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The Journal of Organic Chemistry Oct 2018The transition metal-catalyzed allylic substitution reaction is a particularly versatile method for the construction of carbon-carbon and carbon-heteroatom bonds. In... (Review)
Review
The transition metal-catalyzed allylic substitution reaction is a particularly versatile method for the construction of carbon-carbon and carbon-heteroatom bonds. In this regard, the rhodium-catalyzed variant has emerged as a powerful method for the regioselective and stereospecific allylic substitution of chiral nonracemic secondary and tertiary allylic carbonates with a variety of carbon- and heteroatom-based nucleophiles. In addition, recent developments have made the analogous enantioselective process possible using prochiral nucleophiles with achiral allylic electrophiles, which represents a significant advance in this area. In this Perspective, the discovery, development and applications of these conceptually orthogonal strategies to target-directed synthesis are discussed, with a particular emphasis given to those methods developed in our laboratory.
Topics: Allyl Compounds; Catalysis; Chemistry Techniques, Synthetic; Rhodium; Stereoisomerism
PubMed: 30183287
DOI: 10.1021/acs.joc.8b00583 -
Organic Letters Jun 2022We describe a Xantphos-containing dinuclear palladium complex-enabled geminal aminoallylation of diazocarbonyl compounds, which selectively provides a range of...
We describe a Xantphos-containing dinuclear palladium complex-enabled geminal aminoallylation of diazocarbonyl compounds, which selectively provides a range of quaternary α-amino esters. Direct N-H insertion, allylic alkylation of amino nucleophiles, and diene formation were not observed under standard conditions. Mechanistic studies indicated that a relayed pathway via allylation of the N-H insertion product or [2,3]-sigmatropic rearrangement of an ylide intermediate was unlikely.
Topics: Alkylation; Allyl Compounds; Azo Compounds; Catalysis; Palladium; Polyenes
PubMed: 35657704
DOI: 10.1021/acs.orglett.2c01399 -
Chemosphere Feb 2022Relative rate coefficients of the OH radical -initiated oxidation of allyl methyl sulfide (AMS, HCCHCHSCH) and allyl ethyl sulfide (AES, HCCHCHSCHCH) have been measured...
Relative rate coefficients of the OH radical -initiated oxidation of allyl methyl sulfide (AMS, HCCHCHSCH) and allyl ethyl sulfide (AES, HCCHCHSCHCH) have been measured at atmospheric pressure of synthetic air and 298 K: k= (4.98 ± 1.42) and k= (6.88 ± 1.49) × 10 cm molecule s by means of in situ FTIR spectroscopy. In addition, the molar yields of the main reaction products of AMS with OH radicals formed in the absence and presence of nitric oxides (NO) were determined to be the following: sulfur dioxide (95 ± 12) % and (51 ± 12) % for acrolein (50 ± 9) % and (41 ± 9) %. In the reaction of AES with OH radicals, the following molar yields were obtained: for sulfur dioxide (88 ± 13) % and (56 ± 12) % for acrolein (36 ± 9) % and (41 ± 9) %. The present results suggest that the abstraction at C3 plays an important role in the oxidation mechanism as the addition to the double bond. This work represents the first study of the OH radical interaction with AMS and AES carried out under atmospheric conditions. The atmospheric implications were discussed in terms of the atmospheric residence times of the sulfur-containing compounds studied and the products formed in the presence and absence of NOx. SO formation seems to be the main fate of the gas-phase allyl sulfides oxidation with significant acidifying potentials and short-chain aldehydes production like formaldehyde and acetaldehyde.
Topics: Allyl Compounds; Kinetics; Physics; Sulfides
PubMed: 34653479
DOI: 10.1016/j.chemosphere.2021.132546 -
Journal of the American Chemical Society Aug 2022An iridium-catalyzed stereoselective coupling of allylic ethers and alkynes to generate 3,4-substituted 1,5-enynes is reported. Under optimized conditions, the coupling...
