Aluminum alkoxides chiral

HI. CHIRAL TRICOORDINATE ALUMINUM REAGENTS A. Aluminum Alkoxides and Derivatives... 

Early studies of the asymmetric reduction of prochiral ketones by chiral aluminum alkoxides have been reviewed by Morrison and Mosher (1). Doering and Young (123) reported the reduction of methyl cyclohexyl ketone with chiral 3-methyl-2-butanol in the presence of a catalytic amount of aluminum alkoxide to give the (S)-( + )-carbinol in a 22% optical yield. Jackman and co-workers (124) similarly reduced methyl n-hexyl ketone with chiral 3,3-dimethyl-2-butanol to the (S)-( - )-carbinol in a 6% optical yield. Other attempts resulted in similar low optical yields or gave only racemic products. Since the reductions were carried out under equilibrium conditions, racemization could have accounted for the low optical yields. 

Modified MPV-type reductions carried out with chiral magnesium alkoxides and with chiral Grignard reagents have been discussed in detail (1). These reagents differ from the aluminum alkoxides since the Grignard reaction is essentially irreversible. Chiral alkali metal alkoxides have also been used to effect asymmetric reductions (1). 

Ring-opening polymerization of racemic iV-carboxyamino acid anhydrides can be achieved with a chirally modified aluminum alkoxide (180). 

Enantiomer-selective polymerization of MBMA has also been attained by using the reaction products of chiral amine compounds, 168 and 169, with cyclohexylmagnesium bromide as initiator [242,243] and by using the aluminum porphyrin complex 170 in the presence of optically active aluminum alkoxide compounds 171a-e [244], In the latter systems, the enantiomer selection is based on enantiomer-selective coordination of the chiral aluminum compounds to MBMA as revealed by NMR analysis. With 171e as a catalyst, the ee of the unreacted monomer is 40% at 75% monomer conversion ratio in the polymerization at -70°C. 

The earliest report of a reaction mediated by a chiral three coordinate aluminum species describes an asymmetric Meerwein-Poimdorf-Verley reduction of ketones with chiral aluminum alkoxides which resulted in low induction in the alcohol products [1]. Subsequent developments in the area were sparse until over a decade later when chiral aluminum Lewis acids began to be explored in polymerization reactions, with the first report describing the polymerization of benzofuran with catalysts prepared from and ethylaluminum dichloride and a variety of chiral compounds including /5-phenylalanine [2]. Curiously, these reports did not precipitate further studies at the time because the next development in the field did not occur until nearly two decades later when Hashimoto, Komeshima and Koga reported that a catalyst derived from ethylaluminum dichloride and menthol catalyzed the asymmetric Diels-Alder reaction shown in Sch. 1 [3,4]. This is especially curious because the discovery that a Diels-Alder reaction could be accelerated by aluminum chloride was known at the time the polymerization work appeared [5], Perhaps it was because of this long delay, that the report of this asymmetric catalytic Diels-Alder reaction was to become the inspiration for the dramatic increase in activity in this field that we have witnessed in the twenty years since its appearance. It is the intent of this review to present the development of the field of asymmetric catalytic synthesis with chiral aluminum Lewis acids that includes those reports that have appeared in the literature up to the end of 1998. This review will not cover polymerization reactions or supported reactions. The latter will appear in a separate chapter in this handbook. 

Construction of useful structural models for these reactions, however, would require not only a fiill structural characterization of the Lewis acid, but also knowledge of the preferred conformation of the chiral ligands. In many cases the catalysts are generated in situ and the stoichiometry or the aggregation state of the Lewis acid are not well deHned. The latter point is particularly important since both titanium and aluminum alkoxides are known to form dimeric or polymeric species. 

Asymmetric, borane-modified MPV reduction of a variety of aromatic ketones to their corresponding alcohols has recently (43) been reported using a chiral aluminum alkoxide catalyst shown in Figure 5. This compound was formed in situ from aluminum isopropoxide and (R)-l,r-binapthyl-diol in... 

Figure 5 Chiral aluminum alkoxide catalyst (From Ref 43).

