Nitriles hydrozirconation

The chemoselectivity of Schwartz s reagent (1) toward alkynes, alkenes, nitriles, and carbonyl groups, and thus its general functional group compatibility, can be modulated. However, it is important to keep in mind that the presence of functional groups may have regiochemical consequences on the hydrozirconation reaction. 

Nitriles [153, 211] are tolerated by an equivalent of reagent in the presence of a particularly reactive site of unsaturation, such as a terminal alkyne or vinyl function, whereas methacrylonitrile gives only C N hydrozirconation (Scheme 8-26) [215]. 

Scheme 8-26 Hydrozirconation of alkenes with nitrile function...

Alkynes are universally hydrozirconated as well the only failure in the literature is that of a perfluori-nated compound, C7Fi5(2sCH. Alkynes appear to be more reactive than alkenes, both by qualitative comparison and from the results on enynes (Table 6 also see Section 3.9.3.3.1), Furthermore, hydrozirconation of alkynes can compete with reduction of unsaturated functional groups such as nitriles and esters (Table 5), which is generally not true for alkenes. Dienes can be cleanly monohydrozirconated if one of the double bonds is terminal other cases are considered in Section 3.9.3.3.I. 

Of course, these findings do not automatically mean that such functional groups cannot be tolerated that depends upon relative rates. For instance, hydrozirconation of nitriles can be relatively slow complete reaction of RCN under standard conditions required 72 h, 14 h and 1.5 h, respectively for R = Me, Ph, Bn, Consistent with previous indications that alkynes are more reactive than alkenes towards (6), hydrozirconation of an alkyne can be carried out in the presence of a nitrile group (see Table 5), whereas methacrylonitrile gives only C N hydrozirconation (equation 20). ... 

Hydrozirconation. Hydrozirconation of nitriles by Cp2Zr(H)Cl followed by reaction with RCOCl and quenched with nucleophiles gives rise to functionalized amides such as acylaminals and acyl hemiaminals (by adding alcohols and water, respectively). ... 

Hydrozirconation of alkenes as a route to rr-alkylzirconiums is limited by other reactive functional groups e.g., alkynes react more readily than alkenes with (/j -Cp)2ZrHCl, and other reactive functional groups with ( / -Cp)2ZrHCl include alcohols, aldehydes, ketones, carboxylic acids, carboxylic acid esters, nitriles and thiocarbonyls . Alcohols may be protected either as alkyl ethers or as trialkylsilyl ethers. 

The diastereoselective additions of chlorotitanium enolates of 7V-propionyl thiazolidinethione 133 to various metalloaldimines 134, available from hydrometallation of the corresponding nitriles, furnish a mixture of azetine 135 and tetrahydropyrimidinone 136 <04H(62)217>. Among the three hydrometallation methods evaluated, the hydrozirconation process proves to be the best in terms of the yield and selectivity. 

The other significant variation of the prototypical Kulinkovich reaction is the so-called Kulinkovich-de Meijere reaction, where de Meijere extended the substrates from esters to amides. Other carboxylic acid derivatives including (cyclic) carbonate, imides, and nitriles also react with the key Kulinkovich intermediate. Szymoniak developed an efficient new synthesis of cyclopropanes via hydrozirconation of allylic ethers (e.g., using Cp2Zr(H)Cl) followed by addition of a Lewis acid (e.g., BFa OEta). Casey et al. further investigated the stereochemistry of this interesting cyclopropanation reaction using deuterated allylic ethers. ... 

Ethers and halogens do not interfer in hydrozirconation. However zirconium hydrides can reduce several types of carbonyl groups to alcohols. Nitriles are reduced to aldehydes. Consequently, these functions have to be protected. 

SCHEME 9 Acylaminal formation through nitrile hydrozirconation, acylation, and alcohol addition. 

Scheme 8). This report described the hydrozirconation of dimethylmalono-nitrile " to form bis-metalloimine 34. A number of electrophiles can react with 34, though from our perspective the most compelling reaction was the coupling with pivaloyl chloride to form bis-acylimine 35 in 94% yield. Thus, we envisioned a multicomponent reaction in which a nitrile, an acid chloride, a metal hydride, and an alcohol could combine in a single reaction flask to form an W-acyl aminal. 

In hydrozirconation of alkenes by Cp2ZrHCl, terminal alkenes insert in the anti-Markovnikov direction to give a stable 1° alkyl. Internal alkenes, such as 2-butene, insert to give an unstable 2° alkyl, that -eliminates to give 1- and 2-butene. The 1-butene can now give a stable 1° alkyl that is the final product. This is particularly noteworthy because the free terminal alkene is less stable than the internal alkene. Tlie outcome arises because the 1° alkyl is thermodynamically more stable than a 2° alkyl for steric reasons. The 1° alkyl, R, can subsequently be functionalized in a number of ways to give a variety of RX derivatives. Hydrozirconation is also effective with less reactive substrates, such as nitriles, where addition of Zr-H across the C=N bond is possible. ... 

True to its nature as an early transition metal, zirconium displays considerable Lewis acidity and binds to hard Lewis bases such as carbonyl groups, thus facilitating hydride transfer and reduction. In general, amides, ketones, aldehydes, and nitriles are not compatible with alkene and alkyne hydrozirconation conditions. Alkynes are selectively hydrozirconated in the presence of esters, but only stericaUy hindered triisopropylsilylesters survive the slower hydrozirconation of alkenes. Acylsilanes are also readUy tolerated in hydrozirconation, and carbamates, acetals, epoxides, sUylethers, alkyl- and phenylethers. 

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