An iridium-catalyzed stereoselective coupling of allylic ethers and alkynes to generate 3,4-substituted 1,5-enynes is reported. Under optimized conditions, the coupling products are formed with excellent regio-, diastereo-, and enantioselectivities, and the protocol is functional group tolerant. Moreover, we report conditions that allow the reaction to proceed with complete reversal of diastereoselectivity. Mechanistic studies are consistent with an unprecedented dual role for the iridium catalyst, enabling the propargylic deprotonation of the alkyne through π-coordination, as well as the generation of a π-allyl species from the allylic ether starting material.
Topics: Alkynes; Allyl Compounds; Catalysis; Ethers; Iridium; Stereoisomerism
PubMed: 35976157
DOI: 10.1021/jacs.2c07297 -
European Journal of Pharmacology Feb 2021Diallyl disulfide (DADS), an oil-soluble sulfur compound that is responsible for the biological effects of garlic, displays numerous biological activities, among which... (Review)
Review
Diallyl disulfide (DADS), an oil-soluble sulfur compound that is responsible for the biological effects of garlic, displays numerous biological activities, among which its anti-cancer activities are the most famous ones. In recent years, the pharmacological effects of DADS other than its anti-carcinogenic activities have attracted numerous attentions. For example, it has been reported that DADS can prevent the microglia-mediated neuroinflammatory response and depression-like behaviors in mice. In the cardiovascular system, DADS administration was found to ameliorate the isoproterenol- or streptozotocin-induced cardiac dysfunction via the activation of the nuclear factor E2-related factor 2 (Nrf2) and insulin-like growth factor (IGF)-phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) signaling. DADS administration can also produce neuroprotective effects in animal models of Alzheimer's disease and protect the heart, endothelium, liver, lung, and kidney against cellular or tissue damages induced by various toxic factors, such as the oxidized-low density lipoprotein (ox-LDL), carbon tetrachloride (CCl), ethanol, acetaminophen, Cis-Diammine Dichloroplatinum (CisPt), and gentamicin. The major mechanisms of action of DADS in disease prevention and/or treatment include inhibition of inflammation, oxidative stress, and cellular apoptosis. Mechanisms, including the activation of Akt, extracellular signal-regulated kinase 1/2 (ERK1/2), protein kinase A (PKA), and cyclic adenosine monophosphate-response element binding protein (CREB) and the inhibition of histone deacetylases (HDACs), can also mediate the cellular protective effects of DADS in different tissues and organs. In this review, we summarize and discuss the pharmacological effects of DADS other than its anti-carcinogenic activities, aiming to reveal more possibilities for DADS in disease prevention and/or treatment.
Topics: Allyl Compounds; Anti-Inflammatory Agents; Anticarcinogenic Agents; Antioxidants; Disulfides; Humans
PubMed: 33359648
DOI: 10.1016/j.ejphar.2020.173803 -
Angewandte Chemie (International Ed. in... Jun 2022Catalyst-controlled regiodivergent catalysis is a vital chemical tool that allows efficient access to large collections of structurally diverse molecules from a common...
Catalyst-controlled regiodivergent catalysis is a vital chemical tool that allows efficient access to large collections of structurally diverse molecules from a common precursor but remains a challenge. We report a catalyst-controlled, tunable, and predictable regiodivergency in transforming the internal aliphatic propargyl esters into diverse libraries of highly substituted 1,3-dienyl and allyl products by Pd-catalysis. Depending on the ligand employed, the palladium catalyst can involve two typical approaches: electrophilic palladium catalysis and a sequential oxidative addition-reductive elimination pathway. This regiodivergent protocol endows facile access to four regioisomers with high regio- and stereoselectivity from the common propargyl esters. In terms of synthetic utility, a notable feature of this protocol is amenable to structural diversification of bioactive relevant molecules, enabling rapid assembly of many useful structural analogs of pharmaceutical candidates.
