyzed Trifluoromethylselenolation with [Me₄N][SeCF₃]

3.2 Photocatalyzed Trifluoromethylselenolation with ArSO₂SeCF₃

4 Summary

A simple and efficient approach for the synthesis of privileged oxime esters by employing donor-acceptor cyclopropane diesters (DACs) as one of the potential precursors is reported. The strategy involves Lewis acid catalyzed ring-opening of DACs, resulting in an open-chain intermediate followed by the base-mediated construction of the corresponding oxime esters in a one-pot reaction. Moreover, the process also features the synthesis of diethyl 4-(4-methoxyphenyl)azete-2,2(3H)-dicarboxylate.

The sulfinyl group, as one of the bioisosteres of carbonyl groups, attracts considerable attention in the field of synthetic chemistry. In particular, the asymmetric construction of chiral sulfinyl compounds and their derivatives remains in the early stages of development. Sulfinyl compounds mainly include sulfoxides, sulfinate esters and sulfinamides, according to the different functional groups connected to the sulfur atom. This Review summarizes the fascinating recent progress made over the past decade on the asymmetric synthesis of enantiopure sulfinyl derivatives.

1 Introduction

2 Asymmetric Synthesis of Chiral Sulfoxides

3 Asymmetric Synthesis of Chiral Sulfinate Esters

4 Asymmetric Synthesis of Chiral Sulfinamides

5 Conclusion and Outlook

Based on the parsley seed main component, apiol, efficient approach to polymethoxyquinone C₃- and C₄-acids was developed. The key step of this approach is Baeyer–Villiger rearrangement of carbonyl-substituted polyalkoxybenzenes derived from parsley seed extracts. These acids are the MeO-analogues of natural antioxidants – metabolites of ubiquinone and idebenone. Due to antioxidant properties, they are the potential therapeutic candidates for the treatment of mitochondrial dysfunction.

An improved practical and efficient procedure for the synthesis of non-racemic unnatural α-amino acids through a stereocontrolled rearrangement is reported. Carboxylic acids are converted into azanyl esters RCO₂NHBoc followed by an iron-catalyzed 1,3-nitrogen migration to provide non-racemic α-amino acids in an asymmetric (α-monosubstituted α-amino acids) or enantioconvergent fashion (α,α-disubstituted α-amino acids). Under optimized conditions using a fluorinated chiral iron catalyst and 2,2,6,6-tetramethylpiperidine as the base in a solvent mixture of 1,2-dichlorobenzene and CHCl₃, enantioselectivities of up to 98% ee were obtained. Such high ee values are important for practical purposes, allowing the direct use of many of the obtained N-Boc-protected α-amino acids for subsequent applications.

Oxetanes, 4-membered oxygen-containing heterocycles, were identified to have pharmaceutical applications after the discovery of the chemotherapeutic drug taxol (Paclitaxel) and its analogues. Furthermore, oxetanes have been identified as bioisosteres for several common functional groups and are present in a number of natural products. However, oxetanes are one of the least common oxygen-containing heterocycles in active pharmaceutical ingredients on the market, which can be attributed, in part, due to challenges with their synthesis. Previous strategies rely on nucleophilic substitutions or [2+2]-cycloadditions, but are limited by the stepwise buildup of starting material and limitations in scope resulting from requirements for activated substrates. To address these limitations, we envisioned activating simple carbonyls to their corresponding α-oxy iodides to promote ketyl radical formation. These radicals can then undergo atom-transfer radical addition with alkenes followed by one-pot nucleophilic substitution to produce oxetanes. Herein, we present a proof-of-principle of this strategy in which fluoroalkyl carbonyls are successfully converted into the corresponding fluoroalkyl oxetanes.

A wide range of α-aryl-α-diazophosphonates were easily prepared via modified diazo transfer reaction. Benzylphoshonates reacted with tosyl azide (TsN₃) in the presence of potassium tert-butoxide (KOtBu) to afford diazophosphonates in yields up to 93% (generally 70–80%). Aryldiazophosponates were successfully explored for the synthesis of 5-aryl-substituted pyrazol-3-carboxylates in one pot by the 1,3-dipolar cycloaddition with alkyl acrylates followed by NaH treatment. The second stage led to elimination of the diethoxylphosphoryl moiety with the aromatization of cycle.

Breaking aromaticity by inserting additional atoms within the skeleton of heteroaromatic rings has gained significant attention over the years. As part of the emerging concept of ‘skeletal editing’, this short review retraces the recent progress made on dearomative enlargement reactions of both five- and six-membered heterocycles.

1 Introduction

2 Dearomative Enlargement of Five-Membered Rings

2.1 Pyrroles, Furans, Thiophenes and Their Fused Analogues

2.2 Pyrazoles, Isoxazoles, Isothiazoles and Their Fused Analogues

3 Dearomative Enlargement of Six-Membered Rings

4 Conclusion and Perspectives