Diisopropylzinc

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

For internal olefins, the hydroboration step is slower, taking days rather than hours, and in this case the boron-zinc exchange requires the use of Zn(Pr )2 (Scheme 5). The reaction is stereospecific, provided that the diisopropylzinc is metal halide free.29,30... 

Highly efficient syntheses of both hetero- and homoleptic diorganozinc compounds, such as 6 and 7, were achieved by the UV (X > 280 nm) irradiation of mixtures of functionalized organoiodides and diethyl- or diisopropylzinc (Scheme 7).34 Irradiation with ultraviolet light avoids the use of a large excess of diethylzinc, which often furnishes homoleptic diorganozincs rather than the desired heteroleptic ones. Reaction times rarely exceed 2 h and conversions from 55 to 95% were commonly achieved. 

Dialkylzinc compounds have a tendency to form colored, and sometimes paramagnetic, adducts with 7r-acceptor ligands. The potentially bridging nitrogen donor pyrazine (and 4,4 -bipyridine) formed dinuclear complexes, Scheme 31, while the chelating 2,2 - bipyridine formed mononuclear adducts with diisopropylzinc.78 In the bis(diisopropylzinc)-pyrazine adduct 33, the presence of an unpaired electron was detected, but the resolution of the ESR spectra was insufficient for an unambiguous structural assignment. 

A recent interesting example of the chiral amplification of a small initial e.e. has been reported by Soai et al. [113,114] involving the induction of a chiral center in an achiral aldehyde using diisopropylzinc as an alkylating reductant and a very small... 

Recently, the intramolecular nitrile oxide-alkene cycloaddition sequence was used to prepare spiro- w(isoxazolines), which are considered useful as chiral ligands for asymmetric synthesis (321). Reaction of the dibutenyl-dioxime (164) (derived from the diester 163) with sodium hypochlorite afforded a mixture of diastereomeric isoxazolines 165-167 in 74% combined yield (Scheme 6.80) (321). It was discovered that a catalytic amount of the Cu(II) complex 165-Cu(acac)2, where acac = acetylacetonate, significantly accelerated the reaction of diisopropylzinc... 

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. 

R)- and (S)-pyrimidyl alcohols (78), prepared from reaction of the corresponding pyrimidylaldehyde with diisopropylzinc, are also autocatalysts starting from a near racemic seed , a large positive non-linear effect gives >99% ee.221... 

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... 

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

Fig. 13 Association of diisopropylzinc with the pyrimidine aldehyde. Such significant aryl ring CH chemical shift changes require low temperature analysis...

In the presence of excess diisopropylzinc, the EXSY spectrum in both thf and toluene shows rapid interconversion between zinc-bound isopropyl groups of the zinc reagent and alkoxide dimer (Fig. 15). The reaction occurs for both racemic and homochiral dimers with comparable facility. In toluene, the rate... 

Fig. 15 EXSY spectrum of a mixture of homochiral Zn alkoxide and excess diisopropylzinc in toluene-dg. The exchange peaks at 1-1.5 ppm are Zn-bound methyl groups the high field cross-peak belongs to the isopropyl methine protons...

Table 1 Solvent effects on the course of autocatalytic reaction between the methylpyrim-idinal and diisopropylzinc...

In the course of NMR studies of the autocatalytic system in CyDg, several experiments were carried out in which the 2-TMS-alkynylpyrimidine-5-aldehyde was directly mixed with diisopropylzinc at low temperatures and allowed to warm until the reaction was complete. The dimeric product can then be observed directly, and would be expected to be racemic since there are no internal or external chiral influences on the reaction. This was not the case, and an imbalance in favour of the homochiral form was sometimes observed a striking example is shown in Fig. 17. Since there is no workup... 

The enthalpies of trimers and tetramers were also calculated as part of this study. At the trimer level - important because this is the initial product of the reaction [dimer + zinc alkyl + aldehyde] - the most stable structures are macrocyclic. At the tetramer level there are two species of comparable enthalpy. One is the well-described cubic tetramer, and the other a barrel-like species that is conceptually related to two N - Zn lined dimers. The specific value derived from these calculations is only apparent when compared with the later computational work on the real diisopropylzinc-derived species. This highlights the importance of steric effects involving the more bulky isopropyl groups as a defining feature of asymmetric autocatalysis [80]. 

Fig. 20 Preferred ground-state conformations of the diisopropylzinc-derived homoehiral dimer (Ar, Ar syn) and the heterochiral dimer (Ar, Ar anti) from DFT calculations...

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. 

Scheme 6 Minimal kinetic model for the Soai reaction. A = pyrimidine carbaldehyde, Z = diisopropylzinc, R or S = enantiomeric zinc alkoxide, RR or SS = homochiral zinc alkoxide dimers, and RS = heterochiral zinc alkoxide dimer...

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. 

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