Electronic diversity

The Jacobsen-Katsuki epoxidation reaction is an efficient and highly selective method for the preparation of a wide variety of structurally and electronically diverse chiral epoxides from olefins. The reaction involves the use of a catalytic amount of a chiral Mn(III)salen complex 1 (salen refers to ligands composed of the N,N -ethylenebis(salicylideneaminato) core), a stoichiometric amount of a terminal oxidant, and the substrate olefin 2 in the appropriate solvent (Scheme 1.4.1). The reaction protocol is straightforward and does not require any special handling techniques. 

Under carefully controlled conditions the selective mono bromination of an electronically diverse range of acetophenone derivatives can be realized using the polymer-supported pyridinium perbromide reagent. The resultant a-bromoketone... 

Additionally, You reported a F-C reaction of indole with electronically diverse aryl aldimines (Scheme 5.8) [16]. In general, products could be obtained in excellent yields and enantioselectivities in short reaction times. 

Finally, the remarkably simple solution came from Evans et al. [21a] and researchers of DuPont [21b] simultaneously. Their method allows the coupling of structurally and electronically diverse phenols and aryl boronic acids in the presence of copper]11) acetate, trie-thylamine or pyridine, and molecular sieves at ambient temperature (Scheme 5). Even phenolic amino acid derivatives react smoothly without racemization. The only limitation has been observed when using orfho-heteroatom substituted boronic acids which resulted in lower product yields. The initial step in the proposed pathway (Scheme 6) is the trans-metallation of the boronic acid residue with the copper salt. 

In a parallel synthesizer, electronically diverse libraries of more than 150 substituted coumarins 26 could be readily constructed in solution. Screening of the optical properties of the fluorophore ensemble gave rise to the identification of several library members with high fluorescence quantum yields (Fig. 5.10). 

The oligothiophenes 27 bear phenyl groups in the 3 -position of the thiophene cores that are para-substituted with electronically diverse functional groups (R = CF3, H, CH3, OCH3). Here, the phenyl spacers enhance the solubility of the oligomers and warrant the electronic communication between the elements of diver-... 

As evidenced by the treatment of three (Z)-(/l-arylsulfonyl-l-decenyl)phenyliodonium fluoroborates with triethylamine, the presence of electronically diverse substituents (H,p-N02, / -MeO) in the arylsulfonyl groups appears to have little impact on their migratory aptitudes (equation 239)32. Indeed, among six [(/1-alkyl-/l-arylsulfonyl)vinyl]iodonium salts that have been investigated, the cyclopentene/alkyne ratios show little variability (i.e. 70 30 to 80 20)32. Finally, the presence of an appropriately placed alcohol function in the side chain of a (/l-sulfonylvinyl)iodonium salt has been shown to completely suppress migration in favor of insertion (equation 240)32. 

After coupling of (hetero)aroyl chlorides 7 and terminal alkynes 4, ortho-ammo thiophenols 52 and acetic acid are added and reacted in the same reaction vessel under dielectric heating for 30 min at 60°C to furnish 2,4-disubstituted benzo[h][l, 5] thiazepines 53 via a coupling-addition-cyclocondensation sequence (Scheme 31) [193]. In the concluding heterocyclization step, dielectric heating is clearly superior over conductive heating. Although the Michael addition and cyclocondensation are essentially completed after 10 min at 60°C in the microwave cavity for electronically diverse substitution a reaction time of 30 min at 60°C has proven to be optimal. In contrast to 2,4-disubstituted benzo[h][l,4]diazepines 51 (vide supra), benzo[h] [1, 5]thiazepines 53 are essentially nonfluorescent. 

The lanthanides, for which the general symbol Ln is used here, have electron configurations with fis in common and a variable occupation of the 4f level. Classically called the Rare Earths, they are also referred to as the inner-transition elements because the 4f electron build-up takes place in the fourth quantum level, below the 5s, 5p and 6s electrons. As the electronic diversity between the atoms is at some depth the elements are very similar chemically. The small differences in properties arise principally from the... 

It was also possible to carry out an analogous intermolecular version of the alkylation/carboxylation process between 2-substituted indoles and styrenes (Scheme 45) [73]. While sterically and electronically diverse styrene derivatives reacted with moderate to good yields (40-78%), indoles without substitution at C2 failed to undergo efficient reaction. The reactions were always selective for the indole C3-position (as C2 was blocked) and produced products substituted to the phenyl ring. 

Aryl bezenesulfonates and aryl tosylates (ArOTs) are cheap and easily prepared compared to their triflate counterparts. Buchwald reports that these useful sulfonates can be catalytically animated using L7 (XPhos) as a ligand.42 A variety of base and solvent combinations using f-BuOH was found to be necessary depending upon the nature of the aryl tosylate and amine. In all of the aforementioned examples, a sterically and electronically diverse library of bi-aryl phosphine ligands allowed Buchwald and coworkers to specifically optimize reaction conditions for most ArX/amine combinations. 

Proazaphosphatrane bases were used for palladium catalysed Stille reactions of aryl chlorides. These bases efficiently catalyse the coupling of electronically diverse aryl chlorides with an array of organotin reagents. The catalyst system based on benzyl (Bn)-proazaphosphatrane is active for the synthesis of sterically hindered biaryls. The use of the proazaphosphatrane allows room temperature coupling of aryl bromides and it also permits aryl triflates and vinyl chlorides to participate in Stille coupling [69] (Scheme 5.47). 

