Diethylzinc, transmetalation

Three approaches to zinc enolates are commonly adopted the process associated to the classical Reformatsky reaction is based on the insertion of Zn(0) into the carbon—halogen bond of an a-haloester. Two additional routes involve (i) transmetallation of a lithium enolate with a Zn(II) salt (Section V.A) and (ii) the transition-metal-catalysed conjugate addition of diethylzinc to Michael acceptors (Section V.B). 

Non-aromatic organolithium compounds can be prepared by transmetallation of resin-bound stannanes [25] or by deprotonation of alkynes [26], triphenylmethane [27], or other resin-bound C II acidic compounds with lithium amides or similar bases (Figure 4.3). The reaction of polystyrene-bound trialkylboranes with diethylzinc yields resin-bound alkylzinc derivatives [28]. 

An example for the use of the boron-zinc exchange reaction for copper-mediated SN2 -substitutions of allylic electrophiles is the hydroboration of nitroolefin 130 with diethylborane, followed by successive transmetallation of the borane 131 with diethylzinc and CuCN-2LiCl, and final trapping with allyl bromide to give the product 133 with 83% yield over four steps (Scheme 34).34,34a This transformation again demonstrates the tolerance of the method towards functional groups and acidic hydrogen atoms. 

As mentioned in Section 9.12.2.1.1, the boron-zinc exchange can be performed stereoselectively if diisopropyl-zinc instead of diethylzinc is used. For example, hydroboration of the chiral, racemic endocyclic olefin 134 with diethylzinc, followed by twofold transmetallation and electrophilic capture of the resulting copper intermediate with allyl bromide was used for the highly diastereoselective formation of the stereotriad in product 136 (Scheme 35).35,35a 103 QorreSp0nding enantioselective transformations were carried out with chiral boranes and catalytic amounts of copper salts (see Section 9.12.2.2.2).36... 

A transmetallation to titanium derivatives - also promotes the addition of various zinc organo-metallics to carbonyl cmnpounds. However, the functional group tolerance seems to be limited (see Scheme lO), - - Interestingly, diethylzinc reacts with aromatic 1,2-diketones to give a-ethoxy ketones (see equation 10). ... 

The heptynoate sulfoxides 57 obtained in three steps from 3,3-dintethylbut-l-yne are cyclised to tetrahydrothiopyrans on treatment with diethylzinc under Pd-catalysis the overall process is an intramolecular sulfinylzincation. The vinylzinc intermediate, which is formed with high syw-selectivity, can be transmetalated and trapped with electrophiles to give trisubstituted vinylic sulfoxides. Oxathianes can be formed in an analogous manner though in somewhat lower yields <04H(62)263>. 

Pure diarylzincs, including nuclear-substituted ones, are best prepared either by this method, heating zinc and the diarylmercury in, e.g., boiling xylene,146 147 or from zinc chloride and phenyllithium.148 Diarylzincs can, however, also be obtained by transmetallation, e.g, by interaction of diethylzinc and the appropriate triarylboron.149... 

The enantioselective addition of functionalized dialkylzinc reagents to aldehydes is possible using a chiral Ugand and a Lewis-acid catalyst. The dialkylzinc reagents can be prepared by transmetallation (from the corresponding iodides or boranes) with diethylzinc. Selectivities are often best with aromatic aldehydes or... 

Allylethylzinc A reagent (2) of this type is prepared by hydroboration of 1-hexyne with dicyclohexylborane (1 equiv.) to form an (E)-l-alkenylborane 1, which undergoes transmetalation to form 2 on treatment with diethylzinc. This reagent adds to an aldehyde in the presence of the catalyst (—)-3-ejco-(dimethylamino)isoborneol (DAIB, 3) to form a secondary (E)-allylic alcohol in 70-95% yield with 79-98% ee. 

Although mechanistically different, functionalized alkenylsilanes are prepared stereoselectively by the reaction of 1-alkynes with iodotrimethylsilane (123) and diethylzinc. At hrst oxidative addition of 123 to Pd(0) generates 125. Then insertion of 1-octyne to 125 affords the alkenylpalladium 126. Transmetallation with Et2Zn gives 127 and reductive elimination provides the alkenylsilane 124. The reaction can be regarded as a Heck-type reaction of alkyne with MesSi-I, followed by Negishi coupling [37]. 

A rationale for this stereochemical outcome is outlined in Scheme 20, which involves oxidative addition of the lactone to Pd(0) with inversion of configuration, transmetallation with diethylzinc with retention of configuration, and allylation of benzaldehyde through a six-membered chair-like transition state, placing the phenyl group in an equatorial position. The generality of this reaction pattern is demonstrated with other cyclohexenyl and cyclopen-tenyl benzoate derivatives. 

In the same year, Roland and coworkers described a chiral silver-NHC complex with a tert-butyl substituted backbone for copper-catalyzed addition of Et2Zn to 2-cyclohexanone. However, the addition product was isolated in low enantioselectivity (23% ee) [77]. Later on, Alexakis et al. modified the carbene structure to improve the enantioselectivity (Scheme 3.51) [78]. By using the chiral silver-NHC salt 90 to transmetallate and generate the Cu catalyst, the asymmetric conjugate addition of diethylzinc to 2-cycloheptanone was achieved in good yield (95%) and enantioselectivity (93% ee). 

Scheme 7.50 Transmetallation of phenylboronic acid with diethylzinc and enantioselective addition to ketones, as described by Yus and coworkers [80].

The proposed mechanism involves the regioselective c/s-hydroboration of the 4-bromo-l,3-enyne as observed by Zweifel [2] followed by addition of hydride, originating from t-BuLi [3], to initiate a 1,2-metalate rearrangement forging the C-C bond with inversion at the vinylic center (Scheme 2). This key step enables the stereospecific character of the whole process. To circumvent the low reactivity of (Z)-vinylborane toward aldehydes, the corresponding (Z)-vinylzinc was prepared by transmetalation with diethylzinc and reacted successfully with carboxaldehyde. The isolation of aUylic alcohols in high yields was subordinated to a careful selection of the... 

The chiral 6is-(sulfonamide) 510 catalyzes the enantioselective addition of boronic acids to aromatic ketones in the presence of diethylzinc. Actually, this reaction proceeds via the transmetalation of a boronic acid giving the corresponding organozinc intermediate. The reaction produces interesting tertiary diaryIcarbinols such as 511 in up to 93% ee (Scheme 2-147, eq. Rudolph et al. have shown that this approach can... 

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