Isomerization hydrozirconation

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 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) ... 

The steric demand of the zirconocene moiety leads to rearrangements in the case of hydrozirconation of internal double bonds. Regardless of position or configuration of the double bond in the substrate, zirconium migrates to the terminal position of the alkyl chain via insertion and /TH-elimination steps. Such isomerization does not occur upon hydrozirconization of internal alkynes. 

Cross-coupling ofalkynes. A route to isomerically pure 1,3-dienes involves hydrozirconation of an alkyne followed by conversion to the alkyne complex 3, which couples with a second alkyne to give a metallacyclopentadiene 4. Treatment of 4 with dilute acid provides the diene 5, usually as a single isomer (>97%). Overall yields are in the range 53-80%. 

The addition of Cp2Zr(H)Cl, known as the Schwartz reagent [30], to different alkenes and alkynes is known to be a facile process [31]. Therefore, the hydrozirconation of a variety of readily available enynes 12 is among the first methods developed for the stereoselective preparation of dienyl zirconium reagents 13. This process is both completely chemo- and regioselective with a syn addition of the zirconium hydride across the alkyne [32] (Scheme 5). From the same intermediate, the Zr atom can be isomerized in its internal position such as in 15 via a zirconacyclopropene intermediate 14. Moreover, the addition of trimethylstannyl chloride to 14 led to the stannylated dienyl zirconocene 16 [33] (Scheme 5). 

The unique stereochemistry of the diene results therefore from the elimination step and not from a further isomerization of the dienyl zirconocene with zirconocene derivatives (i.e., Cp2Zr-catalyzed stilbene stereoisomerization) [78]), since the hydrozirconation reaction of several l -ene-3-yne and lZ-ene-3-yne derivatives with Cp2ZrH(Cl) leads only to the (E,E) and (Z, ) isomers, respectively, in good yields (see Scheme 5) [33]. 

Tertiary alkylzirconium compounds appear to be generally inaccessible even as intermediates. Tetra-substituted alkenes are not hydrozirconated at all also, zirconium is unable to migrate past a tertiary position in a carbon chain. Attempted hydrozirconation of an internal alkene which is blocked at both ends (20 equation 26) gives only isomerized alkene (21). The only exception, which appears to involve a tertiary intermediate, is found in the hydrozirconation of dienol (22) in equation (27). ... 

Definitive evidence for the role of heteroatom coordination may be seen in the hydrozirconation of al-kenoxide (29 equation 33) where the five-membered ring favors (30) (confirmed by the X-ray crystal structure). A related structure was obtained in equation (34) the 0-coordinated product (31) does not isomerize to the terminal alkylzirconium product (16) below 140 "C. (At 140 C it slowly decomposes to 17, presumably via 16 cf. equation 22 above.) In contrast, hydrozirconation of dienols shows preferred reactivity of the double bond remote from the —OH group an example is shown in Table 3. Probably the first equivalent of (6) reacts with the —OH group both to increase steric bulk and prevent... 

Hydrozirconation of vitamin D3 (39) gives a mixture of four diastereomers resulting not only from addition to either face of the reacting exocyclic double bond, but also isomerization of the nonreacting 5,6-double bond (equation 41), even though no isomerization of unreacted (39) was detected. No explanation was offered. Partial isomerization of a double bond during hydrozirconation of a triple bond has also been observed. ... 

Protonolysis can also be effected with weaker acids in some cases this may be essential. For example, hydrozirconation of alkynic alcohols Me(CH2)nC=C(CH2)mOH with 2 equiv. of (6), followed by hydrolysis with 2% aqueous NH4CI, affords the corresponding cis-alkenol in high yield and selectivity, whereas use of aqueous HCl causes both cis-trans isomerization and allylic rearrangement. Protonolysis by weak acid may be slow enough for other reactions to compete TBHP can be used as an oxidant (see below). 

Hydrozirconation is not sufficiently reversible to liberate the organic group as an alkene by displacement but that can be achieved via hydride abstraction with trityl ion. This generates a sequence for net alkene isomerization in the counterthermodynamic direction (equation 42). ... 

Annby, U., Karlsson, S., Gronowitz, S., Hallberg, A., Alvhaell, J., Svenson, R. Hydrozirconation-isomerization. Reactions of terminally functionalized olefins with zirconocene hydrides and general aspects. Acta Chem. Scand. 1993, 47, 425-433. 

As mentioned earlier, hydrozirconation of internal alkenes gives terminal alkylzir-conium compounds. The isomerization occurs so quickly that no intermediates are observed. The mechanism of the reaction is a series of insertions and /3-hydride eliminations. 

Hydrozirconation occurs with yyn-addition of the Zr-H bond across a C=C or C=C bond (equation 8.16). Due to lower steric hindrance, the addition also tends to be regiospecific, with the zirconium attached to the less substituted position (just as in hydroboration). Internal alkenes and alkynes isomerize to 1-alkyl and 1-alkenyl complexes, respectively—presumably by alternating reactions of insertion and deinsertion—until the complex with the least steric hindrance is formed. 

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