Based on their successes in developing catalytic asymmetric Fischer indole synthesis, List and co-workers further carried out [3,3]-rearrangement reactions of At,At -binaphthyl hydrazines to deliver BINAM products. In this case, (i )-35 was also proved to be the best catalyst. The addition of weakly acidic CG-50 resin as an additive could allow the reaction to be performed at a relatively low catalyst loading (5 mol%). A number of Af,Ar-binaphthyl hydrazine substrates with electronically diverse substituents could be converted to their corresponding products in good yields and enantioselectivity. 

Moderate to good yields of 3-substituted quinolines 598 were achieved, and the reaction s tolerance for electronically diverse substituents on the aromatic ring promises to make this a general and preferred route to these quinolines (Scheme 4.176). 

The flexible synthetic strategy enables access to electronically diverse substituted ferrocenyl isoxazoles 13 in moderate to good yields. 

Aroyl chlorides 4 with electronically diverse substituents are equally well tolerated whereas pivaloyl chloride only leads to a diminished yield of 10%. In contrast, the substituents on the terminal alkyne 5 can be easily varied between aromatic and aliphatic, although aliphatic substituents generally result in lower yields. A TMS group introduced through the alkyne gets cleaved under cyclocondensation conditions, thus leading to 2-substituted ct-carboUnes. Different substituents on the amino IH-indole 33 do not... 

Several tandem reaction sequences have been developed for indole synthesis featuring a Buchwald-Hartwig aryl amination as one component. For instance, a tandem double JV-arylation of substrate 5 leads to indoles 6 through a cascade of C-N bond forming reactions. A range of structurally and electronically diverse amines can be used successfully in this transformation. 

The same group reported an extension of the direct alkylation of (benz)oxazoles with various alkyl bromides and chlorides by using the stronger base lithium tert-butoxide (Scheme 19.23) [38]. 5-Aryloxazoles containing electronically diverse substituents such as CFj and OMe were also alkylated successfully. Various linear alkyl chains were introduced, such as phenylpropyl, citronellyl, or octyl, affording interesting lipophilic molecules. The optimized reaction conditions failed to apply to benzothiazoles, and the authors had to turn their attention to nickel catalysis to achieve the corresponding alkylation (Section 19.2.3). Experiments were run to understand the reaction mechanism that presumably involves Sj 2-type oxidative addition of the alkyl halide to palladium(O) followed by transmetallation by the in situ-lithiated (benz)oxazole (Scheme 19.24). 

More recently, a palladium-catalyzed intramolecular C-H arylation with mesylated compounds was reported by Kalyani and co-workers. A sequential mesylation-arylation protocol using phenols as substrates vras described as well. This method allows for the synthesis of diverse heterocyclic motifs, including dibenzofurans, carbazoles, and indoles, in good yields (Scheme 2.30). The intermolecular aiylations were efficient for the coupling of azoles with electronically diverse mesylates. 

The Lu group demonstrated the Pd-catalyzed arylation of naphthalene using aryl iodides in the presence of stoichiometric AgOCOCF (Scheme 24.10) [14]. Electronically diverse aryl iodides effectively participate in these reactions to afford the corresponding products in good yields. The a-isomCT is the major product in aU cases regardless of the electronic nature of the aryl iodides. The Pd " pathway is proposed to be operative under these reaction conditions, primarily because Pd" catalysts do not afford the desired biaryl products in the absence of the AgOCOCF. ... 

The direct borylation of arenes is an attractive strategy for accessing synthetically useM arylboron reagents. Iridium complexes have emerged as the catalyst of choice for the selective borylation of arenes using HB(pin) or Bj(pin)j [67], Extensive studies by the Hartwig, Ishiyama, and Miyanra groups have led to the identification of the Ir OMe(cod)j/dtbpy as the optimal catalyst system for these transformations [68-70], As illustrated in Scheme 24.59, electronically diverse arenes are borylated at room temperature to afford the products in excellent yields. The site-selectivity of these... 

Sames et al. developed an a-alkenylation of cycUc ethers to synthesize both annulation and spirocyclization products (Scheme 53) [39]. Four types of electronically diverse hydride donors were investigated and remarkably the selection of suitable catalysts was crucial to the success of cascade processes. As to substrate 137, in which relatively unreactive secondary C-H bond was exploited as hydride donor, no aromatic group was available to stabilize the oxocarbenium generated via [1,5]-HT. Hypervalent platinum catalyst Ptl4 was the optimal catalyst, which affected complete conversion of 137 to furnish the product 138 in 86 % yield, whereas Ptl4 only led to complete decomposition of 141 despite higher reactivity of... 

In Ullman-type coupling, aryl boronic acids are much more efficient coupling partners with amines and phenols as compared with aryl halides. They successfully couple at room temperature in the presence of a copper acetate/triethylamine (or pyridine) catalyst system and the corresponding arylated products were provided in high yields (Scheme 15.20). Similarly, aryl boronic acids are successfully coupled with structurally and electronically diverse substrates such as amides and sulfonamides to afford the corresponding IV-arylated products. 

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