Arylation metal-free

A potentially interesting development is the microwave-assisted transition-metal-free Sonogashira-type coupling reaction (Eq. 4.10). The reactions were performed in water without the use of copper(I) or a transition metal-phosphine complex. A variety of different aryl and hetero-aryl halides were reactive in water.25a The amount of palladium or copper present in the reaction system was determined to be less than 1 ppm by AAS-MS technique. However, in view of the recent reassessment of a similarly claimed transition-metal-free Suzuki-type coupling reaction, the possibility of a sub-ppm level of palladium contaminants found in commercially available sodium carbonate needs to be ruled out by a more sensitive analytical method.25 ... 

Direct high-temperature microwave-assisted aminations of a variety of aryl halides [257] or aryl triflates [258] under transition metal-free conditions have also been reported, probably involving a benzyne mechanism. 

The Br0nsted acid catalyzed enantioselective reduction of several methyl-aryl ketimines affords the corresponding amines in good yields and enantioselectivities (Table 4.1). The mild reaction conditions and generally good chemoselectivity of this transfer hydrogenation render this transformation an attractive and metal-free approach to optically active amines. 

The concept of in situ liberation of carbon monoxide would be even more attractive if a metal-free material could serve as the carbon monoxide source. In the ideal carbonylation method, the organic solvent itself could be exploited for controlled generation of carbon monoxide. In 2002, Wan et al. addressed this issue and developed a microwave-promoted carbamoylation process based on the commonly used solvent dimethylformamide (DMF) as the carbon monoxide precursor75. Firstly, it was discovered that aryl dimethyl amides were accessible from the corresponding bromides in the presence of a nucleophilic catalyst, imidazole (Scheme 2.34). Secondly, tertiary benzamides other than dimethylamides were synthesised by addition of 3 equiv of an external amine (Scheme 2.34). 

A mandelamide diastereomer catalyses addition of both aryl- and alkyl-zincs to heteroaromatic aldehydes in high yield and ee, giving heterocyclic propargyl alcohols, under otherwise metal-free conditions 228... 

Another important means of mediation of metal-free catalytic enantioselective Mannich-type reactions is via electrophilic activation of the preformed imines by chiral Bronstedt acids [7, 8, 46], By using this strategy Terada and coworkers performed chiral phosphoric acid-catalyzed direct asymmetric Mannich-type reactions between Boc-protected imines and acetoacetone that furnished aryl /3-amino... 

Iodonium-ion-promoted intramolecular arylation of allyloxybenzenes 467 provides a metal-free approach to anti-substituted 3-iodochromans 468 (Equation 194) <2004JA3416>. 

Although the Heck reaction may be efficiently employed for synthesis, it has its limits that should not go unmentioned the Heck reaction can not—at least not intermolecularly—couple alkenyl triflates (-bromides, -iodides) or aryl triflates (-bromides, -iodides) with metal-free aromatic compounds in the same way as it is possible with the same substrates and metal-free alkenes. The reason is step 4 of the mechanism in Figure 16.35 (part II). If an aromatic compound instead of an alkene was the coupling partner the aromaticity with this carbopallada-tion of a C=C double bond would have to be sacrificed in step 4. Typically, Heck reactions can only be run at a temperature of 100 °C even if they proceed without any such energetic effort. This is why this additional energetically demanding loss of aromaticity is not feasible. 

Dichiarante, V. and Fagnoni, M. (2008) Aryl cation chemistry as an emerging versatile tool for metal-free arylations. Syrdett, (6), 787-800. 

De Carolis, M., Protti, S., Fagnoni, M. and Albini, A. (2005) Metal-free cross-coupling reactions of aryl sulfonates and phosphates through photoheterolysis of aryl-oxygen bonds. Angewandte Chemie, International Edition, 44, 1232-1236. 

Arylboronic esters (Figure 5.39) can be oxidized with H202 in acetic acid to give aryl borates, which can then be hydrolyzed to provide phenols. The mechanism for this oxidation is similar to that for the OOH- oxidation of trialkylboranes and is discussed in Section 11.4.3. In combination with the frequently simple synthesis of arylboronic esters one can thus achieve the overall conversions Ar—H — Ar—OH or Ar—Br —> Ar—OH in two or three steps. There is no metal-free alternative for these hydroxylations even if occasionally there are readily applicable roundabout routes, referred to in Figures 11.32 and 11.34. 

Summary Bis(trimethylsilyl)mercury cleanly reacts at low temperature with chloroiminium chlorides to form stable metal-free cyclic and acyclic diaminocarbenes as well as aryl-, oxy-, chloro-, hydrogeno- and alkyl-amino carbenes. The aryl-, chloro-and hydrogeno-amino carbenes were formed as transient intermediates that undergo dimeri2ation into the corresponding alkenes, which were isolated in good yields. Alkyl-and oxy-amino carbenes were observed at low temperature by C NMR spectroscopy. 

There are a few efficient methods for the stereoselective synthesis of vinyl halides, and this transformation remains a synthetic challenge. Research by S. Roy showed that the Hunsdiecker reaction can be made metal free and catalytic catalytic Hunsdiecker reaction) and can be used to prepare ( )-vinyl halides from aromatic a,p-unsaturated carboxylic acids. The unsaturated aromatic acids were mixed with catalytic amounts of TBATFA and the A/-halo-succinimide was added in portions over time at ambient temperature. The yields are good to excellent even for activated aromatic rings which do not undergo the classical Hunsdiecker reaction. The fastest halodecarboxylation occurs with NBS, but NCS and NIS are considerably slower. The nature of the applied solvents is absolutely critical, and DCE proved to be the best. This strategy was extended and applied in the form of a one-pot tandem Hunsdiecker reaction-Heck coupling to prepare aryl substituted (2 ,4 )-dienoic acids, esters, and amides. 

Sinha et al. [7] for the first time reported a highly efficient and recyclable combination of Candida antarctica lipase B (CAL-B) and nentral ionic liqnid [hmim] [Br] for metal-free activation in the chemoselective oxidation of aryl alcohols. Initial study was carried out using 4-methoxyphenyl propanol, as substrate, and HjOj at 40°C in the presence of CAL-B/[hmim][Br], thereby providing aldehyde in 90% yield after 16 h. Increasing the reaction temperature to 60°C significantly brought down the reaction time from 16 to 8 h (Scheme 14.7). 

Sharma UK, Sharma N, Kumar R, Kumar R, Sinha AK (2009) Biocatalytic promiscuity of lipase in chemoselective oxidation of aryl alcohols/acetates a unique synergism of CAL-B and [hmim][Br] for the metal-free activation. Org Lett 11 4846-4848... 

---