Hydrozirconation, of alkenes

The regioselective hydrozirconahon of internal unsymmetrical alkenes remains a challenge, as it could considerably expand the use of zirconocene complexes. Little is known about the mechanism of zirconium migration along an alkyl chain. 

3 Hydrozirconation across Carbon-Carbon Multiple Bonds 1259 TBDPSO  

contrary to what was reported previously, the olefin dissociates from the zirconium metal complex. This conclusion was further supported by other experimental observations. However, it cannot be completely excluded that competition between dissociative and direct rearrangement pathways could occur with the different isomerization processes studied up to now. Note that with cationic zirconocene complexes [Cp2Zr-alkyl], DFT studies suggest that Zr-alkyl isomerizations occur by the classical reaction route, i.e. 3-H transfer, olefin rotation, and reinsertion into the Zr-H bond the olefin ligand appears to remain coordinated to the Zr metal center [89]. 

Formation of the least-hindered alkylzirconium complex during the course of the hydrozirconation-isomerization process of alkenes can be altered by the presence of aromatic rings, additional conjugative double bonds, chelating heteroatoms [81, 94] or groups that can be lost by elimination [95, 96]. 

The presence of functional groups containing oxygen-, nitrogen-, and phosphorus-chelating heteroatoms does frequently have regiochemical consequences in the 

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

Negishi previously reported that a wide variety of Lewis-acidic compounds catalyzed hydrozirconation of alkenes such as 1-decene 108 with /-BuZrCp2Cl.126 It was found that the reaction of 1-decene with 1.1 molar equiv. of TIB A, in the presence of 2-5 mol% of chlorine-containing late transition metals, led to the formation of 1-iododecane 110 after treatment of the product with iodine (Table 9). 

The only other alkenyl carbenoid with a proton trans to the halide that can readily be generated by deprotonation is the parent 1-lithio-l-chloroethene 57 [43] (Scheme 3.13). Insertion into organozirconocenes arising from hydrozirconation of alkenes and alkynes, followed by protonation, affords terminal alkenes and ( )-dienes 59, respectively [38]. The latter provides a useful complement to the synthesis of 54 in Scheme 3.12 since the stereocontrol is >99%. 

Acylzirconocene chloride derivatives are easily accessible in a one-pot procedure through the hydrozirconation of alkene or alkyne derivatives with zirconocene chloride hydride (Schwartz reagent) [Cp2Zr(H)Cl, Cp = cyclopentadienyl] and subsequent insertion of carbon monoxide (CO) into the alkyl— or alkenyl—zirconium bond under atmospheric pressure (Scheme 5.1) [2],... 

The hydrozirconation of alkenes will generally result in positional isomerization of the Zr to the least-hindered position. The Zr-intermediate can be replaced with Br (Br2, NBS), I (I2), Cl (NCS). OH (MCPBA, or basic aq. hydrogen peroxide). 

Hydrozirconation usually takes place readily at or slightly above room temperature, in benzene or toluene. The reactivity pattern of alkenes in hydrozirconation is the same as in hydroboration, except that tetrasubstituted alkenes are unreac-tive.457,460 A unique feature of hydrozirconation of alkenes is that, with some exceptions, terminally zirconated addition products are formed exclusively. Since isomeric alkenes cannot be isolated, zirconium moves rapidly along the chain without dissociation. Tertiary zirconium intermediates seem to be so unstable that the isopropylidene group never undergoes hydrozirconation [Eq. (6.75)],460 and hence, 1-methylcyclohexene fails to react.460 The reason is apparently steric, since the alkene must fit into the somewhat bent sandwich structure of the reagent (41) ... 

A reaction that is frequently applied in synthesis is the hydrozirconation of alkenes 181... 

Acylzirconocene chlorides are easily accessible in a one-pot procedure through the hydrozirconation see Hydrozirconation) of alkene or alkyne derivatives with the Schwartz s reagent and subsequent migratory insertion see Migratory Insertion) of carbon monoxide into the alkyl- or alkenyl zirconium bond. The stability of the acylzirconocene chlorides is remarkable at room temperature, and consequently allows many applications in organic synthesis. 

