3- Alkenoyl-oxazolidinones

Due to the presence of an electron-withdrawing group on the dipolarophile, these processes are classified as type 1 reactions. The process involves the transference of charge from the dipole to the dipolarophile. When catalyzed by metallic compounds, coordination of the dipolarophile is highly desired. Usually, coordination of a nitrone to the Lewis acid is more feasible than coordination of a carbonyl compound. For this reason, alkenes that enable a bidentate coordination to the Lewis acid, such as 3-alkenoyl-oxazolidinones (Scheme 5), have been frequently employed as a model system to smdy the metal-catalyzed 1,3-dipolar cycloaddition... 

One of the problems related to the LA induced activation of a,p-unsaturated carbonyl compounds for the reaction with a nitrone is the competitive coordination of the nitrone and the a,(3-unsaturated carbonyl compound to the Lewis acid (Scheme 12.65). Calculations have shown that coordination of the nitrone to the LA is more feasible than a monodentate coordination of a carbonyl compound. However, this problem can be circumvented by the application of alkenes such as 3-alkenoyl-oxazolidinones, enabling abidentate coordination to the LA, which is favored over the monodentate coordination to the nitrone. 

In 2004, Nishiyama and Iwasa reported that a chiral Lewis acid complex, generated from Mn(C104)2 and the chiral xabox ligand 12, could be used as an efficient catalyst for the asymmetric 1,3-DC reactions of nitrones 9 with 3-alkenoyl oxazolidinone 10 [12]. These reactions were typically carried out at room temperature and provided the corresponding isoxazolidines 11 in good to excellent stereoselectivities (Scheme 2.5). 

Several chiral Ti(IV) complexes are efficient catalysts and have been applied to numerous reactions, especially in combination with the TADDOL 244 ligands (350). Chiral TiCl2-TADDOLates were the first asymmetric catalysts to be applied in the normal electron-demand 1,3-dipolar cycloaddition of nitrones 225 with alkenoyl-oxazolidinones 241 (Scheme 12.73) (351). These substrates have turned... 

The application of two different chiral ytterbium catalysts 263 and 264 for the 1,3-dipolar cycloaddition was reported almost simultaneously by two independent research groups in 1997 (372,373). In both reports, it was observed that the achiral Yb(OTf)3 and Sc(OTf)3 salts catalyze the 1,3-dipolar cycloaddition between nitrones 225 and alkenoyl oxazolidinones 241 with endo-selectivity (Scheme 12.84). In the first study, 20 mol% of the Yb(OTf)2-pyridine-bis(oxazo-line) complex 263 was used as the catalyst for reactions of several derivatives of... 

Zinc-trifiate complexes with a series of chiral bis(oxazoline) ligands, differing in the length of the chain connecting the chiral oxazoline subvmits and in the nature of the substituent at the chiral center, catalyze the reaction of A(-crotonyloxazolidinone with cyclopentadiene (320). Cycloaddition reactions of alkenoyl-oxazolidinones with both cyclopentadiene and diphenyl nitrone take place with up to 86% ee (321). 

In most TiCl2-TADDOLate-catalyzed Diels-Alder and 1,3-dipolar cycloaddition reactions oxazolidinone derivatives are applied as auxiliaries for the alkenoyl moiety in order to obtain the favorable bidentate coordination of the substrate to the catalyst... 

No single examples have been reported so far for the catalyzed asymmetric diazoalkane cydoadditions. Based on the kinetic data on the relative reaction rates observed by Huisgen in the competitive diazomethane cydoadditions between 1-alkene and acrylic ester (Scheme 7.32), it is found that diazomethane is most nu-deophilic of all the 1,3-dipoles examined (kaciyiate/fci-aikene = 250000) [78]. Accordingly, the cydoadditions of diazoalkanes to electron-defident alkenes must be most efficient when catalyzed by a Lewis acid catalyst. The author s group has become aware of this possibility and started to study the catalyzed enantioselective diazoalkane cydoadditions of 3-(2-alkenoyl)-2-oxazolidinones. 