Topics: Allyl Compounds; Catalysis; Esters; Ligands; Palladium; Stereoisomerism
PubMed: 35322509
DOI: 10.1002/anie.202203835 -
Chemistry, An Asian Journal Jul 2021Quaternary stereocenters are of great importance to the three-dimensionality and enhanced properties of new molecules, but the synthetic challenges in creating... (Review)
Review
Quaternary stereocenters are of great importance to the three-dimensionality and enhanced properties of new molecules, but the synthetic challenges in creating quaternary stereocenters greatly hinder their wide use in drug discovery, organic material design, and natural product synthesis. The asymmetric allylic alkylation (AAA) of allylic substrates has proven to be a powerful methodology for enantioselective formation of structure skeletons bearing single or more quaternary carbon centers in modern asymmetric organocatalysis. AAA has certain advantages in constructing the tetrasubstituted stereocenters, including but not limited to mild reactive conditions, effective reaction rates, new functional group introduction, and carbon chains length extension. This review outlines the key considerations in the application of AAA reactions and summarizes the recent progress of AAA reactions in the enantioselective synthesis of products containing quaternary stereocenters. Meanwhile, a detailed discussion of the AAA reactions such as ligands, scope of substrates, transformations and the general reaction mechanisms is also provided. We hope this review could stimulate further advances in much broader areas, including organic synthesis, asymmetric catalysis, C-H activation, and symmetrical pharmaceutical chemistry.
Topics: Alkylation; Allyl Compounds; Catalysis; Stereoisomerism; Transition Elements
PubMed: 34014613
DOI: 10.1002/asia.202100432 -
Journal of the American Chemical Society Apr 2021In this article, we advance Rh-catalyzed hydrothiolation through the divergent reactivity of cyclopropenes. Cyclopropenes undergo hydrothiolation to provide cyclopropyl...
In this article, we advance Rh-catalyzed hydrothiolation through the divergent reactivity of cyclopropenes. Cyclopropenes undergo hydrothiolation to provide cyclopropyl sulfides or allylic sulfides. The choice of bisphosphine ligand dictates whether the pathway involves ring-retention or ring-opening. Mechanistic studies reveal the origin for this switchable selectivity. Our results suggest the two pathways share a common cyclopropyl-Rh(III) intermediate. Electron-rich Josiphos ligands promote direct reductive elimination from this intermediate to afford cyclopropyl sulfides in high enantio- and diastereoselectivities. Alternatively, atropisomeric ligands (such as DTBM-BINAP) enable ring-opening from the cyclopropyl-Rh(III) intermediate to generate allylic sulfides with high enantio- and regiocontrol.
Topics: Allyl Compounds; Catalysis; Coordination Complexes; Cyclopropanes; Ligands; Rhodium; Stereoisomerism; Sulfhydryl Compounds; Sulfides
PubMed: 33856804
DOI: 10.1021/jacs.1c00939 -
Organic Letters Mar 2021Although substituted benzimidazoles are common substructures in bioactive small molecules, synthetic methods for their derivatization are still limited. Previously,...
Although substituted benzimidazoles are common substructures in bioactive small molecules, synthetic methods for their derivatization are still limited. Previously, several enantioselective allylation reactions of benzimidazoles were reported that functionalize the nucleophilic nitrogen atom. Herein we describe a reversal of this inherent selectivity toward -allylation by using electrophilic -OPiv benzimidazoles with readily available 1,3-dienes as nucleophile precursors. This CuH-catalyzed approach utilizes mild reaction conditions, exhibits broad functional-group compatibility, and exclusively forms the C2-allylated product with excellent stereoselectivity.
Topics: Allyl Compounds; Benzimidazoles; Catalysis; Copper; Molecular Structure; Polyenes; Stereoisomerism
PubMed: 33646778
DOI: 10.1021/acs.orglett.1c00306 -
Organic Letters Nov 2017A direct, mild, and general method for the enantioselective allylsilylation of aldehydes with allyl chlorides is reported. The reactions are effectively catalyzed by 5...
A direct, mild, and general method for the enantioselective allylsilylation of aldehydes with allyl chlorides is reported. The reactions are effectively catalyzed by 5 mol % of n-BuNBr, and this rate acceleration allows the use of complex allyl donors in fragment-coupling reactions and of electron-deficient allyl donors. The results are (1) significant progress toward a "universal" asymmetric aldehyde allylation reaction that can reliably and highly stereoselectively couple any allyl chloride_aldehyde combination and (2) the discovery of a novel mode of nucleophilic catalysis for aldehyde allylsilylation reactions.
Topics: Aldehydes; Allyl Compounds; Catalysis; Molecular Structure; Stereoisomerism
PubMed: 29068688
DOI: 10.1021/acs.orglett.7b03193