Base-free conditions

Chlorides are inert. However, the reaction ofp-chlorobenzophenone (9) with a styrene derivative proceeds satisfactorily at 150 C by u.sing dippb [l,4-bis(-diisopropylphosphino)butane] as a ligand to give the stilbene derivative 10. However, dippp [l,3-bis(diisopropylphosphino)propane] is an ineffective ligand[13]. On the other hand, the coupling of chlorobenzene with styrene proceeds in the presence of Zn under base-free conditions to afford the cis-stilbene 11 as a main product with evolution of H . As the ligand, dippp is... 

The palladium- and copper-mediated C-2 arylation of thiazole with 4-iodoanisole under ligandless and base-free conditions provides 2-(4-methoxyphenyl)thiazole in good yield <06EJOC1379>. However, the scope of this selective C-2 arylation has not been disclosed. 

Table 4.8 Asymmetric transfer hydrogenation of aromatic ketones, catalyzed by [lrH(CO)(PPh3)3]/83 under base-free conditions.

In 1995 Soderquist and Ftirstner independently reported that alkynylborates 67, prepared in situ from 9-OMe-9-BBN and alkynylmetals, effectively cross-couple with aryl and alkyl bromides using a Pd catalyst under base-free conditions at 60 °G. Soderquist and co-workers also reported on the synthesis of alkynylborinates 68, which are easier to isolate (Figure... 

T. Ohkuma, M. Koizumi, K. Muniz, G. Hilt, C. Kabuto, and R. Noyori, tmns-RuH(etal-BH4)(binap)(l,2-diamine) a catalyst for asymmetric hydrogenation of simple ketones under base-free conditions,... 

In several instances similar transformations were conducted under base-free conditions. Thus, heating 7V,7V -diphenylbenzamidine 112 with hydrogen peroxide at 80 °C leads to the formation of 1,2-diphenyl benzimidazole 114 in 67% yield (Scheme 34) (99IZV626). Though the mechanism of this conversion remains unclear,... 

Two methodologies for the direct C-2 arylation of thiazoles have been reported. The first one is mediated by both palladium and copper <07T1970>. Thus, the C-2 arylation of thiazole and benzothiazole with aryl iodides is carried out using copper iodide (2 equiv.) and a catalytic amount of palladium acetate under base-free conditions. The other method involves copper-catalyzed arylation with aryl iodides in the presence of lithium t-butoxide <07JA12404>. In general, reactions with lithium tert-butoxide provide better yields than those with potassium fert-butoxide. In addition, arylation with phenyl bromide, chloride or tosylate fails to provide any desired arylation products. 

The 2-indolinone system has been found in a large number of pharmaceutically active compounds. This framework could be constructed by a tandem Heck-Suzuki reaction sequence [137]. Intramolecular Heck reaction of 390 afforded a cyclized intermediate that, in situ, reacted with boronic acid 187 to produce 391 in a single pot sequence. The reaction made use of copper thiophene-2-carboxylic acid (CuTC) to generate base-free conditions for the Suzuki reaction. 

Functionalization of C - H bonds of heterocycles to C-arylation is an important synthetic reaction that is used to build important bioactive structures. Recently palladium and copper-mediated C-2 arylations of benzimidazole with aryl iodides under ligandless and base-free conditions have been described (Scheme 14) [56]. These reactions show complete selectivity under these conditions and allow for the use of substrates containing base-sensitive groups without their prior protection, such the NH group of benzimidazoles [56,57]. The aryl-substituted benzimidazole compounds were obtained in high purities and yields within 48 hours, and the scheme was also applicable to other azoles. 

Beilina and Rossi also reported a ligand-free approach for die C2-arylation of NH-free indoles (Scheme 15, 06JOC1379, 07T1970). However, this Pd/Cu catalyzed reaction occurring under base-free conditions gave low yields with indoles (although this procedure was very efficient for other substrates, such as NH-free imidazoles). 

As noted above, we began to investigate the reaction under base-free conditions however, the reactions stalled at approximately 50% conversion... 

For other types of conjugated alkenes, a variety of vinyl halides were prepared from the reaction of 1,1-diarylalkenes with NCS in good yields under mild and base-free conditions. The reaction proceeds well with electron-rich diarylalkenes, such as those with methoxy substituents on the aromatic rings. 4... 

