Ortho-Arylated oxazolines

Scheme 9.27 Selective ruthenium-catalyzed ortho-arylation of the oxazoline 76 with the aryl...

Ortho-aryhted oxazolines 161 were prepared through Cr(II)-catalyzed oxidative arylation of 2-TMS-phenyloxazoline 160 with aromatic Grignard reagents in the presence of 2,3-dichlorobutane (DCB). The TMS group could be converted into a second ortho-axy substituent (14OL5208). 

More importantly it was found that the ketimines could be more easily diarylated in water in basic medium (K2CO3) than in NMP using the Ru(II)/2KOAc/l PPh3 catalytic system [(Eq. 20a)] [85]. As ketones do not direct ortho C-H bond activation followed by arylation, this arylation of aldimines and ketimes can be used for the access to diarylated aldehydes and ketones that are thus obtained by acidification of their aqueous solution. Oxazoline can also efficiently direct ortho-arylation of aryl groups [(Eq. 20b)] [85]. 

These reactions complement recently developed palladium(0)amination reactions [146,147,148] and related procedures using a copper(I) [149] - or ni-ckel(O) [151] - catalysis. As indicated above, the mild reaction conditions are compatible with a range of functional groups. Functionalized arylmagnesium chlorides such as 309 prepared by an I/Mg-exchange readily undergo addition reactions to aryl oxazolines. The addition-elimination of 309 to the -methoxy aryloxa-zoline followed by an ortHo-lithiation and substitution with ethylene oxide leads to a polyfunctionalized aromatic intermediate 310 for alkaloid synthesis (Scheme 4.68) [165]. 

Bolm et al. (130) reported the asymmetric Baeyer-Villiger reaction catalyzed by Cu(II) complexes. Aerobic oxidation of racemic cyclic ketones in the presence of pivalaldehyde effects a kinetic resolution to afford lactones in moderate enan-tioselectivity. Aryloxide oxazolines are the most effective ligands among those examined. Sterically demanding substituents ortho to the phenoxide are necessary for high yields. Several neutral bis(oxazolines) provide poor selectivities and yields in this reaction. Cycloheptanones and cyclohexanones lacking an aryl group on the a carbon do not react under these conditions. 

Djafri et al. have determined by DNMR the barriers to rotation of aryl groups (unsubstituted in the ortho positions) in position 3 of 4,5-dimethyl-oxazoline-2-thiones (53), -imidazoline-2-thiones (54), and -thiazo-line-2-thiones (55) (85JCS(P2)273) the barriers were 38.9, 51.5, and 74.0 kJ mol respectively. They conclude that the ring element X (O, NCH3, S) affects the barriers mainly by its influence on the geometry of the ring. 

The arylation of secondary phosphines 201 with ortho-aiy iodides, catalyzed by generated in situ complex Pda (dba>3 x CHQ3, containing chiral ligand Et,Et-FerroTANE 207 and LiBr, led to the formatiOTi of corresponding tertiary phosphines with enantioselectivity of 90% cc [ 132,137]. The palladium complex 209 also showed high enantioselectivity in arylation of secondary phosphines [131,132]. Some examples of arylation reaction of secondary phosphines with low ee were described. The asymmetric arylation of phosphine boranes with anisyl iodide, catalyzed by chiral complex of oxazoline phosphine 208, led to the formation of enantiomerically enriched tertiary phosphines 206 with 45% ee [134]. The Pd complex 210 of (R )-t-Bu-JOSlPHOS ligand catalyzed arylation of PH(Me)(Ph)(BH3) by o-anisyl iodide with the formation of PAMP-BH3 with 10% ee (Table 3) [112]. 

As carboxylic acid additives increased the efficiency of palladium catalysts in direct arylations through a cooperative deprotonation/metallation mechanism (see Chapter 11) [45], their application to ruthenium catalysis was tested. Thus, it was found that a ruthenium complex modified with carboxylic acid MesC02H (96) displayed a broad scope and allowed for the efficient directed arylation of triazoles, pyridines, pyrazoles or oxazolines [44, 46). With respect to the electrophile, aryl bromides, chlorides and tosylates, including ortho-substituted derivatives, were found to be viable substrates. It should be noted here that these direct arylations could be performed at a lower reaction temperatures of 80 °C (Scheme 9.34). 

Besides pyridine, several DGs have been used, such as pyrtizole, oxazoline, and imines, and so on, for the diarylation of aryl substrates in the ortho-position [lej. 

Oxazoline was shown to be an efficient directing group for arylation of arene derivatives with Ru(II) catalyst [(Eq. 5)] [61], A -Acylimidazole was also shown to be a directing group promoting ortho monoarylation of arene. Ort/io-alkenylation of 2-phenyl oxazoline with alkenylbromide was performed using the same mthe-nium(II) catalyst [61]. 

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