Chiral bisoxazoline ligand

Undoubted, 2-haloaniline derivatives still maintain most vored precursor status for the preparation of the indole nucleus. Larock now reports the frill details of his examination of the asymmetric addition of IV-tosyl-2-iodoaniline (63) to allenes 64 (e.g. 1,2-undecadadiene) in the presence of palladium catafysts and chiral bisoxazoline ligand to afford chiral indolines 65 in up to 88% ee <99JOC7312>. Cook has utilized the palladhjm-catafyzed heteroannulation of iodoanilines with alkynes derivatized with the Schollkopf chiral auxiliary as a reliable route to optically active ring-A substituted tryptophans <99TL657>. 

Several Lewis acids were investigated in enantioselective radical additions to cinnamoyl oxazolidone 59 using chiral bisoxazoline ligand. With Fe(NTf2)2 and fBu-BOX ligands, up to 80% ee were achieved (Scheme 8.26) [86], Selectivities up to 98% were obtained when Mg(NTf2)2 was used as the precatalyst. 

Heterocyclic products such as indolizidines and quinolizidine (Scheme 9.7) could also be obtained, as was shown by Takacs et al. for the synthesis of 5 in a stereoselective fashion applying a chiral bisoxazoline ligand [18]. The product was obtained in 65% yield with excellent diastereoselectivity and the enol ether was formed exclusively as the E-isomer. 

In addition to these commonplace substrates, only a few extraordinary educts have been used in iron-catalyzed DA reactions, such as the naphthoquinones investigated by Brimble and McEwen [75]. Whereas the application of FeCl3 and a chiral bisoxazoline ligand gave only a 25% yield and no chiral induction in the reaction of 2-acetyl-l,4-naphthoquinone with cyclopentadiene, the corresponding copper(II) triflate gave a 66% yield and moderate enantioselectivities (up to 50% ee). Another example was reported by Shibasaki s group in which the 2-alkoxy-l,3-butadiene 40... 

In this case a chiral bisoxazoline ligand was used S. Kanemasa, K. Adachi, H. Yamamoto, E. Wada, Bull. Chem. Soc.Jpn. 2000, 73, 681. 

Aryl iodides 590 react with nona-1,2-diene in the presence of a palladium catalyst and a chiral bisoxazoline ligand to afford isochromans 591 in good yield with moderate enantioselectivity (Equation 244) <1999JOC7312>. 

A palladium-catalyzed asymmetric annulation of the allene 1133 with 2-iodobenzoic acids proceeds in the presence of a chiral bisoxazoline ligand to afford 4-methylenedihydroisocoumarins in good yield and enantiomeric excess (Equation 440) <1999JOC7312>. 

Diastereotopic differentiation of two leaving groups has been achieved for the first time by the reaction of (dichloromethyl)borates with BuLi in the presence of Yb(OTf)3 and the chiral bisoxazoline ligand 203.108 As shown in Figure 51, pinacol dichloromethyl boronate (204) gave 205 in up to 88% ee. The reaction can be said to be catalytic, as the use of 0.5 equiv. of chiral ligand 203 and 0.2 equiv. of Yb(OTf )3 provided 205 in 55% ee and 86% yield. 

Highly diastereoselective alkyl radical addition to Oppolzer s camphorsultam derivative (33) of oxime provides enantiomerically pure a-alkyl-a-amino acid derivative (34) at — 78 °C by the same method as shown in eq. 10.16. Moreover, enantioselective tandem radical 1,2-difunctionalization of cinnamamide (35) can be carried out with high stereoselectivity, using the chelation manner of the cinnamamide and a chiral bisoxazoline ligand on Mgl2, as shown in eq. 10.17. 

Chiral bisoxazoline ligands were initially chosen for these experiments (Eq. (13.52)). It was found that simple bisoxazoline ligands 167 derived from amino acids led to good yields but moderate selectivities of products 168 when catalytic amounts of chiral Lewis acid were used (67% ee with 20 mol % of the catalyst and 86% chemical yield). 

Miura and coworkers showed that the reaction could also be carried out using catalytic amounts of Cul in the presence of pyridine (95JOC4999). Asymmetric reactions were reported to occur with chiral bisoxazoline ligands producing p-lactams with moderate (40-68%) enantiomeric excesses. Use of an oxazolidinone with a chiral auxiliary appended to the alkyne also provided enantiomerically pure products (02TL5499). In all of these latter reports, mixtures of cis and irons lactam isomers were obtained in which the trans-product predominates. It was also shown that the c/s-isomer could easily be converted to the trans-product when exposed to base. 

The use of a chiral bisoxazoline ligand 109 for the enantioselective palladium-catalyzed annelation of allenes has been reported by Larock and Zenner (an example is given in Scheme 32) [82]. Even though the alkene insertion step here is followed by an intramolecular nucleophihc attack of the amine functionality... 

