Mixed zinc reagent

Use of ferrocene 9 in combination with the mixed zinc reagent (ZnPh2/ZnEt2 = 1 2) allowed a wide range of diarylmethanols 27 to be prepared in a highly enantioselective manner [38]. A selection of products is shown in Scheme 2.I.2.8. 

A class of mixed zinc reagents, e.g., (trimethylsilylmethyl)(2-pyrrolyl or 2-indolyl)zincs, bearing one transferable functional group (2-pyrrolyl or 2-indolyl) and one nontransferable group (the trimethylsilylmethyl group), add efficiently to Michael acceptors, for example, as in Scheme 141 <1998T1471>. 

Figure 8.2) [4]. The initially obtained enantiomeric excess (ee) in this process was only 57%, and this was attributed to the competing background reaction. Later, Pu described protocols in which certain additives, such as methanol, were used to tame the reactivity of Ph2Zn [5]. The addition of diethylzinc to the reaction mixture led to the formation of a mixed zinc reagent, PhZnEt, which was found to be less reactive and thus more selective than Ph2Zn itself [6]. Additionally, Ph2Zn could be used in substoichiometric amounts (0.65equiv.), since both its phenyl groups were now available for the reaction.

Ishihara and coworkers also reported mixed zinc reagents, namely PhjZn/EtjZn, as the phenyl source for enantioselective phenyl additions to ketones (Scheme 7.51). The cat2ilyst was a chiral phosphoramides-Zn(II) complex prepared in situ [81]. These chiral Zn(II) cat2ilysts serve as conjugate Lewis acid-Lewis base catalysts (Figure 7.10). From a variety of aromatic and aliphatic ketones, optically active tertiary alcohols were obtained in high yields with high enantioselectivities (up to 98% ee) under mild reaction conditions (Scheme 7.51). 

Addition to Carbonyl Compounds. (TMSM)2Zn can be used for the preparation of a wide range of mixed organozinc compounds, in which the (trimethylsilyl)methyl (TMSM) moiety acts as a non-transferable group.As a result only a slight excess of the mixed zinc reagent is required in the reaction with aldehydes, a process which affords secondary alcohols in good yields (eq... 

Mixed copper-zinc reagents also react with alkynes to give alkenylcopper species that can undergo subsequent electrophilic substitution. 

Further optimization of this reaction was carried out with TFE as an achiral adduct, since reaction with TFE is much faster than that with neopentyl alcohol. We found that dimethyl- and diethylzinc were equally effective, and the chiral zinc reagent could be prepared by mixing the chiral modifier, the achiral alcohol and dialkylzinc reagent in any order without affecting the conversion and selectivity of the reaction. However, the ratio of chiral to achiral modifier does affect the efficiency of the reaction. Less than 1 equiv of the chiral modifier lowered the ee %. For example with 0.8 equiv of 46 the enantiomeric excess of 53 was only 58.8% but with 1 equiv of 46 it was increased to 95.6%. Reaction temperature has a little effect on the enantiomeric excess. Reactions with zinc alkoxide derived for 46 and TFE gave 53 with 99.2% ee at 0°C and 94.0% ee at 40°C. 

Scheme 8.3. Conjugate Addition and Alkylation Reactions of Mixed Copper-Zinc Reagents...

The second major advantage of this method is that a wide range of new cyclopropanating reagents with new properties became available. If a sufficiently acidic compound reacts with diethylzinc, a mixed zinc species is formed (equation 5). The second ethyl group can then be exchanged with an iodomethyl unit to generate a potentially reactive iodomethylzinc species. 

Thus, the hydroboration of 1-phenylcyclopentene with (—)-IpcBH, (99% produces, after crystallization, the chiral organoborane 126 with 94% ee. The reaction of 126 with Et2BH replaces the isopinocamphenyl group with an ethyl substituent (50 C, 16 h) and provides, after the addition of i-Pr2Zn (25 °C, 5 h), the mixed diorganozinc 127. Its stereoselective allylation leads to the fraw5-disubstituted cyclopentane 128 in 44% yield (94% ee trans cis = 98 2) see Scheme 43 ° . This sequence can be extended to open-chain alkenes and Z-styrene derivative 129 is converted to the anf/ -zinc reagent 130, which provides after allylation the alkene 131 in 40% yield and 74% ee (dr = 8 92). 

Allylic zinc reagents are highly reactive reagents which are prone to undergo carbozincation of weakly activated alkenes . Thus, the addition of the mixed methallyl(butyl)zinc 393 with the vinylic boronate 394 provides the intermediate zinc reagent 395. After the addition of an extra equivalent of ZnBri, CuCN 2LiCl and allyl bromide, the reaction mixture was worked up oxidatively providing the alcohol 396 in 83% yield. ... 

Chemla, Normant and coworkers also reported a one-pot 1,4-addition/carbocyclization domino sequence as a new access to 3-carbomethoxypyrrolidines. Conjugate addition of the mixed organocopper-zinc reagent n-BuCu(CN)ZnBr LiBr to the Michael acceptor 427 in ether at room temperature directly led after hydrolysis to the 3-carbomethoxypyr-rolidine 428 as a 84/16 diastereomeric mixture, the trans disubstituted isomer being predominant (equation 185). A similar explanation as described above was proposed for the stereochemical outcome264. 

Investigations by Mulvey and his group have uncovered very unusual structures associated with the mixed alkali metal-zinc reagents.For example, it has been found that a 1 1 mixture of KN(SiMe3)2 and ZnfNfSiMe, ), readily deprotonates toluene [Equation (7.1)] to afford... 

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