Applications endo-selective

The TiX2-TADD0Late-catalyzed 1,3-dipolar q cloaddition reactions were extended to include an acrylate derivative [66]. In the absence of a catalyst, the reaction between nitrones 1 and acryloyl oxazolidinone 19b proceeded to give a mixture all eight regio-and stereoisomers (Scheme 6.23). However, application of in this case only 10 mol% of Ti(OTs)2-TADDOLate 23d as catalyst for the reaction of various nitrones 1 with alkene 19b, led to complete regioselectivity and high endo selectivity in the reaction and the endo products 21 were obtained with 48-70% ee (Scheme 6.23) [66]. 

In 1997 the application of two different chiral ytterbium catalysts, 55 and 56 for the 1,3-dipolar cycloaddition reaction was reported almost simultaneously by two independent research groups [82, 83], In both works it was observed that the achiral Yb(OTf)3 and Sc(OTf)3 salts catalyze the 1,3-dipolar cycloaddition between nitrones 1 and alkenoyloxazolidinones 19 with endo selectivity. In the first study 20 mol% of the Yb(OTf)2-pyridine-bisoxazoline complex 55 was applied as the catalyst for reactions of a number of derivatives of 1 and 19. The reactions led to endo-selective 1,3-dipolar cycloadditions giving products with enantioselectivities of up to 73% ee (Scheme 6.38) [82]. In the other report Kobayashi et al. described a... 

Sudo and Saigo153 reported the application of ds-2-amino-3,3-dimethyl-l-indanol derived l,3-oxazolidin-2-one 231 as a chiral auxiliary in asymmetric Diels-Alder reactions. The TV-crotonyl and TV-acryloyl derivatives were reacted with cyclopentadiene, 1,3-cyclohexadiene, isoprene and 2,3-dimethyl-l,3-butadiene, using diethylaluminum chloride as the Lewis acid catalyst. The reactions afforded the expected cycloadducts in moderate to high yields (33-97%) with high endo selectivities and high de values (92% to >98%). 

The above described reaction has been extended to the application of the AlMe-BINOL catalyst to reactions of acyclic nitrones. A series chiral AlMe-3,3 -diaryl-BINOL complexes llb-f was investigated as catalysts for the 1,3-dipolar cycloaddition reaction between the cyclic nitrone 14a and ethyl vinyl ether 8a [34], Surprisingly, these catalysts were not sufficiently selective for the reactions of cyclic nitrones with ethyl vinyl ether. Use of the tetramethoxy-substituted derivative llg as the catalyst for the reaction significantly improved the results (Scheme 6.14). In the presence of 10 mol% llg the reaction proceeded in a mixture of CH2CI2 and petroleum ether to give the product 15a in 79% isolated yield. The diastereoselectiv-ity was the same as in the acyclic case giving an excellent ratio of exo-15a and endo-15a of >95 <5, and exo-15a was obtained with up to 82% ee. 

It has been more difficult to obtain the exo isomer in the above described reaction. Application of the TiCl2-TADDOLate complex induced fair exo selectivity and up to 60% ee. This was improved by the application of succinimide as an auxiliary for the alkene. This approach has been the only entry to a highly exo selective reaction and up to 72% ee of the exo isomer was obtained. In the Pd(BF4)2-BI-NAP-catalyzed reaction which gave mixtures of the endo and exo isomers, high ee of up to 93% was in a single case obtained for the minor exo isomer. In one case it was also observed that a Zn(OTf)2-BOX complex induced some exo selectivity and up to 82% ee of the exo isomer. 

Apart from the cyclopropanation reaction, only one example has been published of the application of ionic liquids as reaction media for enantio-selective catalysis with bis(oxazoline) ligands. In this case, the complex 6b-ZnCl2 was used as a catalyst for the Diels-Alder reaction between cyclopen-tadiene and N-crotonyloxazolidin-2-one in dibutyUmidazoUiun tetrafluorob-orate (Scheme 9) [48]. Compared with the same process in CH2CI2, the reaction was faster and both the endofexo selectivity and the enantioselectivity in the endo product were excellent. However, experiments aimed at recovering the catalysts were not carried out. 

Enders et al. (96) recently described the application of the chiral azomethine precursor 61 (Scheme 12.21). The azomethine ylide was formed in situ by heating with different benzaldehydes. The reactions of four different azomethine ylides with A-phenyl maleimide led to the formation of endo-62 and exo-62 in ratios of 2 1 in very high yields. The diastereofacial selectivity was estimated to be >96% de for both products, since no other diastereomers were observed by proton nuclear magnetic resonance ( H NMR) spectroscopy. 

Mukai et al. (36,37) applied the chiral tricarbonyl(r 6-arene)chromium(0)-derived nitrone 24b in 1,3-dipolar cycloadditions with various alkenes, such as styrene 25 (Scheme 12.11). The analogous nonmetallic nitrone 24a was used in a reference reaction with 25, giving the isoxazolidine 26a with an endo/exo ratio of 82 18. By the application of nitrone 24b in the 1,3-dipolar cycloaddition with 25, the endo/exo-selectivity changed significantly to give exo-26b as the only observable product. The tricarbonylchromium moiety effectively shielded one face of the nitrone, leading to high diastereofacial selectivity. The product exo-26b was obtained with 96-98% de. 

Selective alkylation of the enamidic nitrogen in 159 with 2-iodo-4,5-methylenedioxybenzyl bromide afforded the enamino-enamide 160 (Scheme 23). Application of Heck s oxidative coupling method to 160, generated by 6-endo addition, the tetracydic enamide... 

The addition of diorganozinc reagents to a-alkoxyaldehydes furnishes selectively protected 1,2-diols.19 Applications toward the synthesis of pheromones like (-)-exo- and (-)-endo-brevicomin 2 and 3 exploits the catalytic nature of the stereochemical induction, e.g. the newly formed chiral centre depends only on the configuration of the chiral catalyst 1. 

In a parallel study, it was found that chelating chiral diamines 208 or 209 are well suited as ligands to promote Kumada-type couplings of primary and secondary alkyl halides 202 with aryl Grignard reagents 203 (entry 4) [281]. This reaction was applicable to alkyl bromides and alkyl iodides, while alkyl chlorides gave only low yields. Acetal and ester functions are tolerated. A notable feature is the stereoretentive arylation of fra s-a-bromo acetals with excellent diastereo-selectivity. The involvement of radicals is supported by the stereoconvergent formation of cxo-phenvI norbornane from both endo- or exo-bromonorbomane (cf. Part 1, Fig. 9) and radical 5-exo cyclizations (see below). 

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