Finally we have performed the Michael addition reactions of malononitrile and 3-(2-alkenoyl)-2-oxazolidinones in dichloromethane in the presence of the R,R-DBF0X/Ph-Ni(C104)2-31 20 and TMP (10 mol% each). Enantioselectivities were a little lower than 90% ee for acceptors having a variety of / -substituents. The best selectivity was 94% ee in the reaction of t-butyl-substituted acceptor (Scheme 7.50). 

Kanemasa et al.63 reported that cationic aqua complexes prepared from the /ram-chelating tridentate ligand (i ,f )-dibenzofuran-4,6-diyl-2,2,-Mv(4-phcnyloxazolinc) (DBFOX/Ph) and various metal(II) perchlorates are effective catalysts that induce absolute chiral control in the Diels-Alder reactions of 3-alkenoyl-2-oxazolidinone dienophiles (Eq. 12.20). The nickel(II), cobalt(II), copper(II), and zinc(II) complexes are effective in the presence of six equivalents of water for cobalt and nickel and three equivalents of water for copper and zinc. 

Alkyl- or 3-aryl-2,4-oxazolidinediones via photochemical cyclization, ° organonickel-mediated carbonylation, ° cyclization of A-alkenyl-a-acet-amides, ° carboxylation and cyclization of 2-propynamides, °" cyclization of (9-carbamates of a-hydroxy acetic acids and esters,cyclization of a-hydroxy acetamides,and catalytic asymmetric dihydroxylation (ADH) of A-alkenoyl-2-oxazolidinones. ... 

The first effective enantioselective 1,3-dipolar cycloaddition of diazoalkanes catalyzed by chiral Lewis acids was reported in the year 2000 (139). Under catalysis using zinc or magnesium complexes and the chiral ligand (/ ,/ )-DBFOX/Ph, the reaction of diazo(trimethylsilyl)methane with 3-alkenoyl-2-oxazolidin-2-one 75 (R2 = H) gave the desilylated A2-pyrazolines (4S,5R)-76 (R =Me 87% yield, 99% ee at —40°C) (Scheme 8.18). Simple replacement of the oxazolidinone with the 4,4-dimethyloxazolidinone ring resulted in the formation of (4/ ,5S)-77 (R1 = Me 75% yield, 97% ee at -78 °C). 

Yamamoto and co-workers (135,135-137) recently reported a new method for stereocontrol in nitrile oxide cycloadditions. Metal ion-catalyzed diastereoselective asymmetric reactions using chiral electron-deficient dipolarophiles have remained unreported except for reactions using a-methylene-p-hydroxy esters, which were described in Section 11.2.2.6. Although synthetically very useful and, hence, attractive as an entry to the asymmetric synthesis of 2-isoxazolines, the application of Lewis acid catalysis to nitrile oxide cycloadditions with Achiral 3-(2-alkenoyl)-2-oxazolidinones has been unsuccessful, even when > 1 equiv of Lewis acids are employed. However, as shown in the Scheme 11.37, diastereoselectivities in favor of the ft-cycloadducts are improved (diastereomer ratio = 96 4) when the reactions are performed in dichloromethane in the presence of 1 equiv of MgBr2 at higher than normal concentrations (0.25 vs 0.083 M) (140). The Lewis acid... 

Vinylogous Mukaiyama-Michael additions of 2-trimethylsilyloxyfuran to 3-alkenoyl-2-oxazolidinones to provide 7-butenolides were shown to be /7-selective. The reaction could be rendered enantioselective in the presence of a (T symmetric copper-bisoxazoline complex <1997T17015, 1997SL568> or a l,T-binaphthyl-2,2 -diamine-nickel(ii) complex as catalyst, as depicted in Equation (16) <2004CC1414>. 

