Catalytic enantioselective methylation

TABLE 8B2.8. Catalytic, Enantioselective methyl acetate aldol addition reactions (Eq. 8B2.17)0... 

The stereoselectivity of the methylation of ketone enolates is determined by the structure of the substrate. Stereoselective methylation of cyclic ketone enolates has been examined in detail and current models reliably predict the stereochemical outcome (eqs 9-11). Diastereoselective methylation of acyclic ketone and ester enolates has been accomplished employing a variety of chiral auxiliaries (eq 12). Efficient catalytic enantioselective methylation of 6,7-dichloro-5-methoxy-l-indanone has been accomplished via a chiral phase-transfer catalyst (eq 13). An enantiomeric excess of 92% was observed when employing Chloromethane as the methylating agent, whereas... 

The interest in chiral titanium(IV) complexes as catalysts for reactions of carbonyl compounds has, e.g., been the application of BINOL-titanium(IV) complexes for ene reactions [8, 19]. In the field of catalytic enantioselective cycloaddition reactions, methyl glyoxylate 4b reacts with isoprene 5b catalyzed by BINOL-TiX2 20 to give the cycloaddition product 6c and the ene product 7b in 1 4 ratio enantio-selectivity is excellent - 97% ee for the cycloaddition product (Scheme 4.19) [28]. 

Combining catalytic enantioselective hydroboration (see p. 342) with animation has provided certain amines with good enantioselectivity. In this procedure the catechol group is replaced by methyl prior to the animation step. 

Catalytic enantioselective nucleophilic addition of nitroalkanes to electron-deficient alke-nes is a challenging area in organic synthesis. The use of cinchona alkaloids as chiral catalysts has been studied for many years. Asymmetric induction in the Michael addition of nitroalkanes to enones has been carried out with various chiral bases. Wynberg and coworkers have used various alkaloids and their derivatives, but the enantiomeric excess (ee) is generally low (up to 20%).199 The Michael addition of methyl vinyl ketone to 2-nitrocycloalkanes catalyzed by the cinchona alkaloid cinchonine affords adducts in high yields in up to 60% ee (Eq. 4.137).200... 

More recently, Maruoka and co-workers have reported several new phase-transfer catalysts one of which incorporates a morpholine ring as part of an azoniaspirocyclic core 161 <2007TL4675>. These were employed in the catalytic enantioselective conjugate addition of a-benzylcyanoacetate to acetylenic methyl ketone under phase transfer conditions. 

Very recently, a catalytic enantioselective route to prostaglandin i methyl ester was developed based on a tandem 1,4-addition-aldol reaction [84]. 

Corey reported a catalytic enantioselective cyanosilylation of methyl ketones using combination of a chiral oxazaborolidinium and an achiral phosphine oxide, [Eq. (13.23)]. An intermolecular dual activation of a substrate by boron and TMSCN by the achiral phosphine oxide (MePh2PO) is proposed as a transition-state model (54). The same catalyst was also used for cyanosilylation of aldehydes ... 

Stoichiometric amount of methyl aluminum p-binaphthoxide as the Lewis acid. This reaction has recently been extended to a catalytic enantioselective version using an enantiopure methylaluminum p-binaphthoxide (Scheme 11.59) (210,211). Although the actual reacting species were not assigned, 5-alkoxyoxazoles behave as nitrile ylide 1,3-dipole equivalents in Lewis acid catalyzed reactions with aldehydes. 

Quallich and Woodall described the first asymmetric synthesis utilizing a catalytic enantioselective reduction of the ketoester 35 with (S)-terahydro-l-methyl-3,3-diphenyl-lH,3W-pyrrolo[l,2-c][l,3.2]oxazaborole (CBS) to give the desired hydroxyester 36 (90% ee). After mesylation, Sn2 displacement with a higher-order cuprate derived from copper cyanide gave the diaryl r-butyl ester 37 with good chirality transfer. Intramolecular Friedel-Crafts cyclization gave the tetralone 31 in 90% ee (Scheme 7). ... 

In 1997, the first truly catalytic enantioselective Mannich reactions of imines with silicon enolates using a novel zirconium catalyst was reported [9, 10]. To solve the above problems, various metal salts were first screened in achiral reactions of imines with silylated nucleophiles, and then, a chiral Lewis acid based on Zr(IV) was designed. On the other hand, as for the problem of the conformation of the imine-Lewis acid complex, utilization of a bidentate chelation was planned imines prepared from 2-aminophenol were used [(Eq. (1)]. This moiety was readily removed after reactions under oxidative conditions. Imines derived from heterocyclic aldehydes worked well in this reaction, and good to high yields and enantiomeric excesses were attained. As for aliphatic aldehydes, similarly high levels of enantiomeric excesses were also obtained by using the imines prepared from the aldehydes and 2-amino-3-methylphenol. The present Mannich reactions were applied to the synthesis of chiral (3-amino alcohols from a-alkoxy enolates and imines [11], and anti-cc-methyl-p-amino acid derivatives from propionate enolates and imines [12] via diastereo- and enantioselective processes [(Eq. (2)]. Moreover, this catalyst system can be utilized in Mannich reactions using hydrazone derivatives [13] [(Eq. (3)] as well as the aza-Diels-Alder reaction [14-16], Strecker reaction [17-19], allylation of imines [20], etc. 

