Diisopropylzinc, addition

Asymmetric amplification, in diisopropylzinc additions, 2, 386 Asymmetric arylation, phenols with lead triacetates, 9, 399 Asymmetric carboalumination, Zr-catalyzed, alkenes, 10, 272 Asymmetric carbonyl-ene reaction, characteristics, 10, 559 Asymmetric catalysis... 

Asymmetric amplification in autocatalytic additions of diisopropylzinc to some aldehydes 386... 

The first asymmetric autocatalysis with amplification of was observed in the automultiplication of a 5-pyrimidyl alkanol 80 (Figure l)169. When (5)-5-pyrimidyl alkanol 80 with as low as 2% is used as the asymmetric autocatalyst for enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde 88, the of the produced pyrimidyl alkanol (and the initial asymmetric autocatalyst) 80 increases to 10% (Figure 1, 1st run). Consecutive asymmetric autocatalyses using 5-pyrimidyl alkanol 80 with 10% have increased its to 57%, 81% and 88% , successively. During the reactions, the major (S)-enantiomer in the initial asymmetric autocatalyst has automultiplied by a factor of 238, while the slightly minor (R)-enantiomer has automultiplied by a factor of only 16. 

When enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde 89 was examined, simple 2-butanol with low (ca 0.1%) induces a tiny chirality in the initially produced alkanol 81 and the value of the finally obtained alkanol becomes higher (73-76%) due to the asymmetric autocatalysis (Table 2). Note that the value can be further amplified by subsequent asymmetric autocatalysis, as described in the preceding section. Various chiral compounds have been proved to act as chiral initiators. 

Scheme 22 Enantioselective addition of diisopropylzinc to aldehyde 11 using chiral a-deuterated alcohols as chiral inducers...

Abstract The addition of diisopropylzinc to prochiral pyrimidine carbaldehydes (Soai reaction) is the only known example of spontaneous asymmetric synthesis in organic chemistry. It serves as a model system for the spontaneous occurrence of chiral asymmetry from achiral initial conditions. This review describes the possible kinetic origin of specific experimental features of this reaction. It is shown that generic kinetic models, including enantioselective autocatalysis and mutual inhibition between the enantiomers,... 

The first experimental invention of spontaneous asymmetric synthesis was achieved only a little more than a decade ago in an organic reaction system by Soai and coworkers [9-15]. The Soai reaction (Scheme 1) comprises the addition of diisopropylzinc to prochiral pyrimidine carbaldehydes yielding isopropylzinc alkoxides that, after hydrolysis, are usually converted into stable chiral pyrimidyl alkanols. 

Since there were variations in the experimental conditions (such as the nature of the aldehyde or the number of performed reaction cycles) it remains possible that the event or the extent of symmetry breaking depend on these. Even if the first reaction cycle gives rise to only a small ee, further ones will certainly amplify this small bias and push it with its proper enantiomeric direction to the edges. Further influence could come from achiral additives. Kawasaki et al. assume in the case of the addition of achiral silica gel that this additive may provide an improved reaction platform by coordination of the aldehyde and involvement of a zinc atom from the reaction of diisopropylzinc with the acidic hydroxyl group of silica gel [40]. Further systematic experimental studies, which can also shed more light on the basic reaction mechanism, are required to better understand the differences in the results. 

Further insight into the structural aspects of the basic reaction process was given by NMR studies, which indicate that additional equilibria between the alkoxide dimers and diisopropylzinc molecules should be taken into account yielding RR-Z, SS-Z, and RS-Z association complexes [33,83]. Further studies in such a direction combined with kinetic experiments will be needed to decide about the closer reaction network in the Soai reaction (especially about the autocatalytic steps) in order to shine light on the possible catalytic action of monomer or oligomer species. 

With regard to diorganozincs other than primary dialkylzincs, various diorganozincs such as divinylzinc (> 96% ee, addition to benzaldehyde),4 difurylzinc (72% ee, addition to benzaldehyde),5 diphenylzinc (78-82% ee, addition to various aldehydes),6 and diisopropylzinc (93% ee, addition to benzaldehyde)7 have been utilized in the chiral (3-aminoalcohol catalysed reactions. Alkenyl(alkyl)zincs4b,c and alkynyl(alkyl)zincs8 afford the corresponding chiral allylic and propargyl alcohols. 

Highly enantioselective asymmetric autocatalytic reactions have been reported using chiral pyrimidyl-lla,b and quinolylalkanols (Scheme 12.2).Uc (5)-2-methyl-l-(2-methyl-5-pyrimidyl)-l-propanol (14b, 99.9% ee) autocatalyses the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde to afford 14b itself of the same configuration with 98.2% ee.ll Moreover 14a shows asymmetric autocatalytic reaction with amplification of ee. Thus, starting from (5)-14a with only 2% ee, four successive autocatalytic reactions afford (5)-14a with 88% ee.ub... 

In order to avoid this unfavourable effect of the functional groups in the dendrimer structure, a rigid hydrocarbon backbone without heteroatoms was synthesized. Dendrimers with poly(phenylethyne) backbones, bearing three and six ephedrine derivatives at the periphery, were studied in the alkylation of aldehydes and N-diphenylphosphinylimines and proved to be highly en-antioselective catalysts. For example, the system containing six catalytic sites catalyzed the addition of diisopropylzinc to aldehydes with enantioselectivi-ties of up to 86% ee. As a third backbone a polycarbosilane dendrimer was used, which is chemically inert and more flexible than the poly(phenylethyne)... 

