Facile ring-closure cyclization of arenes by nucleophilic C-allylation reaction in ionic liquid (original) (raw)
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ChemInform, 2010
A novel synthetic method using an ionic liquid (IL) for a six-membered ring-closure cyclization is described. The ring-closure cyclization by nucleophilic C-alkylation was achieved with various haloand alkanesulfonyloxyalkyl aromatic compounds in high yields with minimal byproducts using ILs as the reaction media in the absence of any catalyst. For example, the cyclization of 2-(3-methanesulfonyloxy-propoxy)naphthalene (1a) to 2,3-dihydro-1H-naphtho[2,1-b]pyran (2) in IL [bmim] [PF 6 ] proceeded selectively at 150°C for 24 h in 85% yield.
Tetrahedron Letters, 2011
A rapid, economic, and high yielding methodology has been developed for hydroacylation/reduction of activated ketones by using 1,3-bis(2,4,6-trimethylphenyl)imidazolium chloride as a catalyst in combination with triethylamine. The reaction proceeded at an ambient temperature via generating N-heterocyclic carbene in situ that interacted with the (hetero)aryl aldehyde employed. While the reduction of ketones takes place in MeOH, the hydroacylation process was found to be effective in THF for both electron rich and deficient aldehydes.
2012
The development of novel synthetic methods for the rapid and stereoselective preparation of complex molecular scaffolds constitutes the driving force behind organic synthesis. [1] In the past decade, organocatalytic [2] methods have emerged as complementary to organometallic-based techniques for catalysed transformations. In particular, enamine, [3] iminium, [4] and SOMO catalysis, [5] as well as photocatalysis [6] have contributed to the enhanced synthetic utility and versatility of carbonyl compounds. The stereoselective alkylation of carbonyl groups (aldehydes and ketones) has been achieved through conceptually different activation modes. [7] Recently, we introduced the concept of enantioselective S N 1-type alkylations to organocatalysis, [8, 9] and also established the compatibility of indiumA C H T U N G T R E N N U N G (III) Lewis acids with organocatalytic processes mediated by the MacMillan catalyst. [10, 11] The compatibility of indiumA C H T U N G T R E N N U N G (III) salts in these processes creates the possibility of using carbocations that cannot be generated in the presence of Brønsted acids. [12] The stability of the carbocation involved in the process is the primary driving force for these S N 1-type reactions, and their use can be easily rationalized by the work of Mayr et al. [13] In the presence of InBr 3 , allylic alcohols can provide straightforward access to alkylated aldehydes without the use of palladium or iridium salts. [14] Herein, we report an extension to the scope of our methods to include benzylic and benzhydrylic alcohols, substrates which give access to useful intermediates for the synthesis of biologically active enantioenriched diarylethane products. [15] This structural motif has a diverse range of biological properties that include anticancer, antidepressant, and antiviral activity. [16] We envisioned the direct synthesis of enantioenriched diarylethanes from readily available racemic diarylmethanols (Table 1). We have established a correlation between the electrophilicity (E) of the carbenium ion employed in our S N 1-type reaction and the possibility of generating such an ion. Alcohols that form carbenium ions located at À1 or above on the Mayr scale are not reactive with the enamine that is formed in situ with the MacMillan catalyst. [17] Even in the presence of strong acids, the carbenium ions are not formed or are intercepted by water. Alternatively, by using indiumA C H T U N G T R E N N U N G (III) salts (triflate or bromide), the corresponding carbenium ion can be generated from the alcohols and intercepted by the enamine formed in situ with the MacMillan catalyst. [10-11] The compatibility of indiumA C H T U N G T R E N N U N G (III) salts with water, the amine, and an excess of aldehyde is the motivation for investigating this chemistry. The reactions of model substrates 2 a-c were investigated in the presence of different Lewis acids and under various conditions. The 4-MeO derivative 2 a was rather unreactive and afforded the desired product in 75 % yield as a 1:1 diastereomeric mixture in 76 and 59 % ee after 24 h, with InBr 3 as the Lewis acid in CH 2 Cl 2 (Table 1, entry 1). Many other benzhydrylic derivatives bearing the methoxy substituent were tested, but the reactions gave poor results. In our preceding publications we have established that steric hindrance of the incoming carbenium ion controls the stereoselectivity of the reaction. [11] Therefore, to increase the stereoselectivity and reactivity, derivatives 2 b and 2 c were tested. The reaction conditions were carefully optimized by varying the solvent, Lewis acid, and MacMillan catalyst used in the reaction. Substrate 2 c is more sterically demanding because of the diphenyl substituent. The introduction of an ortho substituent results in more steric hindrance in the carbenium ion, which in turn introduces a steric bias for the enamine that is formed in situ with the MacMillan catalyst. In general, different Brønsted or Lewis acids are able to promote the formation of the corresponding carbenium ion and are compatible with secondary amines and excess aldehydes. However, only InA C H T U N G T R E N N U N G (OTf) 3 ensured high stereoselectivity in this reaction. By varying the solvent excellent stereoselectivity was obtained with catalyst 3 b. Different benzhydrylic substituents were then tested and the data obtained are shown in Table 2. The diastereoselectivity is
An efficient organocatalytic method for constructing biaryls through aromatic C–H activation
Nature Chemistry, 2010
The direct functionalization of C-H bonds has drawn the attention of chemists for almost a century. C-H activation has mainly been achieved through four metal-mediated pathways: oxidative addition, electrophilic substitution, s-bond metathesis and metal-associated carbene/nitrene/oxo insertion. However, the identification of methods that do not require transition-metal catalysts is important because methods involving such catalysts are often expensive. Another advantage would be that the requirement to remove metallic impurities from products could be avoided, an important issue in the synthesis of pharmaceutical compounds. Here, we describe the identification of a cross-coupling between aryl iodides/bromides and the C-H bonds of arenes that is mediated solely by the presence of 1,10-phenanthroline as catalyst in the presence of KOt-Bu as a base. This apparently transition-metal-free process provides a new strategy with which to achieve direct C-H functionalization.
Cyclization Reactions for the Synthesis of Phthalans and Isoindolines
Synthesis
Oxygen and nitrogen heterocycles are present in a vast number of natural substrates and biologically active molecules. In particular, phthalan and isoindoline subunits are found in many classes of products such as antibiotics, antioxidants, antimycotics, pigments, and fluorophores. Therefore several procedures dedicated to the construction of these heterocycles have been developed. In this review, a detailed analysis of the literature data regarding the synthesis of these nuclei via cyclization reactions is reported.1 Introduction2 Phthalans2.1 Oxa-Pictet–Spengler Reaction2.2 Garratt–Braverman Cyclization2.3 Diels–Alder and Related Reactions2.4 [2+2+2] Cyclotrimerization of Alkynes2.5 Cycloetherification of ortho-Substituted Aromatics2.6 Tandem Carbonylative Sonogashira Coupling–Cyclization Reactions3 Isoindolines3.1 Amination of Dihalides3.2 Intramolecular Hydroamination3.3 Diels–Alder and Related Reactions3.4 [2+2+2] Cycloaddition Reactions3.5 Tandem Carbonylative Sonogashira Coup...