A,p-unsaturated ketoximes

A new, eco-friendly o-iodoxy benzoic acid-mediated synthesis of 3,5-dia-rylisoxazoles and 5-arylisoxazole-3-carboxylic acids from a,p-unsaturated ketoximes has been reported (14SC1453). 

Colby et al. [78] disclosed a two-step pyridine synthesis from a,fi-unsaturated imines through alkyne insertion into an alkenyl C-H bond/electrocyclization to form dihydropyridines and subsequent aromatization (Scheme 18.78). Cheng and coworkers [79] concurrently succeeded in obtaining pyridines in one step by using a,P-unsaturated ketoximes, which allow to omit the second aromatization step with oxidant (Scheme 18.79). 

Dry DMF (2mL) was added to a Schlenk tube containing the a,P-unsaturated ketoxime O-pentafluorobenzoate (0.1 mmol), the boronic acid (0.12 mmol), 4 A molecular sieves (100 mg), and Cu(OAc)2 (1.8 mg, 0.01 mmol). The reaction mixture was stirred under air at 50°C for 2 h and then at 90°C for 3 h. The reaction mixture was extracted with ether and the organic phase was washed with brine and then dried over MgS04. After evaporation of the solvent the residue was subjected to flash chromatography giving the corresponding pyridine. 

A simple, modular synthesis of polysubstituted pyridines of type 180 involves Cu-catalyzed cross-coupling of alkenylboronic acids with a,P-unsaturated ketoxime-N-pentafluorobenzoates 179 followed by cyclization and air oxidation [128] ... 

A. Dimerization of two molecules of ketoxime with abstraction of hydroxyl-amine (analog of crotonic condensation) to afford oxime of a,p-unsaturated ketoxime (Scheme 1.152)... 

SCHEME 1.152 Possible formation of a,p-unsaturated ketoxime from acetoxime. 

This reaction was first reported by Semmler in 1892 and subsequently studied by Wolff in 1902 and Schroeter in 1911. It is the rearrangement of an oxime of an a,p unsaturated cyclohexenone (or known as the o, )0-unsaturated cyclohexenyl ketoxime) to an aromatic amine in a mixture of acetic anhydride and acetic acid saturated with HCl or HBr. Therefore, this reaction is generally known as the Semmler-Wolff aromatization," Semmler-Wolff rearrangement, or Semmler-Wolff reaction. Occasionally, it is also referred to as the Semmler-Wolff-Schroeter reaction. It should be pointed out that the Beckmann Rearrangement,and the fragmentation to nitriles often compete with the Semmler-Wolff aromatization. In addition, the Semmler-Wolff aromatization is obstructed by the substituents close to the reaction center. ... 

The photochemical cyclisation of p.y-unsaturated ketoximes to 2-isoxazolines, e.g., 16—>17, has been reported <95RTC514>. 2-Isoxazolines are obtained from alkenes and primary nitroalkanes in the presence of ammonium cerium nitrate and formic acid <95MI399>. Treatment of certain 1,3-diketones with a nitrating mixture generates acyl nitrile oxides, which can be trapped in situ as dipolar cycloadducts (see Scheme 3) <96SC3401>. 

Further details of phase-transfer addition of dibromocarbene to a,(3-unsaturated esters and ketones [e.g. (18)] and subsequent reductive monode-bromination with tributyltin hydride (Vol. 7, p. 34) have been publishedJulia reports the use of solid NaOH-Et3NCH2Ph CP for the solid-liquid phase-transfer catalytic generation of dichlorocarbene (addition to a-pinene and limonene). Dichlorocarbene also provides a mild and efficient method for the Beckmann fragmentation of anh-a-hydroxy-ketoximes into aldehydes (or ketones) and nitriles [e.g. 2-exo-hydroxy-3-hydroxyiminobornane into (24 X = CHO, Y = CN)]. Trimethylsilylcyclopropanes are synthesized by adding the... 

Catalytic enantioselective iodoetherification of l-aryl-P,Y-unsaturated ketoximes such as 41 was accomplished using N-iodosuccinimide (MS) as electrophilic iodine source, catalytic I2, and the bifunctional oi anocatalyst 42. The corresponding 3-aryl A -isoxazohnes containing a quaternary stereocenter at C-5 were obtained with high yield and enantioselectivity (13AGE8450). 

With the help of a bifiinctional thiourea catalyst 55, Mukherjee and coworkers contemporaneously developed a related catalytic asymmetric iodoetherification of oximes (Scheme 2.31). A variety of p.y-unsaturated ketoximes were cyclized using commercially available A-iodosuccinimide (NIS) as the iodine source and iodine as the cocatalyst to furnish A -isoxazolines containing a quaternary stereogenic center in high yields and good to excellent enantioselectivities [47]. Besides, the oxime iodoetherification products could be subjected to a number of synthetically useful transformations to produce other important organic compounds. 

---