Isomerization hydroalumination

Early attempts by Asinger to enlarge the scope of hydroalumination by the use of transition metal catalysts included the conversion of mixtures of isomeric linear alkenes into linear alcohols by hydroalumination with BU3AI or BU2AIH at temperatures as high as 110°C and subsequent oxidation of the formed organoaluminum compounds [12]. Simple transition metal salts were used as catalysts, including tita-nium(IV) and zirconium(IV) chlorides and oxochlorides. The role of the transition metal in these reactions is likely limited to the isomerization of internal alkenes to terminal ones since no catalyst is required for the hydroalumination of a terminal alkene under these reaction conditions. 

Bis(diamino)alanes (R2N)2A1H were used for the hydroalumination of terminal and internal alkenes [18, 19]. TiCb and CpjTiCb are suitable catalysts for these reactions, whereas CpjZrCb exhibits low catalytic activity. The hydroaluminations are carried out in benzene or THF soluhon at elevated temperatures (60°C). Internal linear cis- and trans-alkenes are converted into n-alkylalanes via an isomerization process. Cycloalkenes give only moderate yields tri- and tetrasubstituted double bonds are inert. Hydroaluminahon of conjugated dienes like butadiene and 1,3-hexa-diene proceeds with only poor selechvity. The structure of the hydroaluminahon product of 1,5-hexadiene depends on the solvent used. While in benzene cyclization is observed, the reaction carried out in THF yields linear products (Scheme 2-10). 

Alkynes are much more reactive toward hydroalumination than alkenes. Hence, they readily react with both dialkylaluminum hydrides and LiAlH4 under mild conditions in the absence of a catalyst [1]. However, it is not always possible to avoid side reactions and subsequent transformation of the vinylalanes formed in this transformation [81, 82]. In addition, ds-trans-isomerization of the metallated C=C bond can take place, thereby reducing the stereoselectivity of the overall reaction [83]. 

In general, transition metal-catalyzed hydroaluminations of alkynes occur in a syn fashion, i.e., both aluminum and hydride are added to the same face of the 7i-bond. Isomerization of the initially formed vinylalane is usually not observed under the mild reaction conditions used for these transformations. 

In this synthesis (Scheme 6), the C2-symmetri-cal triacetonide of D-mannitol (32) is converted via the epoxide 33 and its nucleophilic addition product 34 to the propargylic alcohol derivative 35. From this intermediate, the Z-configured vinyl iodide 36 is stereoselectively obtained by hydroalumination/iodination. The Pd-catalyzed Heck cyclization then affords the isomerically pure product 37, which represents a potential building block for the synthesis of la,2y5,25-trihy-droxy-vitamin D, following the classical Wittig strategy of Lythgoe. 

With alkenes having internal C=C bonds, hydroalumination is disfavored by both kinetic and thermodynamic factors, and the uncatalyzed reaction is generally unfeasible. The hydroalumination of internal alkenes can be catalyzed by the addition of titanium(IV) alkoxides but the same catalysts also promote the isomerization of the secondary aluminum alkyls generated into their primary isomers (equation 16). ... 

In contrast with the impracticality of hydroaluminating open-chain internal alkenes, all the unsubstituted cycloalkenes can be usefully hydroaluminated, with titanium catalysis if need be, since isomerization of the C=C bond is of no significance. 

Finally, in uncatalyzed hydroaluminations with organosubstituted alkynes, the initially formed syn adduct can isomerize to the more stable anti adduct by way of the dialuminoalkane (equation 24). ... 

From all available evidence it is reasonable to conclude that the hydroalumination of both alkenes and alkynes by R2AIH occurs in a kinetically controlled syn manner and that any anti adduct formed results from a subsequent isomerization to the more stable configuration. In many situations the syn adduct can be isolated or detected prior to isomerization and its conversion to the anti adduct monitored. " In Table 5 are summarized the stereoselectivities observed in the hydroaluminations of a spectrum of substituted alkynes under various conditions. It is noteworthy that the thermal isomerization of the syn adduct can proceed with remarkable facility (at 0 °C) when a TMS or MesGe group is attached to the C=C linkage. 

Distinctly less is known about the anti hydroalumination adducts obtained from alkynes with MAIH4 or MAIR3H reagents (equation 9). These adducts could be the direct result of a trans addition but, pending further information, they might also arise from initial syn addition and subsequent isomerization. 

With MAIIL,H4-fl reagents, knowing the kinetic order of the reaction would prove most helpful in discerning whether the A1—H addition occurs initially in an anti manner, or whether a syn addition is followed by an isomerization to the anti adduct. A direct anti hydroalumination would likely require the synergistic action of 2 mol of MAIR3H in the rate-determining step and thus would be second-order in complex hydride (equation 37). 

This study opens up the possibility that hydroaluminations by LAH or LiAlBu 2MeH actually occur by the dissociation of such complex hydrides into AIH3 and R2AIH at higher temperatures. Steps of conventional syn hydroalumination, aluminum exchange and vinylic lithium isomerization could then lead to the anti adduct (Scheme 10). 

