Functionalization enantioselective asymmetric addition

Related catalytic enantioselective processes It is worthy of note that the powerful Ti-catalyzed asymmetric epoxidation procedure of Sharpless [27] is often used in the preparation of optically pure acyclic allylic alcohols through the catalytic kinetic resolution of easily accessible racemic mixtures [28]. When the catalytic epoxidation is applied to cyclic allylic substrates, reaction rates are retarded and lower levels of enantioselectivity are observed. Ru-catalyzed asymmetric hydrogenation has been employed by Noyori to effect the resolution of five- and six-membered allylic carbinols [29] in this instance, as with the Ti-catalyzed procedure, the presence of an unprotected hydroxyl function is required. Perhaps the most efficient general procedure for the enantioselective synthesis of this class of cyclic allylic ethers is that recently developed by Trost and co-workers, involving Pd-catalyzed asymmetric additions of alkoxides to allylic esters [30]. 

A recent application of enantioselective conjugate radical additions was seen in the synthesis of (+)-ricciocarpins A and B [95]. The key step in the synthesis was an asymmetric addition of a functionalized radical precursor 141 to afford intermediate 142 (Scheme 37). A chiral catalyst screening revealed that Mgt and bisoxazoline ligand 19 was optimal for achieving... 

Since the pioneering studies of asymmetric catalysis with core-functionalized dendrimers reported by Brunner (88) and Bolm (89), several noteworthy investigations have been described in this field. Some examples of the dendritic effects observed in enantioselective catalysis with dendrimers having active sites in the core were discussed in Section II, such as the catalytic experiments with TADDOL-cored dendrimers described by Seebach et al. (59) the asymmetric addition of Et2Zn to aldehydes catalyzed by core-functionalized phenylacetylene-containing dendrimers reported by Hu et al (42)-, the asymmetric hydrogenation investigations with (R)-BINAP core-functionalized dendrimers synthesized by Fan et al. (36) or the results... 

Asymmetric addition of functionalized allylic nucleophiles is also a useful process. Yoshito Kishi of Harvard University has shown (J. Am Chem. Soc. 2004,126. 12248) that 2,3-dibromopropene 4 will add with high enantioselectivity to linear and branched aliphatic aldehydes. The analogous Cl and I derivatives can also be prepared, using the same approach. 

Enantioselective Michael addition of glycine derivatives by means of chiral phase-transfer catalysis has been developed to synthesize various functionalized a-alkyl-a-amino acids. Corey utilized 4d as catalyst for asymmetric Michael addition of glycinate Schiff base 1 to a,(3-unsaturated carbonyl substrates with high enantioselectivity (Scheme 2.15) [35,36]. With methyl acrylate as an acceptor, the a-tert-butyl-y-methyl ester of (S)-glutamic acid can be produced, a functionalized glutamic acid... 

The first catalytic asymmetric addition of functionalized organozinc reagents to ketones has been reported.107 These investigations indicated that catalyst (40) is tol- erant to a variety of functionalized zinc reagents and enantioselectivities generally exceed 90%. 

Enantioselective Michael addition of glycine derivatives by means of chiral phase-transfer catalysis has been developed to synthesize various functionalized a-alkyl-amino acids. Corey and colleagues utilized 30d as a catalyst for the asymmetric... 

Reagents of this type are suitable for performing catalytic asymmetric additions to aldehydes. For example, an enantiomerically pure Lewis acid is generated in situ from Ti(OiPr)4 and the enantiomerically pure bis(sulfonamide) C. It catalyzes the enantioselective addition of functionalized (or unfunctionalized) dialkylzinc compounds to widely variable aldehydes. There is no detailed, substantiated rationalization of the underlying addition mechanism in this case. 

Enantioselective carbonyl addition of dialkylzinc reagents to aldehydes is one of the most important and fundamental asymmetric reactions [2,15]. Several chiral titanium complexes have been developed to accelerate this type of reaction (Sch. 3) [16,18-26] since Ohno and Kobayashi achieved high enantioselectivity in the presence of Ti(OPr )4 and chiral disulfonylamide [16,17]. Seebach has also demonstrated that TADDOL-derived titanium complexes function as efficient asymmetric catalysts [18]. 

The transition metal catalyzed asymmetric addition of aryl organometallic reagents to aldehydes, ketones, and imines has provided efficient access to chiral aryl alcohols or aryl amines [89]. Arylboronic acids are less toxic, stable toward air and moisture, and tolerant towards a variety of functional groups, and are ideal reagents for the addition to aldehydes. However, when Sakai et al. [90] attempted the enantioselective Rh-catalyzed addition of phenylboronic acid to naphthaldehyde, only 41% ee was obtained. Chiral spiro phosphite complex (S)-18c was found to be an efficient catalyst for asymmetric addition reactions of arylboronic acids to aldehydes, providing diarylmethanols in excellent yields (88-98%) with up to 87% ee (Scheme 30) [20c]. 

In the area of enantioselective synthesis see Enantio selectivit ), the development of catalytic carbon-carbon bond-forming reactions that proceed under mild conditions in an enantioselective fashion (ee > 95%) remains a challenging objective.Among a great variety of metallic complexes, Zr-containing chiral catalysts can promote efficient and highly enantioselective additions of nucleophilic fragments such as alkylmetals and cyanides to C=0 and C=N bonds. Moreover, Zr-based metallocenes promote additions of alkylmetals to carbon-carbon double bonds, reactions that do not easily occur with other catalysts. One another important feature is that the product of the asymmetric addition of an alkylmetal to an alkene produces a chiral alkylmetal that can be further functionalized. 

Modern aspects of electrophilic aromatic substitution chemistry address the development of enantioselective variants of these direct (hetero)arene functionalization reactions. For example, enantiomerically enriched metal catalysts, as well as organocatalysts, allowed for the asymmetric addition reactions of (hetero)arenes onto (a,P-unsaturated) carbonyl compounds. Additionally, highly enantioselective arylations of carbonyl compounds were accomplished with organometallic reagents... 

The Mannich reaction and its variants have been reviewed, mainly focussing on asymmetric catalysis thereof. Catalytic, enantioselective, vinylogous Mannich reactions have also been reviewed, covering both direct and silyl dienolate methods. Another review surveys Mannich-type reactions of nitrones, oximes, and hydrazones. A pyrrolidine-thiourea-tertiary amine catalyses asymmetric Mannich reaction of N-Boc-imines (e.g. Ph-Ch=N-Boc) with ethyl-4-chloro-3-oxobutanoate to give highly functionalized product (16). Addition of triethylamine leads to one-pot intramolecular cyclization to give an 0-ethyl tetronic acid derivative (17). ... 

Significant counterion effects are observed in the enantioselectivity of addition of diethylzinc to benzaldehyde using a titanium/a-acetyl-(5 )-BINOL system. rran5-l,2-Diaminocyclohexane - a common motif used in asymmetric catalysis - exhibits a dihedral angle of ca 60° between the amino groups, whereas rranx-ll,12-diamino-9,10-dihydro-9,10-ethanoanthracene (124) is constrained to >110°. Further functionality and chirality has been incorporated by the formation of bis-sulfonamides of (124), using (S j-camphor sulfonyl chloride. The... 

Recently, Woodward s group [22] reported that bis-sulfamoyl imines are potentially ideal substrates for the Rh-catalyzed asymmetric additions of boronic acids because of (i) near-perfect enantioselectivities (11 examples, 98% to 99% ee), (ii) good-to-excellent diastereoselectivities (10-32 1 r c/meso )> and (iii) high functional group tolerance in the removal of the protecting group via mild heating in aqueous pyridine (Scheme 6.17). 

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