R,R)-4,6-Dibenzofiirandiyl-2,2 -bis(4-phenyloxazoline), DBFOX/Ph (5), is a novel tridentate bisoxazoline ligand developed by Kanemasa and coworkers that has been successfully used as a chiral Lewis acid in enantioselective Diels-Alder-reactions, nitrone cycloadditions and conjugate additions of radicals and thiols to 3-(2-alkenoyl)-2-oxazolidinones. Representative examples for cycloadditions using the Ni(C104)2-6H20 derived complex are shown below. 

Reports on the advances of asymmetric 1,3-dipolar cycloadditions include the reaction of diazoalkanes to 7V-(2-alkenoyl)oxazolidin-2-ones catalyzed by Mg or Zn complexes of 73, showing cooperative chiral control by the achiral oxazolidinone auxiliary and the chiral ligand.An intramolecular cycloaddition of the same kind from substrates containing a chiral cyclic AiA -dimethylaminal unit adjacent to the dipolarophilic double bond (i.e., 74) proves very successful in the asymmetric sense, although the reaction of an analogous nitrone lacks stereoselectivity. 

Kanemasa, S., Oderatoshi, Y. and Wada, E. (1999) Asymmetric conjugate addition ofthiols to a 3-(2-alkenoyl)-2-oxazolidinone catalysed by the DBFOX/Ph aqua complex of nickel(II) perchlorate. Journal of the American Chemical Society, 121, 8675-8676. 

In addition, they carried out enantioselective Michael-type hydroamination of the alkenoyl-A-oxazolidinone 26 with aniline and obtained the chiral amine 27 with 93 % ee. Furthermore, they reported hydroamination of dihydrofuran (28) and 2,3-dihydropyran (30). Reaction of dihydrofioran (28) with morpholine proceeded at room temperature to give 2-aminotetrahydrofuran 29 regioselectively in high yield. Hydroamination of 2,3-dihydropyran (30) with morpholine proceeded at 80 "C to give 2-morpholinotetrahydropyran (31). For this hydroamination, phosphine-free... 

Kanemasa e t al. had found that Ni( 11) and F e (11) chiral complexes derived from 4,6-dibenzofurandiyl-2,2 -bis(4-phenyloxazoline)-Ph ligand act as chiral Lewis acids to make isoxazolidines through nitrone cycloadditions reactions. Strong binding of nitrones to catalysts is a serious problem in the Lewis acid catalyzed nitrone cycloadditions, and therefore, bidentate dipolarophile such as 3-(2-alkenoyl)-2-oxazolidinones have been mostly used to protect the tight coordination of acceptors to the catalysts. Recently, they reported that Ni(II), Zn(II), Mg(II), and Co(II) complexes with (R,R)-DBFOX-Ph ligand catalyzed enantioselective nitrone reactions to a variety of... 

A novel chiral hafnium catalyst, which was readily prepared fromHf(OTf)4 and a proline-derived chiral ligand, has been tested in asymmetric Michael reactions of thiols with 3-(2-alkenoyl)-2-oxazolidinones, affording the corresponding adducts in high yield and enantioselectivity. Although chiral Lewis acids are less reactive than the original Lewis acids in many cases, ligand acceleration has been demonstrated in this as)unmetric Michael addition reaction (eq 18). ... 

Recently, Suga et al. demonstrated that BINIM-Ni(II) catalysts are also effective in affording high levels of asymmetric induction (up to 97% ee) for 1,3-dipolar cycloaddition reactions between ethyl diazoacetate and 3-acryloyl-2-oxa-zolidinone or 2- (2-alkenoyl)-3-pyrazolidinone derivatives in the selective formation of 2-pyrazolines having a methine carbon substituted to the coordination auxiliary groups [27]. The cycloadditions of 3-acryloyl-2-oxazolidinone and its... 

SCHEME 7.28 Asymmetric cycloaddition reactions of 2-benzopyrylium-4-olates with 3-(2-alkenoyl)-2-oxazolidinones catalyzed by (4S,5S)-PyBOX-4,5-Ph2-Yb(in) complex. 

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