ZACA reaction

Zirconium-catalyzed asymmetric carboalumination of alkenes (ZACA reaction) 272... 

For the syntheses of a large number of deoxypolypropionates requiring a,o -diheterofunctional intermediates, a couple of novel protocols, that are complementary with the conventional protocol using so-called Roche ester, have been developed (Scheme 33).199,200 More recently, the combined use of the ZACA reaction and the lipase-catalyzed kinetic resolution via selective acetylation has been shown to be practically attractive for the synthesis of enantio-merically pure compounds that cannot be readily purified by ordinary chromatography or recrystallization199,201 (Scheme 34). 

Scheme 33 Efficient ZACA reaction-based protocol for the synthesis of o,w-diheterofunctional deoxypolypropionates.

Table 3 Natural products synthesized via ZACA reaction... 

Deoxypolypropionates, via ZACA reaction, 10, 273 13-Deoxyserratine, via Pauson-Khand reaction, 11, 360 2-Deoxy sugars, via rhodium(II)-catalyzed intramolecular nitrene C-H insertions, 10, 203-204 Deprotection reactions, by nucleophilic tellurium species,... 

Figure 8.12 Stereo- and enantioselective synthesis of (S,f ,f ,S,f ,S)-4,6,8,10,16,18-hexa-methyldocosane via iterative zirconium-catalyzed asymmetric carboalumination of alkenes (ZACA reaction).

Zirconium-Catalyzed Asymmetric Carboalumination of Alkenes (ZACA Reaction)... 

Current Summary of Development and Application of the ZACA Reaction and Conclusion... 

Scheme 3.94 An efficient and general route to deoxypolypropionates by ZACA reaction [314].

For the synthesis of a,(o-diheterofunctional deoxypolypropionates, silyl-protected 2-methyl-4-penten-l-ols were initially prepared in four steps from the so-caUed Roche ester [244]. However, a couple of more efHcient and potentially economical protocols based on the ZACA reaction of styrene [30] and aUyl alcohol [164] have been developed, as shown in Scheme 3.96 and Scheme 3.97. 

In addition, the Pd-catalyzed cross-coupHng reactions of compound 46 obtained from ZACA reaction of allyl alcohol have been applied to the syntheses of differently substituted alkenyl, aryl, trimethylsilylethynyl, benzyl, and acyl halides in high yields, as shown in Scheme 3.98 [164]. 

Table 3.24 Natural products and related compounds of biological and medicinal interest synthesized via the ZACA reaction by the authors group.

Instead of MesAl, DIBAH-derived alkylaluminums via hydroalumination of alkenes were also applicable (Equation 60) [68]. 1-Decene is converted into n-decylaluminum (142) and subjected to ZACA reaction in the presence of isobuty-laluminum oxide (IBAO) to afford the corresponding optically active compound (143). 

The ZACA reaction of allyl alcohol with Me3Al afforded iodoalcohol (144) in good yield and enantioselectivity (Equation 61) [69]. The enantiopurity of (144) could be further improved by a combination with lipase-mediated reaction to provide useful chiral synthons (145) and (146) in high enantiopurity (Equations 62 and 63). 

The carbometalation reaction has been reviewed recently [28-30]. Negishi has demonstrated that zirconium(TV) complexes catalyze the carboalumination of MesAl to various alkynes and enynes [31]. Also the Zr-catalyzed asymmetric carboalumination of aUcenes (ZACA reaction) [32-34] has found important applications in the synthesis of natural products [35-37]. Especially efficient was the asymmetric synthesis of insect pheromones such as (S. / ./ ,S. / ,S)-4,6,8,10,16,18-hexamethyl-docosane (88) (Scheme 8) [38]. 

The carboalumination of terminal olefins with MeaAl in the presence of chiral zirconium catalysts [bis(l-neomenthylindenyl)zirconium dichloride, bis (l-neo- so-menthyl-4,5,6,7-tetrahydroindenyl)zirconium dichloride and so on], ZACA reaction, followed by oxidation of the chiral alanes is suitable for preparing optically active alcohols with high enantioselectivity [82] (Scheme 12). 

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