Alkylation-acylation sequence

Tetralone 31 could also be synthesized much more efficiently by employing a chemoselective ketone reduction of 32 to give the lactone 33. A double Friedel-Crafts alkylation/acylation sequence employing a variety of Lewis or protic acids and benzene gave the tetralone 31 directly. Triflic acid and HF produced the highest yields of tetralone, presumably through the intermediacy of the diaryl acid 34 (Scheme 6)... 

The reaction of 52 with BuLi followed by alkylation with alkyl halides gave the silyl selenides 53. The repetition of a similar operation with BuLi and acyl chlorides afforded selenol esters in good yields. Selenol ester was also obtained in a good yield when the order of the alkylation/acylation sequence was changed. 

Both type 1 and type 2 azole N-oxides like 1 and 9 upon alkylation, acylation, sulfonylation, phosphorylation, or silylation at the oxygen atom give rise to highly reactive N-alkyloxyazolium or N-acyloxyazolium salts, etc., (abbreviated common term oxyazolium salts) which can undergo a series of exquisite and useful reactions with nucleophiles, bases, and electrophiles. In most cases the whole sequence can be run in one pot. Reactions of this kind are discussed in the sections dealing with the individual azole N-oxides. A brief overview, listing the reactions of this kind that have been observed in the azole N-oxide series, is presented below. Some of these reaction types have been observed in a few cases only and... 

Alkylation of iV-oxides usually takes place firstly at the oxygen <895773,905795,91CHE802) as does acylation <89TL4353, 905795>. In order to obtain 3-alkylimidazole 1-oxides an acylation-alkylation-deacylation sequence can be followed (Scheme 118) <905795). 

A more general route for this type of chiral bicyclic lactam is based on a metalation from a Meyers lactam (198) followed by alkylation, acylation, or sulfenylation to give the a-substituted bicyclic unsaturated lactams. These compounds were converted to a, -unsaturated derivatives (199) by a metalation-selenation-oxidative elimination sequence that proceeded in good overall yields (Scheme 35) <90T495l>. 

The rates of insertion of ethylene into Pd-alkyl and Pd-acyl bonds have been evaluated for this type of systems, in particular [Pd(R)(C2H4)(L-L)]+ (R = alkyl, acyl L-L = phen, 1,3-diphenylphosphinopropane) [117,118], Lower activation barriers for the acyl complexes were consistently found with AAG (alkyl-acyl) about 2 kcal for the phen complexes and 4 kcal for the phosphino derivatives. Insertion barriers for CO insertion into the Pd-alkyl bond are even lower, making the alternating copolymerization of alkenes and CO possible and almost flawless (a perfect sequence of CO insertion into M-alkyl and alkene insertion into M-acyl with absence of alkene insertion into M-alkyl) [119]. 

Because acylation of an aromatic ring can be accomplished without rearrangement it is frequently used as the first step m a procedure for the alkylation of aromatic compounds by acylation-reduction As we saw m Section 12 6 Friedel-Crafts alkylation of ben zene with primary alkyl halides normally yields products having rearranged alkyl groups as substituents When a compound of the type ArCH2R is desired a two step sequence IS used m which the first step is a Friedel-Crafts acylation... 

Friedel-Crafts acylation followed by Clemmensen or Wolff-Kishner reduction is a standard sequence used to introduce a primary alkyl group onto an aromatic ring... 

Acylation. Acylation is the most rehable means of introducing a 3-substituent on the indole ring. Because 3-acyl substituents can be easily reduced to 3-aLkyl groups, a two-step acylation—reduction sequence is often an attractive alternative to direct 3-aLkylation. Several kinds of conditions have been employed for acylation. Very reactive acyl haUdes, such as oxalyl chloride, can effect substitution directiy without any catalyst. Normal acid chlorides are usually allowed to react with the magnesium (15) or 2inc (16) salts. The Vilsmeier-Haack conditions involving an amide and phosphoms oxychloride, in which a chloroiminium ion is the active electrophile, frequentiy give excellent yields of 3-acylindoles. 

Tusek has reported the Clemmensen reduction of acylated crowns such as shown above. This approach constitutes a useful two-step alkylation procedure, although the yields reported for this sequence are not as high as one might wish. Other examples of closely related acylation approaches can be found in recent work by Tashmukhamedova and coworkers ° ° and by Kauer °. 

Oxathiane 101 is readily deprotonated using s-BuLi, and the resulting anion reacts with alkyl halides, ketones, and benzonitrile (85JOC657). The majority of work in this area, however, is due to Eliel and coworkers and has involved chiral 1,3-oxathianes as asymmetric acyl anion equivalents. In the earliest work it was demonstrated that the oxathianes 102 and 103, obtained in enantiomeri-cally pure form by a sequence involving resolution, could be deprotonated with butyllithium and added to benzaldehyde. The products were formed with poor selectivity at the new stereocenter, however, and oxidation followed by addition... 

In an analogous sequence, reductive alkylation of aminoalcohol, 46, with cyclohexanone affords the secondary amine (47). Acylation with benzoyl chloride affords hexylcaine (48) in a reaction that may again involve acyl migration. 

DNA sequencing and. 1113 Electrospray ionization (ESI) mass spectrometry, 417-418 Electrostatic potential map, 37 acetaldehyde, 688 acetamide, 791,922 acetate ion. 43. 53, 56, 757 acetic acid. 53. 55 acetic acid dimer, 755 acetic anhydride, 791 acetone, 55, 56. 78 acetone anion, 56 acetyl azide, 830 acetyl chloride, 791 acetylene. 262 acetylide anion, 271 acid anhydride, 791 acid chloride, 791 acyl cation, 558 adenine, 1104 alanine, 1017 alanine zwitterion, 1017 alcohol. 75 alkene, 74, 147 alkyl halide, 75 alkyne. 74... 

Virtually any alkyl or acyl halide capable of undergoing bimolecular nucleophilic replacement may enter into the Arbusov reaction. The usual reactivity sentence is acyl > primary alkyl > secondary alkyl with a sequence of halides iodide > bromide > chloride. There is some excellent literature on the Arbusov reaction which has been summarized in several reviews [6,22, 74, 78-82],... 

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