Bipyrrolidine

In 2008, Que and coworkers reported an asymmetric version of the dihydroxylation with a new type of ligands bearing bipyrrolidine as the chiral backbone [71]. The corresponding iron(II) complex showed general activity in the dihydroxylation of various olefins using H202- Satisfactory results are obtained with aliphatic as well as with aromatic olefins. For example, dihydroxylation of styrene gave styrene oxide and 1-phenylethane-1,2-diol in <1% and 65% yield, respectively (Scheme 10). 

Whereas E.J. Corey uses the derivative (5,5)-1432of 1,2-diphenyl-1,2-diaminoethane (13), M. Hirama and K. Tomioka use chiral Ai,A -dialkyl-2.2 -bipyrrolidines 15 and bis(3,4-diphenilpyrrolidines) I, respectively. The method of E.J. Corey is by far the superior one, the chemical yields and the ee excesses usually being in the range of, respectively, 80-95% and 92-98%. 

The first asymmetric direct Michael addition of enolizable aldehydes RCH2CH=0 to vinyl sulfones CH2=C(S02Ph)2 catalysed by /V-Pr -2,2 -bipyrrolidine (146) has been reported. The 1,4-adducts were obtained in good yields and enantioselectivities... 

Enantioselective dihydroxy lotion.2 Highly enantioselective osmylation of rraiif-disubstituted and monosubstituted alkenes obtains with Os04 oxidations in the presence of 1 equiv. of this chiral 2,2 -bipyrrolidine ligand at —78°. Note, however, that the enantioselectivity for osmylation of cis-disubstituted alkenes is only —65%... 

A diamine containing two directly connected pyrrolidine rings has been used as an additive in osmium tetroxide catalyzed dihydroxylations (Section D.4.4.). The synthesis from 2,2 -bipyrrole involves catalytic reduction, benzoylation, separation of the me so and dl forms by chromatography, amide hydrolysis, and resolution with tartaric acid26. The (S,S)-2,2 -bipyrrolidine thus obtained is then converted to the sterically hindered (. vV)-A,A -bis(3,3-dimcthylbutyl)-2,2 -bipyrrolidine [(S,S)-33] by acylation and reduction with lithium aluminum hydride27. 

The C2-symmetric 3,3 -benzyloxy-2,2 -bipyrrolidine 15 was used by Zhang and coworkers for the asymmetric Diels-Alder reaction of cyclopentadiene and ot,p-unsaturated aldehydes in the presence of perchloric acid as the cocatalyst. The reaction proceeds via a di-iminium intermediate and the desired cycloadducts were obtained in excellent yields and with very good stereoselectivities (Scheme 11.14). ... 

Scheme 11.14 Asymmetric Diels-Alder reaction of cyclopentadiene and a,p-unsat-urated aldehydes catalysed by the bipyrrolidine 15.

Lately, sulfones have become especially important substrates in organocatalysis [87]. First studies on the asymmetric conjugate addition of aldehydes to vinyl sulfones were carried out by Alexakis and Mossd employing as catalyst bipyrrolidine 30 (25 mol%) for the addition of linear and a-branched aldehydes to l,l-bis(benzenesulfonyl)ethylene [88], Large excess of aldehyde (10 equivalents) was required and moderate levels of enantioselection were obtained for linear aldehydes (53-80% ee), while reactions with a-branched nucleophiles led to racemic or very low selectivities (0-12% ee). With respect to the mechanism, the acyclic synclinal model proposed by Seebach and GoUnski [70] involving a trans enamine intermediate was postulated. 

L-proline as catalyst [ 109]. Further studies on the reaction were carried out by Alexakis et al. using the hydrochloride salt of lV-isopropyl-2,2 -bipyrrolidine (30, Hg. 2.4) as catalyst in CHCI3 as solvent. In this study the highest enantioselectivity (81%) was obtained for the addition of cyclohexanone to nitrostyrene also with a very high diaste-reoselectivity (syn/anli 94/6) [50]. As in the case of the conjugate addition of aldehydes, the observed syn selectivity was in accordance with the Seebach-GoUnski model [70]. 

A new class of C -symmetric 3,3 -dialkoxy-2,2 -bipyrrolidines (e.g., 50) have been designed and developed by Zhang and his co-workers. The catalysts were used in asymmetric organocatalytic Diels-Alder reactions of a,P-unsaturated aldehydes 28 and dienes. Scheme 3.17 [30]. 

After the success of Macmillan s catalysts, other types of chiral amine were disclosed and applied in the FCA reaction as activators of a,(3-unsaturated aldehydes. Reports from a few groups have revealed that diaryIprolinol silyl ethers [11], camphor sulfonyl hydrazine [12], chiral aziridin-2-yl methanols [13], and A-isopropylated bipyrrolidine [14] were efficient catalysts in the enantioselective alkylations of 4,7-dihydroindoles, 1-naphthols, and indoles. NEt3, benzoic acid, or... 

Very recently White and coworkers [62] designed a new catalyst [Fe(CF3-pdp) (CH3CN)2](SbFg)2 (CF3-pdp = V,V -bis(5-(2,6-di-(trifluoro)-methyl-phenyl)-2-pyridylmethyl)-2,2 -bipyrrolidine) that used a trajectory restriction strategy to achieve predictable, catalyst-controlled site-selectivity (Scheme 32). 

Andrey O, Alexakis A, Tomassini A, Bemardinelli G (2004) The Use of iV-AIkyl-2,2 -Bipyrrolidine Derivatives as Organocatalysts for the Asymmetric Michael Addition of Ketones and Aldehydes to Nitroolefins. Adv Synth Catal 346 1147... 

Independently, Alexakis and coworkers reported that 2,2 -bipyrrolidine catalyst 28 showed excellent catalytic activity in several types of asymmetric Michael addition reactions [143], It has been postulated that the isopropyl group on one of the Cj-symmetric pyrrolidine rings should block not only the back face against the approach of Michael acceptors but also shift the equiUbrium towards one of the two rotamers. Since then, closely related catalysts have also been reported [144]. Furthermore, different types of catalysts such as 29 have been shown to be useful in asymmetric Michael addition reactions [145-148],... 

Mosse and Alexakis [66] reported in 2005 the first organocatalyzed 1,4-conjugate addition of aldehydes to vinyl sulfones. The organocatalyst, N-tPr-2,2 -bipyrrolidine (2), induced a good enantioselectivity when using l,l-bis(benzenesulfonyl) ethylene (72) while phenyl vinyl sulfone (73) was not reactive under the same conditions (Scheme 34.26). As product 74 is sensitive to silica gel, it is accompanied by byproduct 75. To explain the observed selectivity, the authors suggested a transition state where the pyrroUdine moiety bearing the isopropyl substituent shields the Re face of the enamine and locks the conformation of the enamine intermediate. 

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