Meyers oxazoline coupling

The first asymmetric intermolecular synthesis of 0-methylancistrocladine (2) involved the use of a Meyers biaryl coupling, successfully utilised in the earlier synthesis of dehydroancistrocladine (66), to construct the biaryl linkage atropisomer-selectively (ref. 60,61). It was envisaged that 2 could arise from the acetamide 102 which in turn could be derived from biaryl 103 (Scheme 14). A coupling between the Grignard reagent 104 and chiral oxazoline 105 could then provide 103 stereospecifically. This approach required the synthesis of chiral oxazoline 105 which is outlined in Scheme 15 and begins with the nitrile 71 available in three steps from 1,5-diacetoxynaphthalene (see Scheme 8). 

Meyers has also reported the use of chiral oxazolines in asymmetric copper-catalyzed Ullmann coupling reactions. For example, treatment of bromooxazoline 50 with activated copper powder in refluxing DMF afforded binaphthyl oxazoline 51 as a 93 7 mixture of atropisomers diastereomerically pure material was obtained in 57% yield after a single recrystallization. Reductive cleavage of the oxazoline groups as described above afforded diol 52 in 88% yield. This methodology has also been applied to the synthesis of biaryl derivatives. 

Discussions of oxazolines as chiral directing groups are included in the previous sections under the appropriate reaction classifications. Meyers has already published a recent review of chiral oxazolines (1998) that focused primarily on their use in aromatic reactions and Ullmann coupling reactions in particular. The examples of oxazolines as chiral directing groups described in this section will include reactions that are not discussed in any previous section of this chapter. 

Achiral 2-stannyloxazolines are known to undergo Shlle coupling with aromahc halides. However, Stille couplings with chiral 2-halooxazolines were not reported until Meyers and Novachek prepared the requisite 2-bromooxazoline 365 (see Scheme 8.116) and successfully coupled 365 with a variety of alkynyl and alkenylstannanes to afford chiral 2-substituted oxazolines 635 in reasonable yields (Scheme 8.200). ... 

By using this method, 4-methyl-2 -cyanobiphenyl, an important intermediate for the synthesis of the antihypertensive drug Losartan, can be easily prepared.132 2-(t>-Chlorophenyl)-oxazoline reacts with excess of arylmagnesium halide without catalysis, as it was shown by Meyers for 2-(o-methoxyphenyl)-oxazolines.133 Cobalt(ll) salts catalyze the coupling of Grignard reagents with a-chloroazines at —40°C in ether (Scheme 47).134 135... 

New syntheses of ( )-ar-turmerone (79) and ( )-nuciferal (80) have been reported (Schemes 10 and 11 ) whereas Meyers and Smith have used the (+)-oxazoline (81) to good effect in an asymmetrically induced synthesis of (+)-ar-turmerone (82) (Scheme 12). A neat one-pot synthesis of /3-curcumene (83) has been developed which involves only two steps (Scheme 13). In a synthesis of the aromatic analogue, (-)-a-curcumene (84), Kumada et al. have used an asymmetrically induced cross-coupling Grignard reaction in the presence of a nickel complex of (85) to produce (84) in 66% enantiomeric excess (Scheme 14). A Vilsmeier-Haack-Arnold formylation of (-f-)-limonene has been used as... 

Meyers et al. have reported an asymmetric synthesis of (-)-steganone (179) in which formation of the biaryl bond represents the first stage in the synthesis of the eight membered ring (scheme 69) [155]. They have also used their oxazoline-mediated coupling approach to carry out asymmetric syntheses of (-)-schizandrin and (-)-isoschizandrin [156]. 

Meyers and colleagues described the palladium-catalyzed carbonylative synthesis of oxazolines as early as 1992 [268]. Aryl or enol triflates made from the corresponding ketones and phenols, and also aryl halides, were used as starting materials and coupled with amino alcohols to give chiral a,)S-unsaturated or aryl oxazolines in good yields. Later on, Perry s group performed systematic studies on this one-pot, two-step process for the preparation of oxazolines (Scheme 2.37) [269, 270]. 

Meyers, A.I., Robichaud, A.], and McKermon, M.J. (1992) The synthesis of chiral a,P-unsaturated and aryl oxazolines from ketones and arols via their triflates and Pd-catalyzed CO and amino alcohol coupling. Tetrahedron Letters, 33, 1181—... 

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