Metal-free acylation

In related work a library of 1,458 peptide ligands and various metal salts was tested in hydrolysis reactions of (p-nitrophenyl)phosphates.35 An active substructure composed of polymer-bound histidine in combination with Eu3+ was identified by further dissecting the original hit structure. It needs to be pointed out that catalytically active polymer beads can also be tested for catalytic activity using IR-thermography. In a seminal paper this was demonstrated using 7,000 encoded polymer beads prepared by split-and-pool methods, specifically in the metal-free acylation of alcohols.36... 

The acyl radical formed from acrolein, maintaining its coordination with a catalyst, may react preferably with oxygen, rather than decompose to produce carbon monoxide, though it is generally believed that a free acyl radical is formed after the abstraction of aldehyde hydrogen by a metal. In such a case, the catalyst metal is considered as behaving as a mononuclear, not a binuclear complex. The molecular weight of the catalyst recovered from the oxidation solution was measured (Table V). 

The chiral bicyclic phosphines 5 (and in particular 5a [7b]) are currently the most active phosphorus-based acylation catalysts, enabling use of low reaction temperatures. Under these conditions (i.e. —40 °C) selectivity factors as high as 370-390 were achieved (Scheme 12.2). This is the best selectivity factor ever reported for metal-free, non-enzymatic kinetic resolution. As a consequence, very good enantiomeric purity of both the isobutyric esters 7 and the remaining alcohols 6 was obtained, even at substrate conversions approaching 50% (Scheme 12.2) [7, 8],... 

The a-amino group of amine component V and the imidazole of IV are suggested to be involved in the metal binding from the shift of their dissociation constants. That is, the pKa-values of the amino and imidazole groups in metal-free BLM A2 are 7.4 and 4.7 respectively. However, in copper-chelated BLM A2 there is no ionizable group with a pKa-value between 4 and 9. Furthermore, acylation of the a-amino... 

Metal-free Alkylations by Acyl Halides on Polymeric Supports... 

The value of the metal complexation results from control of the reaction, rather than any activation, Lewis acids being excellent catalysts for diene polymerization. Friedel-Crafts acylations of diene complexes have been used for the preparation of dienes, with decomplexation following carbonyl reduc-tion. 5 Decomplexation to afford dienones has been less explored. The intermediate cationic o -complex on treatment with triethyl phosphite or triphenylphosphine affords metal-free. y-unsaturated phospho-nates or phosphonium salts (Scheme 19). The initial s-cis conformation of the diene fragment of the... 

A particular case of metal-free bisacylation is reported concerning the reaction of para-substituted N,N-dimethylanilines with oxalyl chloride promoted by l,4-diazabicyclo(2.2.2)octane (DABCO) for the production of compounds 51 (Scheme 2.23). i The reaction requires anearly stoichiometric mixtureof oxalyl chloride, DABCO, andN,N-dimethylaniline, and proceeds through ortho-C-acylation followed by N-acylation-mono-demethylation. The base presumably takes part in the initial production of the oxalyl chloride acylium salt as well as in the demethylation step. 

Reports describing the use of Minisci-type reaction conditions to functionalize pyrazine ring systems emerged in 2014. Siddaraju and coworkers devised a metal-free Minisci reaction, which they applied to the acylation of quinoxaline (Scheme 54) (14JOC3856). Reaction of quinoxaline (0.24 mmol) with the respective benzaldehyde in the presence of tetrabutyl-ammonium bromide (30mol%) and ammonium persulfate (2 equivalents) in 1,2-dichloroethane at 110°C provided (4-methoxyphenyl)(quinoxalin-2-yl)methanone in 66% yield and quinoxalin-2-yl(p-tolyl)methanone in 44% yield. 

Scheme 9.8 Synthesis of 2-acyl benzothiazole through metal-free sp C-H functionalization.

The one-pot synthesis of 2-substituted-3-carboxychromones is readily attained by the reaction of 3-oxo-3-(2,6-di luorophenyl)propanoates and acyl chlorides (13CC5313) and of 3-[2-(methoxymethoxy)phenyl]propio-lates and aldehydes followed by DDQ oxidation of the formed chroma-nones (13T647), via transition metal-free approaches. Palladium(II) -catalyzed cascade carbonylative cyclization of 2-bromophenols and terminal alkenes gives chromones 44 in moderate to good yields. Variation on the amine used in the catalytic system led to aurones 45 as major products (Scheme 74) (13TL1802). 

Zhao and Du s group [63] developed a metal-free cross-dehydrogenative coupling (CDC) of various 2-(A -arylamino)aldehydes 79 for direct aryl-aldehyde C (sp )-C(sp ) bond formation to provide a convenient approach for the synthesis of biologically important acridone derivatives 80 (Scheme 19). PIDA was used in combination with a substoichiometric amount of benzoyl peroxide as radical initiator for this oxidative intramolecular annulation reaction which presumably proceeds via the intermediacy of acyl radicals 81. 

The optically active 2-acyl-2,3-dihydrobenzofuran skeletrm is a key structure in several biologically active compounds. The asymmetric oxidation of ketophenols 68, catalyzed by in situ generated chiral quaternary ammonium (hypo)iodite salts 70, with hydrogen peroxide as cooxidant, opened up a new enantioselective, metal-free route to 2-acyl-2,3-dihydrobenzofurans 69 (Scheme 27) [85]. The substiments at the 3,3 -positions of the binaphthyl moiety of the salt 70 played an important role in the enantioselectivity as well as in the chemical yield of the reaction. The products are formed in up to 96% ee. 

The transition metal-free synthesis of A-acyl diarylamines has been achieved through a three-step process (Scheme 3.62) [68]. Although many steps were involved in this approach, moderate to good yields of the desired compounds were obtained for most substrates. 

Acylphosphines can be prepared through the metal-free treatment of acyl chlorides with secondary phosphines (Scheme 4.316) [480]. This approach is high yielding... 

An XD, Yu S (2015) Visible-light-promoted and one-pot synthesis of phenanthridines and quinolines from aldehydes and o-acyl hydroxylamine. Org Lett 17(ll) 2692-2695 Tang C, Yuan Y, Jiao N (2015) Metal-free nitrogenation of 2-acetylbiphenyls expeditious synthesis of phenanthridines. Org Lett 17(9) 2206-2209... 

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