Examples of reported hydrozirconations of alkenes and alkynes are summarized in Tables 2-6. Simple alkenes appear always to react as long as they are no more than trisubstituted. The only reported failure is that of a long chain internal alkene, triacont-15-ene, but such alkenes have subsequently been successfully hydrozirconated, albeit at slightly elevated temperature. The order of reactivity, based primarily on qualitative observations, is terminal alkene > internal alkene (cis = trans) > exocyclic alkene > cyclic alkene = trisubstituted alkene. Trisubstituted cyclic olefins and tetrasubstituted olefins do not react. Representative examples are shown in Table 2. 

Table 3 Hydrozirconation of Alkenes with Oxygen-containing Functional Groups...

For acyclic alkenes, the facile rearrangement process obviates most possibilities of stereoselective transformation. The one exception is that of stereospecific isotopic labelling, for which hydrozirconation is a potentially powerful technique compounds of type Bu CHDCHDX (36), useful for NMR-based mechanistic studies, are conveniently obtained as in Scheme 9. This requires that four separate processes — hydrozirconation of alkyne, cleavage of alkeiiylzirconium, hydrozirconation of alkene and cleavage of alkylzirconium — all be completely stereospecific. 

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. 

Alkylmetallation The title compound effectively promotes the reaction of alkynes with alkylzirconium species derived from hydrozirconation of alkenes. 

Hydrozirconation of alkenes. This organic metallic reagent reacts with olefins at 25-40° to form alkylzirconium complexes of the type (C5115)2 Zn(R)Cl, in which the transition metal moiety is attached to the least hindered position of the olefin. For example, when a suspension of (1) in benzene is shaken with 1-octene or either cis- or tran -4-octene, (2) is formed in quantitative yield. Thus internally metalated zirconium compounds undergo rearrangement much more rapidly than organoboron or aluminum analogs. Other examples of hydrozircon-ation are formulated. Very hindered olefins e.g., tetramethylethylene) fail to react at 40°. 

Transmetalation. Carr and Schwartz have found that an organic group bound to zirconium can be transferred to aluminum. Thus reaction of 1, obtained by hydrozirconation of alkenes or alkynes, with AlCln results in a color change from bright yellow to orange as an organoaluminum dichloride is formed. On addition of an acid chloride, a ketone (2) is formed rapidly. This new ketone synthesis proceeds in high yield from alkyl- and alkenylaluminum dichlorides. 

Assuming for Eq. 6.4 T AS 9 kcal/mol, the small value for AGreac —4 kcal/mol permits facile reversibility of the alkene insertion, double bond migration (by successive yS-H elimination/readdition. Scheme 6.7), and the easy thermodynamic manipulation to drive the reaction in either sense, in the so called hydrozirconation of alkenes (Eq. 6.5) [29]. 

Conjugate addition of alkenes. Hydrozirconation of alkenes followed by addition of a catalytic amount of CuBr S(CH3)2 results in in situ preparation of alkyl cuprates that undergo 1,4-addition to an enone. 

An important application of alkene insertion is hydrozirconation of alkenes by Cp2ZrHCl. Terminal alkenes insert in the anti-Markownikov direction to give a stable 1° alkyl (Eq. 7.24). Internal alkenes, such as 2-butene, insert to give an unstable 2 alkyl, which is not observed. This intermediate P eliminates to give 1- and 2-butene. The 1-butene can now give the stable 1° alkyl, the observed product (Eq. 7.25). This is a particularly noteworthy reaction because the terminal alkene is less stable than the internal alkene. The insertion goes in the way it does because the 1° alkyl is more stable than any 2° alkyl, probably for steric reasons. The 1° alkyl can now be functionalized in a number of ways as discussed in Chapter 14. 

Despite the low intrinsic reactivity of alkylboranes, Pd-catalyzed alkylation with alkylboron compounds holds considerable promise as a unique and chemoselective alkylation method. It is uifique in part because hydroboration of alkenes is by far the most general and dependable method for stoichiometricaUy converting alkenes into organometals and in part because alkylboron compounds thus generated can satisfactorily participate in Pd-catalyzed alkylation under basic conditions, hi this connection, it should be noted that the current scopes of hydroalumination and hydrozirconation of alkenes are much more Umited than... 

One application of alkene insertion is hydrozirconation of alkenes by Cp2ZrHCl. Terminal alkenes insert in the anti-Markownikov direction to give... 

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