Moreover, under even less basie eonditions, the G2-H bond of the imidazolium nucleus bond can oxidatively add to electron-rieh Ni(0) or Pd(0) eomplexes to generate stable carbene-metal-hydride compounds (Scheme 11). " The 1,3-dimethylimidazolium eation also oxidatively adds to [Pt(PPh3)4] as observed by P NMR, although yields of the product m-[PtH(l,3-dimethylimidazolin-2-ylidene)(PPh3)2]BF4 were rather poor. Interestingly, both the H2 and H5 in imidazolium salts can be activated under neutral conditions, as observed in the reaction of an imidazolium salt upon reaction with a Pd(ii) derivative under base-free conditions where the carbene was formed through the activation of H5 of the imidazolium ring (Scheme 12). ... 

Postsynthetically modified frameworks were also used as heterogeneous catalyst for the same reaction. Proch et al. [104] loaded MOF-177 with platinum nanoparticles via gas-phase infiltration of volatile [MejPtCp ] precursor under reduced pressure followed by reduction under hydrogen pressure. While this material efficiently catalyzes the oxidation of benzylic and allylic alcohols under solvent and base-free conditions at room temperature, it could not be recycled because of stability issues. 

A palladium-catalyzed oxidative C—H/C—H cross-coupling between benzothiazoles 70 and thiazoles 71 is carried out under base-free conditions (14CC3996).This reaction appears to be insensitive to air and moisture and displays high-functional group tolerance. 

Highly regioselective tandem syntheses of 3-halo-5-substituted isoxazoles 3 have been developed from l-copper(I)-alkynes and dihaloformaldoximes under base-free conditions. This methodology inhibits the formation of halonitrile oxides precluding 1,3-dipolar cycloadditions (1,3-DC) (14OL6140). 

Dubbaka, S.R. and Vogel, P. (2005) Palladium-catalyzed desulfitative Mizoroki-Heck couplings of sulfonyl chlorides with mono- and disubstituted olefins rhodium-catalyzed desulfitative Heck-type reactions under phosphine- and base-free conditions. Chem. Eur. J., 11, 2633-41. 

Sugihara, T., Satoh, T. and Miura, M. (2005) Mizoroki Heck type arylation of alkenes using aroyl chlorides under base-free conditions. Tetrahedron Lett., 46, 8269-71. 

Dubbaka and Vogel reported on rhodium-catalysed Mizoroki-Heck-type reactious employing arenesulfonyl chlorides as inexpensive electrophiles. Thereby, styrene derivatives were arylated under base-free conditions. Again, rhodium-alkene complex 89 was found to be significantly more active than phosphine-derived rhodium species (Scheme 10.32) [60],... 

Dubbaka, S.R. and Vogel, P. (2005) Palladium-catalyzed desulfltative Mizoroki-Heck coupling of sulfonyl chlorides with mono- and disubstituted olefins rhodium-catalyzed desulfitative Heck-type reactions under phosphine- and base-free conditions. Chem. Eur. J., 11, 2633 1. Kamigata, N., Ozaki, J.-i., and Kobayashi, M. (1985) Reaction of alkenesulfonyl chlorides with olefins catalyzed by a ruthenium(ll) complex. A novel method for synthesis of ( , )- ,4-diaryl-... 

Another interesting strategy to achieve a waste-minimized Mizoroki-Heck reaction was recently reported by Miura et al. (Scheme 7.13) [31]. Using aroyl chlorides 57, the Mizoroki-Heck reaction proceeded well under base-free conditions, liberating only hydrochloric acid and carbon monoxide as byproducts (57 59). However, due to the particularly waste-intensive preparation of acyl chlorides, it remains questionable whether this procedure would be suitable for large-scale alkene arylation. 

Several variations exist for the classic Sommelet-Hauser rearrangement. The most important concern the use of base-free conditions for the [2,3]-sigmatropic rearrangement based on the fluoride anion induced desilylation of substituted benzyldialkyl-[(trimethylsilyl)methyl] ammonium halides" and the asymmetric versions of Sommelet-Hauser rearrangement that appeared recently in the literature. None of the above has ever been used in a modification of the Gassman indole synthesis. 

During the same year, nano-Cu20 was employed to facilitate the N-arylation of azoles and amines with arylboronic acids (Scheme 4.34). Several Af-aryl azole derivatives could be efficiently assembled at room temperature under base-free conditions (Sreedhar et al., 2008). 

A new protocol for the aUcynylation of various aromatic as well as aliphatic aldehydes (48) and alkynes (109) using ZnO under solvent- and base-free conditions was developed by Hosseini-Sarvari and Mardaneh (2011b) (Scheme 9.33). This demonstrates an important strategy for C-C bond formation in organic chemistry. 

In the presence of molecular sieves under base-free conditions, organic halides were successfully converted into carboxylic acids or esters with water or alcohol, respectively, under carbon monoxide pressure by a palladium catalyst in good yields. ... 

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