Soai and co-workers have developed additions of diisopropylzinc to 2-alkynylpyrimidyl-5-carbaldehydes. The resulting alcohol allows a practically perfect asymmetric autocatalysis.216 Recently, they reported that an efficient amplification by a catalyst with as low as 10 5%ee gives practically enantiomerically pure (>99.5%ee) product in only three consecutive cycles.217 The product formed in situ with enhanced ee serves as an asymmetric autocatalyst. Thus, addition of diisopropylzinc to the carbaldehyde 64 in presence of 20 mol% of the alkanol (61-65 with 10 s% ee gives after 1.5 h (6)-65 with 57% ee. A new addition of the mixture diisopropylzinc/carbaldehyde 64 to the reaction... 

The dialkylzinc additions catalyzed by N,N-di-n-alkylnorephedrines (most typically DBNE) are not limited to primary organometallic reagents. Diisopropylzinc (with a secondary alkyl substituent) adds to benzaldehyde in the presence of a catalytic amount of DBNE to afford the corresponding alcohol with high ee (entry 4). The reaction of diisopropylzinc in the presence of other types of catalysts may result in the reduction of aldehydes. 

Soai has reported the remarkable example of asymmetric autocatalysis in carbonyl-addition reactions of diisopropylzinc [40- 3, 45]. Usually, zinc alkoxide forms an inactive tetramer. However, the use of pyridyl aldehyde as a substrate to give pyridyl alcohol product can loop the catalytic cycle without formation of the inac-... 

Soai et al. discovered and developed asymmetric autocatalysis (Figure 9), in which the structures of the chiral catalyst (5)-54 and the chiral product (5)-54 are the same after the addition of diisopropylzinc to aldehyde 53. Consecutive asymmetric autocatalysis starting with (S)-54 of 0.6% ee amplifies its ee, and yields itself as the product with >99.5% ee. Even chiral inorganic crystals, such as quartz or sodium chlorate, act as chiral inducers in this reaction. Soai et alls asymmetric autocatalysis gives us an insight to speculate on the early asymmetric reactions on this planet Earth. However, it can be argued whether such strictly anhydrous organometallic reactions are possible under the nonartificial conditions or not. 

The chiral catalysts 1 to 4 are highly enantioselective in the addition of di(prira-alkyl)zincs to aromatic aldehydes. (IS, 2i )-iV,iV-dibutylnorephedrine [1 (DBNE)] [5] possesses the advantage of its utility as a highly enantioselective catalyst even for the alkylation of aliphatic aldehydes to afford aliphatic sec-alcohols with up to 93% ee [5]. DBNE is also an appropriate chiral catalyst for the addition of diisopropylzinc [di(sec-alkyl)zinc] (98% ee) [15]. (S)-Diphenyl(l-meth-ylpyrrolidin-2-yl)methanol [2 (DPMPM) [6] catalyzes the enantioselective ethylation of aromatic aldehydes to afford almost enantiomerically pure sec-alcohols... 

Hydroboration (syn addition of H and B) followed by transmetallation with diethyl-or (with secondary boranes) diisopropylzinc provides a useful entry to diorganozinc species. Formation of the copper-zinc species allows reaction with activated electrophiles such as allyl bromide. See A. Bourdier, C. Darcel, F. Flachsmann, L. Micouin, M. Oestreich and P. Knochel, Chem. Ear J., 6 (2000), 2748. 

Soai K., Sato I., Shibata T., Komiya S., Hayashi M., Matsueda Y., Imamura H., Hayase T., Morioka H., Tabira H., Yamamoto J. and Kowata Y. (2003) Asymmetric synthesis of pyrimidyl alkanol without adding chiral substances by the addition of diisopropylzinc to pyrimidine-5-carbaldehyde in conjunct-tion with asymmetric autocatalysis, Tetrahedr. Asymm. 14, 185-188. 

A rather unconventional use of tetrathiaheHcene (P)-72 has been reported (2006TA2050). These 7-TH systems, without any functional groups, can act as chiral inducers in a chiral amphfication process related to the addition of diisopropylzinc to the pyrimidine-5-carbaldehyde 119 (Scheme 35). 

We found asymmetric autocatalysis of pyrimidyl alkanol 1 [1-10], Pyrimidyl alkanol 1 acts as asymmetric autocatalyst in the enantioselective addition of diisopropylzinc (/-Pr2Zn) to pyrimidine-5-carbaldehyde 2 to produce more of itself with the same absolute configuration [11] of >99.5% enantiomeric excess (ee) in a yield of >99% (Scheme 1) [12]. Thus, pyrimidyl alkanol 1 automultiplies in... 

The effectiveness of nucleophilic substitution of the dichlorophos-phido 12 led the authors to enlarge the scope of the reaction by preparing a set of phosphido complexes (Scheme 5). ° For example, the reaction of 14 with diisopropylzinc led to the formation of 15 as the major product. In addition, compound 14 was also able to react with alcohols, like menthol or p- Bu-phenol, yielding the desired alkoxy-17 and phenoxy-16, phosphido complexes with 63 and 88% yields, respectively. 

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