Fu, l.-P. and Uang, B.-J., Enantioselective borane reduction of aromatic ketones catalyzed by chiral aluminum alkoxides. Tetrahedron Asymmetry, 12 1,45-48, 2001. Experimental- Al[OCH(CH3)2]3 was obtained from commercial manufacture (Oiat-tem Chemicals) and maintained in liquid form by storage at 85"C in a sealed can for >6 months. Double distilled A1[0(CH3)CH2CH2CH3]3 was used as supplied from commercial production (Chattem Chemicals). 70 30 wt% AlP/ASB was prepared from freshly made commercial aluminum isopropoxide and aluminum sec-butoxide. Tolu-... 

Haubenstock, H. Panchafingam, V. Odian, G Stereoelective polymerization of propylene oxide with a chiral aluminum alkoxide initiator. Makmmol. Chem. 1987,188, 2789-2799. 

Spassky, N. Wisniewski, M. Pluta, C. Le Borgne, A. Highly stereoelective polymerization of roc-(D,L)-lactide with a chiral Schiff s base/aluminum alkoxide initiator. Macromol. Chem. Phys. 1996, 197, 2627-2637. 

Chiral Schiff base/aluminum alkoxide The resultant rac-FLA had a gradient stereocopolymer structure and exhibited reinforced thermal stability due to a stereocomplex formation (Tm = 210°C) SCM [16]... 

An efficient enantioelective or enantioselective polymerization, based on single-site initiators of rac-LA, has been realized by Spassky and co-workers, who applied achiral and chiral aluminum alkoxides of general structure O2AI-OR, bearing Schiff base ligands. ... 

Aluminum alkoxide can be also used as a base. Chiral aluminum alkoxide prepared from Al(Oi-Pr)3 and BINOL mediated asymmetric desymmetrization of meso-cyclopentenone epoxide through p-eliminative ring-opening reaction to give hydroxylated cyclopentenone in 95% ee (Scheme 6.77) [97]. 

Pioneers in the asymmetric reduction area developed suitable reagents by modifying lithium aluminum hydride (LAH) (7) or by developing chiral versions of Meerwdn-Ponndorf-Verley reductions with chiral aluminum alkoxides (8) or chiral Giignard reductions with chiral alkyl magnesium halides (9). 

Preparation of Derivatives. Enoate derivatives are prepared from the corresponding chiral alcohol by treatment with acry-loyl chloride in the presence of Triethylamine and catalytic 4-Dimethylaminopyridine or the appropriate carboxylic acid chloride and Silveril) Cyanide. Alkynyl ethers are readily available from the potassium alkoxide by treating with Trichloroethylene, in situ dechlorination with n-Butyllithium, and electrophilic trapping. Trapping the intermediate anion with a proton source or lodomethane followed by Lindlar reduction of the alkynyl ether affords the corresponding vinyl and l-(Z)-propenyl ether, respectively, while reduction of the alkynyl ether with Lithium Aluminum Hydride affords the l-( )-propenyl ether. 

Assessment of the role of the cation in MPV reduction is difficult, Conversion of alcohol to alkoxide certainly enhances the reactivity towards hydride donation, and aluminum ions aid via chelation in arranging alkoxide and carbonyl compound properly for reaction. However, alkoxides bearing cations other than aluminum may also exhibit good hydride-donating tendencies. Lithium isopropoxide reduces steroidal ketones efficiently and magnesium alkoxides derived from chiral alcohols have been used extensively in chiral syntheses. Isobomyloxy magnesium bromide (52) has been used widely for this purpose (equation 27). ... 

Propylmagnesium bromide deprotonates several chiral alcohols (borneol, isoborneol, 1 -phenylethanol, p-methan-3-ol). These chiral magnesium alkoxides are used for asymmetric reduction of phenyl-trifluoromethylketone [32 Eq. (25)]. The magnesium alkoxides generally give poorer asymmetric induction than aluminum derivatives. 

The mechanistic complexities of stereoselectivity is further evidenced by a recent report by Maudoux et a/. who describe a chiral aluminum salen catalyst that generates highly isotactic PLA from rac-lactide (Pm-0.90). In this example, the kinetics indicated a dominant chain-end control mechanism, which contrasts to other chiral aluminum salen catalysts where enantiomorphic site control is thought to predomi-nate. ° All the previously mentioned chiral aluminum salen alkoxide systems require multiple days at elevated temperatures to polymerize -200 equiv. of lactide. The low activity of chiral aluminum salen systems towards lactide polymerization is a major drawback of these systems. 

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