Since hydroalumination by neutral aluminum hydrides is an electrophilic attack on a C= or C=C linkage, the reaction can be accelerated by Lewis acids such as aluminum halides, and be retarded by Lewis bases like R3N, R2O or even unsaturated R3AI cf. equation 38). Such reagents also exert an effect on the syn or anti character of the A1—H adduct. Evidence suggests that Lewis acids or bases principally affect the rate of isomerization of the initial syn adduct into the generally more stable anti adduct Lewis bases retard such isomerizations, while Lewis acids promote them. The presence of ethers or tertiary amines stabilize the syn adducts of alkynyl-silanes and -germanes (47) and permit such adducts to be formed in >95% geometrical purity (Scheme 12). ... 

Hydroalumination. The treatment of alkynes with diisobutylaluminum hydride in hydrocarbon solvents results in a aT-addition of the Al-H bond to the triple bond to produce stereodefined alkenylalanes. The hydroalumination of alkynes is more limited in scope than the corresponding hydroboration reaction of alkynes (see Chapter 5) with regard to accommodation of functional groups and regioselectivity. Whereas hydroalumination of 1-alkynes is highly regioselective, placing the aluminum at the terminal position of the triple bond, unsymmetrically substituted alkynes produce mixtures of isomeric alkenylalanes. 

Hydroalumination of nonterminal olefins may be accompanied by isomerization to the terminal olefins, depending on the Al—H Ti ratio . The tetraalkylaluminates accessible via reaction (e) or (f) are useful in organic synthesis " . 

In donor solvents (EtjO, THF, RjN) the rate of hydroalumination is slower than with hydrocarbons. Nickel compounds catalyze the reaction, but isomerization may take place more readily. The regiospecificity of cis-hydroalumination of 1,2-disubstituted acetylenes with i-BujAlH is inferior to dialkylboranes (see 5.3.2.5.1) ... 

The submitters report that Z-4-(trimethylsilyl)-3-buten-l-ol of >98% isomeric purity can be obtained in ca. 60% overall yield by a more lengthy sequence involving hydroalumination-protonolysis of the tetrahydropyranyl (THP) ether of 4-(trimethylsilyl)-3-butyn-l-ol followed by cleavage5 of the THP ether with pyrldinium p-toluenesulfonate in methanol. This sequence is less convenient for the tetrahydropyridine synthesis described In the next procedure, since the Isomeric purity of the vlnylsilane is not Important for the cycllzatlon reaction.6... 

In contrast to the reaction with diisobutylaluminium hydride, hydroalumination of disubstituted alkynes with lithium hydridodiisobutylmethylaluminate, obtained from diisobutylaluminium hydride and methyllithium, results in anti addition across the triple bond. Subsequent reaction with aldehydes gives allylic alcohols, with CO2 gives a,p-unsaturated acids and with iodine gives alkenyl iodides, isomeric with the products obtained in the reaction sequences using diisobutylalvmiinium hydride. ... 

A valuable method for the synthesis of isomerically pure a/5-unsaturated nitriles via the hydroalumination of alkynes has been reported by Zweifel, Snow and Whitney [107]. Addition of di-isobutylaluminium hydride to an alkyne gives the trans-vinylalane (33) in 90% yield. Compound (33) does not react with cyanogen at room temperature but gives the vinylalanate (34) with methyl lithium. The latter reacts with cyanogen to given the trans-a,i3-unsaturated nitrile. 

Cp2ZrH(Cl) = ([Zr]-H) reacts with unsaturated C—C bonds to give isolable addition products (in opposition to boranes and alanes, organo-Zr are rather stable in dry air) that can be hydrolyzed with diluted acidic solutions. The scope of hydrozirconation with respect to chemoselectivity and substrate structure lies between those of hydroalumination and hydroboration. The facile isomerization of secondary alkylzirconium derivatives into primary alkyl derivatives occurs very readily (even below room temperature, note the difference with A1 and B ). 

Let s start with a synthesis of racemic S-deoxy-VGEi (90) developed by the Sih group at the University of Wisconsin. The key reaction was the addition of vinyllithium 88 to the THP ether derived from enone 86. The vinyllithium reagent was prepared by hydroalumination-iodination of I-octyne (87) followed by a transmetallation. Enone 86 was prepared in two steps from cyclopentadiene and ethyl 7-bromoheptanoate. Notice that the alkylation of lithium cyclopentadienide with this bromoester provided I-substituted cyclopentadiene 84 in quantitative yield. The isomerization that had to be avoided in the Corey lactone approach was a necessary part of these tactics. 

Terminal olefins may be converted to the a,p-unsaturated acid bearing one more carbon by hydroalumination followed by treatment with C02 9 Hydro-alumination of disubstituted acetylenes followed by carbonation can be controlled so as to produce isomerically pure cis- or trans-a, 3 -unsaturated acids39. 

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