The first catalytic enantioselective trapping of benzene oxide-oxepine equilibrium mixture with an organometallic reagent is reported. The catalyst system included copper ditriflate and (llbi )-iV,./V-bis[(lR)-l-phenylethyl]di-naphtho[2,l- l, 2 -/][l,3,2]dioxaphosphepin-4-amine. The products of the reaction with dimethylzinc were (lA,65 )-6-methyl-2,4-cyclohexadien-l-ol in 93% ee and 4-methyl-2,5-cyclohexadien-l-ol <2001CC2606>. 

Inexpensive and readily available Grignard reagents and stable dinuclear Cu complexes have been used for the first time in catalytic enantioselective conjugate addition reactions to simple acyclic a -unsaturated methyl esters.95 These reactions have provided access to highly valuable -substituted chiral esters in good yields and with excellent enantioselectivities (up to 99% ee). 

Much work related to the development of a catalytic, enantioselective version of the Baylis-Hillman-Reaction by the use of chiral bases has been published. Only low enantiomeric excesses were obtained when brucin, N-methylprolinol, N-methyl-ephedrine and nicotine... 

Kobayashi S, Ishitani H (2000) Novel binuclear chiral zirconium catalysts used in enantioselective strecker reactions. Chirality 12 540-543 Kobayashi S, Ishitani H, Nagayama S (1995) Synthesis 1995 1195 Kobayashi S, Ishitani H, Ueno M (1998) J Am Chem Soc 120 431 Kobayashi S, Kobayashi J, Ishitani H, Ueno M (2002) Catalytic enantioselective addition of propionate units to imines an efficient synthesis of anti-alpha-methyl-beta-amino acid derivatives. Chem Eur J 8 4185 1190 Krohn K, Kirst HA, Maag H (eds) (1993) Antibiotics and antiviral compounds. VCH, Weinheim... 

Denmark et al. studied the effect of zinc iodide on the catalytic, enantioselective cyclopropanation of allylic alcohols with bis(iodomethyl)-zinc as the reagent and a bismethanesulfonamide as the catalyst 17]. They found significant rate enhancement and an increased enantiomeric excess of the product cyclopropane upon addition of 1 equivalent zinc iodide. Their studies and spectroscopic investigations showed that the Schlenk equilibrium appears to lie far on the left (IZnCHjI). Charette et al. used low temperature - C-NMR spectroscopy to differentiate several zinc-carbenoid species [18]. They also found evidence that in the presence of zinc iodide, bis(iodomethyl)zinc is rapidly converted to (io-domethyOzinc iodide. Solid-state structures of (halomethyl)zinc species have been described by Denmark for a bis(iodomethyl)zinc ether complex (6a) [19] and Charette for an (iodo-methyl)zinc iodide as a complex with 18-crown-6 (6b) [20] (Fig. 2). 

Carreira, E. M., Singer, R. A., Lee, W. Catalytic, Enantioselective Aldol Additions with Methyl and Ethyl Acetate 0-Sllyl Enolates A Chiral Tridentate Chelate as a Ligand for Titanium(IV). J. Am. Chem. Soc. 1994, 116, 8837-8838. 

The simple chiral lithium alkoxide 5 was applied to the Michael reaction of methyl phenylacetate with methyl acrylate to give the corresponding adduct in 84% ee (Eq, (12.6)) [19]. The catalytic enantioselective Michael reaction was also effected by the chiral alkoxide 5. 

An example of a catalytic, enantioselective [3 + 2] cycloaddition is the formation of 2 from MCP and methyl acrylate. The stereochemical information in these nickel(0)-catalyzed reactions is introduced by employing dilTerent phosphanes and phosphites with a (l/, 45) menthyl substituent as modifying ligand. Enantiomeric excesses of up to 36% have been reported, as determined by gas chromatographic analysis of the 3-methylenecyclopentanemethanol produced upon reduction of ester 2. 

In 1979, Koga and coworkers disclosed the first practical example of a catalytic enantioselective Diels-Alder reaction [44] promoted by a Lewis acidic complex, presumed to be menthoxyaluminum dichloride (1), derived from menthol and ethylaluminum di chloride, whose structure remains undefined [45]. This complex catalyzed the cycloaddition of cyclopentadiene with acrolein, methyl acrylate, and methacrolein with enantioselectivities as high as 72% ee. Oxidation of 2 (predominantly exo) followed by recrystallization actually lowered the ee ... 

Hydroxyethyl (3-lactam derivative was synthesized using the present reactions (scheme 17). Isoxazolidine derivative 37, prepared via the catalytic enantioselective 1,3-dipolar cycloaddition, was treated with methoxymagnesium iodide (Evans et al. 1985) to give methyl ester 38. Reductive N-O bond cleavage and deprotection of... 

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