The Evans system employs chiral bisoxazoline ligands with copper(I) triflate. Exceptionally high levels of enantioselection were observed in the aziridination of cinnamate ester derivatives (Scheme 8),but thus far no other substrate classes have been demonstrated to undergo aziridination with synthetically-useful levels of stereoinduction. 

Enantioselective oxycarboration of allenes with oxygen-functionalized aryl and vinyl halides to give oxygen heterocycles has been achieved with Pd(OAc)2 or Pd(dba)2 in the presence of a chiral bisoxazoline ligand with up to 78% yield and 79% ee94. 

Analogous conversion of 2-iodoaniIines with allenes in the presence of Pd(OAc)2 or Pd(dba)2 and a chiral bisoxazoline ligand leads to indole derivatives with up to 94% yield and 82% ee27. 

Although less commonly investigated, several catalytic, enantioselective aziridination reactions have also been developed. As an example, copper complexed to a chiral bisoxazoline ligand such as shown in Scheme 8.12a has been shown to catalyze the addition of A-(p-toluenesulfonylimino)phenyliodinane across a double bond [58]. Some promising results have been obtained (Scheme 8.12b), but work to fully define and optimize the range of olefins susceptible to this process is still ongoing. 

Previously, every example of enantioselective conjugate radical additions featured asymmetric induction through the application of bidentate bisoxazoline chiral Lewis acids. A recent report, however, illustrates the utility of a new type of chiral bisoxazoline ligand known as DBFOX-Ph (59), which features a furan-containing bridge that offers tridentate chelation of the Lewis acid for asymmetric conjugate radical additions [25]. 

Hetero-Diels-Alder reactions have been used in the construction of amino-sugars, asymmetry being induced by the use of either a chiral Lewis acid catalyst or a chiral auxiliary. Thus, the 3-amino-hexuronic acid derivatives 61 were obtained with high de and ee using a copper(II) triflate catalyst with a chiral bisoxazoline ligand. 4-Amino-4-deoxy-D-erythrose and 4-amino-4,5-dideoxy-L-lyxose (63), the latter a potent inhibitor of a-L-fucosidase, were obtained from the D-pyroglutamic add-containing diene 62 (Scheme 19). ... 

Kobayashi et al. developed catalytic asymmetric 1,4-additions using chiral calcium species prepared from calcium isopropoxide and chiral bisoxazoline ligands 39, 166 and 168. They found that calcium pyBOX catalysts could effectively mediate catalytic asymmetric additions of 1,3-dicarbonyl compounds 4 to nitroalkenes 86, N-Boc-imines 138 or unsaturated amides 49 giving products 165,167 and 170, respectively. Neutral coordinative ligands worked well in these reactions, giving a noticeably faster rate of reaction... 

An advantage of using polyisobutylene is solubility in a variety of nonpolar solvents at ambient temperatures. Also, the terminal double bond of polyisobutylene can be readily transformed into various useful groups for attachment of catalysts or reagents. Thus, polyisobutylene was used as a catalyst support for anchoring a sulfur-cation-sulfur Pd(ll), as shown above. These catalysts were used to perform allylic substitution, Heck, and Sonogashira reactions [26]. Polyisobutylene was also used to support chiral bisoxazoline ligands for copper-catalyzed cyclopropanation reactions [27]. Other uses... 

An asymmetric version for the synthesis of diesters was published by the same group in 2001 [35]. By using a chiral bisoxazoline ligand in the presence of copper(l) triflate at 25 °C, terminal olefins were carbonylated to enantiomerically enriched diesters in good yields with up to 66 % ee (Scheme 8.6). 

When the coupling partner alkynes in the Larock indole synthesis were replaced with substituted allenes 37, the corresponding 3-methyleneindolines 38 were obtained in 94—95% yields and 80 82% enantiomeric pure in the presence a chiral bisoxazoline ligand 39. ... 

Allylpalladium complexes with BOX-type ligands and glucopyrano-oxazoline-palladium catalysts were used as catalysts for enantioselective allylic substitution (277). A chiral bisoxazoline ligand (BOXBZ) developed by Pfaltz has been used for asymmetric carbo- and heteroannulation reactions (278). An axial binaphthyl-based ligand possessing oxazolyl substituents (BOXAX) was developed by Hayashi and co-workers and successfully applied for the asymmetric Wacker-type cyclization (279). 

C-cycloadduct in which the carbon terminus of the dipole added to the p-carbon of the acceptor. When the process was catalysed by a combination of nickel perchlorate with chiral bisoxazoline ligand 9, the product was obtained in almost quantitative yield and with moderate enantioselectivity of 77% ee, as shown in Scheme 1.9. The authors showed that the enantioselectivity of... 

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