Asymmetric reactions carboalumination

Although the application of carboalumination to the synthesis of natural products is still in its infancy, a few preliminary results shown in Scheme 1.50 [167,168,171,172] suggest that it promises to become a major asymmetric synthetic reaction, provided that (i) the singularly important case of methylalumination can be made to proceed with S90% ee, and (ii) satisfactory and convenient methods for enantiomeric and diastereo-meric separation/purification can be developed. In this context, significant increases in ee in the synthesis of methyl-substituted alkanols from around 75 % to 90—93 % achieved through some strategic modifications are noteworthy (Scheme 1.50) [168]. Shortly before the discovery of the Zr-catalyzed enantioselective carboalumination, a fundamentally discrete Zr-catalyzed asymmetric reaction of allylically heterosubstituted alkenes proceeding via cyclic carbozirconation was reported, as discussed later in this section. 

Allyl aryl ethers undergo accelerated Claisen and [1,3] rearrangements in the presence of a mixture of trialkylalanes and water or aluminoxanes. The addition of stoichiometric quantities of water accelerates both the trimethylaluminum-mediated aromatic Claisen reaction and the chiral zirconocene-catalyzed asymmetric carboalumination of terminal alkenes. These two reactions occur in tandem and, after oxidative quenching of the intermediate trialkylalane, result in the selective formation of two new C-C bonds and one C-0 bond (Eq. 12.70).153 Antibodies have also been developed to catalyze Claisen154 and oxy-Cope155 rearrangements. 

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

All of the reactions discussed above are cyclic carbometallation reactions of metallacycles. Very recently, an interesting Cr-catalyzed carboalumination of propargyl derivatives producing allenes via a carbometallation-elimina-tion sequence has been studied. This reaction provides an asymmetric synthesis of chiral allenes (Scheme 57). 

Asymmetric amplification, in diisopropylzinc additions, 2, 386 Asymmetric arylation, phenols with lead triacetates, 9, 399 Asymmetric carboalumination, Zr-catalyzed, alkenes, 10, 272 Asymmetric carbonyl-ene reaction, characteristics, 10, 559 Asymmetric catalysis... 

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)... 

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]. 

Negishi coupling reactions can be combined with asymmetric carboalumination, a process that was also discovered by the Negishi group (Scheme 5-87). The asymmetric induction of this zirconium-catalyzed enantioselective methylalumination process ( ZACA ) stems from a chiral zirconium catalyst precursor, namely dichlorobis(neomenthylindenyl)zirconium [(NM aZrCb]. The stereoinduction is very high. 

Although they are not natural product syntheses, the reactions shown in Scheme 31 are noteworthy because they involve the Zr-catalyzed asymmetric carboalumination of allylic ethers [200,201]. In marked contrast with the Zr-catalyzed asymmetric ethylmagnesation and related reactions of allylically het-erosubstituted alkenes discussed in Sect. 6.1.1, the corresponding cases of the Zr-catalyzed asymmetric carboalumination have often been problematic. 

This book is presented as a volume of Topics in Organometallic Chemistry, aiming at giving an overview of the chemistry of metallocenes. In particular, in this book we focused on, (i) hydrozirconation and its application to natural product synthesis, (ii) the asymmetric carboalumination reaction, (iii) the cyclization reaction using metallocenes, (iv) catalytic reactions using metallocenes, (v) olefin polymerization and (vi) carbon-carbon bond cleavage reactions using metallocenes. I would like to express my thanks to all contributors to this book. 

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