5-monosubstituted oxazolines

Michael Reaction. 5(47/)-Oxazolones undergo base-catalyzed conjugate addition to activated unsaturated compounds to afford the corresponding C-4 Michael adducts. For example, base-catalyzed addition of a 4-monosubstituted-5(4//)-oxazolone 157 to methyl propiolate yields a mixture of diastereomeric methyl 3-(5-oxo-2-phenyl-2-oxazolin-4-yl)acrylates 158. Hydrolytic ring opening of 158 and subsequent oxidation with lead tetraacetate affords 3-acylacrylates 160... 

Epoxides also undergo the Ritter reaction in good yields with retention of configuration via a episulfonium intermediate 190a (double-inversion process). For monosubstituted epoxides, the yields of oxazolines are lower due to nondis-criminatory attack of the nitrile on both the primary and the secondary carbon atom of the episulfonium intermediate. Complete retention of configuration is still observed despite the lower yield (Scheme 8.54). 

Cyclizations of urea derivatives of allylamines with selenium reagents have been examined recently (equation 62 and Table 18).98 Cyclization of the allylic ureas produces franj-2-oxazoline derivatives with high stereoselectivity when the double bond is internal (Table 18, entry 2). Although O-methylisourea derivatives can be cyclized to dihydroimidazoles [see Section 1.9.3.2.2(ii)], cyclization with phenylsel-enenyl trifluoromethanesulfonate and trifluoromethanesulfonic acid produces 5,6-dihydro-1,3-oxazines (6-endo products), even when the double bond is monosubstituted (entry 3). 

The C2-symmetric 2,6-bis(2-oxazolin-2-yl)pyridine (pybox) ligand was originally applied with Rh for enantioselective hydrosilylation of ketones [79], but Nishiyama, Itoh, and co-workers have used the chiral pybox ligands with Ru(II) as an effective cyclopropanation catalyst 31 [80]. The advantages in the use of this catalyst are the high enantiocontrol in product formation (>95 % ee) and the exceptional diastereocontrol for production of the trans-cyclopropane isomer (>92 8) in reactions of diazoacetates with monosubstituted olefins. Electronic influences from 4-substituents of pyridine in 31 affect relative reactivity (p = +1.53) and enantioselectivity, but not diastereoselectivity [81]. The disadvantage in the use of these catalysts, at least for synthetic purposes, is their sluggish reactivity. In fact, the stability of the intermediate metal carbene has allowed their isolation in two cases [82]. 

More recently, Pfaltz has reported high enantioselectivities for the cyclopropanation of monosubstituted alkenes and dienes with diazo carbonyl compounds using chiral (semicorrinato)copper complexes (P-Cu) (23-25), and Evans, Masamune, and Pfaltz subsequently discovered exceptional enantioselectivities in intermolecular cyclopropanation reactions with the analogous bis-oxazoline copper complexes (26-28). With the exception of the chiral (camphorquinone dioximato)cobalt(II) catalysts (N-Co) reported by Nakamura and coworkers (29,30), whose reactivities and selectivities differ considerably from copper catalysts, chiral complexes of metals other than copper have not exhibited similar promise for high optical yields in cyclopropanation reactions (37). 

The Evans copper(ll) bis-oxazoline (BOX) catalysts (7.193) and (7.194) (see Section 7.1) have also been used effectively for glyoxalate ene reactions. Even monosubstituted alkenes can be used as the ene component, where the alkene (7.195) reacts with ethyl glyoxalate (7.196) to give the a-hydroxy ester (7.197) with very high enantioselectivity. Other alkenes were also effective, providing enantiomeric excesses of over 90%, including alkene (7.198), which is converted into the ene-product (7.199). 

Yang developed a Pd(II)-catalyzed enantioselective oxidative domino cycUzation reaction with the chiral ligand 166 comprising quinoline and oxazoline under molecular oxygen as a green oxidant [56]. While the use of (—)-sparteine as a ligand provided good enantioselectivities in the case of oxidative domino cycHzation of monosubstituted olefinic substrates 167 (R = = H) [57], its use for the reaction... 

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