Quaternary chiral centers

The asymmetric synthesis of a galanthamine alkaloid relies also on the intramolecular Heck reaction for the preparation of the benzo[h]furan-based key intermediate with a crucial chiral quaternary center, which eventually leads to the synthesis of (-)-galanthamine <00JA11262>. A similar approach towards the construction of galanthamine ring system via an intramolecular Heck reaction has also been investigated <00SL1163>. 

Larry Overman also used (J. Am. Chem. Soc. 2004,126, 14043) a chiral pool starting material, but in a different way. The prochiral enolate 12 showed substantial diastereoselectivity in its reaction with the bis-triflate 13, almost 10 1. Through the power of algebra, it followed that the three diastereomers of 14 were formed in a ratio of 90 9 1. The crystalline 14 was easily isolated in diastereomerically-pure form, and carried on to phenserine 15. This is a new method for the stereocontrolled construction of chiral quaternary centers. 

Chiral 3,3-disubstituted cyclopentanones. Taber et al have extended a synthesis of cyclopentanones by a rhodium catalyzed intramolecular C—H insertion (11,459) to a synthesis of (+ )-a-cuparenone (3), which contains a chiral quaternary center. Thus the chiral a-diazo-p-keto ester 1, prepared by alkylation of a chiral oxazolidone (11, 379-381) on treatment with Rh2(OAc)4 is converted into 2 in 67% yield. This product is converted in several steps into (+ )-3. 

Interestingly, this substitution reaction can be applied to the stereoselective assembly of chiral quaternary centers and has been extended to the preparation of chiral tertiary alcohols via a stereoselective Baeyer-Villiger rearrangement, and chiral tertiary amines via a stereoselective Curtius rearrangement (Scheme 15)130>130a... 

The use of 1 for the preparation of a chiral quaternary center via asymmetric alkylation has also been investigated. Although 1 has proven to be an effective reagent for the enantioselective generation of tertiary centers, its use for generating quaternary centers has been of only marginal use (eq 6). However, other chiral tetradentate amines can be used for this purpose. ... 

The reaction of a wide variety of functionalized epoxides containing esters, amides and acetals with chlorotitanium triphenoxide and allylmagnesium chloride provides exclusive reaction at the more substituted carbon <05T6726>. The use of protected chiral epoxides, 54 and 56, with the same reagent system provides a facile route into chiral quaternary centers, 55 and 57. 

Keywords Chiral quaternary center Oxindole Spirooxindole... 

Elaboration of isoquinoline derivatives in asymmetric fashion was examined as well in 2001. In a manner similar to that described in section 6.1.3.2, an enantioselective Reissert-type reaction was utilized to construct a chiral, quaternary center at the Cl position of isoquinoline derivatives. For example, treatment of isoquinoline 85 with vinyl chloroformate and TMSCN in the presence of bifunctional catalyst 86 afforded isoquinoline derivatives such as 87 in up to 95% ee. The effect of the R group at the 1-position and the catalyst counterion were detailed. 

A catalytic asymmetric isatin-involved Povarov reaction was utilized by Shi and colleagues to prepare 251 in a diastereo- and enantioselective manner. During the three-component coupling, two chiral quaternary centers are formed in >99 1 dr and up to 97% ee (130L128). Complex polyhet-erocyclics 252 and 253 were prepared by a highly selective four-component domino multicyclization with an isatin, an enamineone, and two acetylenes. Four new rings and four stereocenters are created in a one-pot operation, with the reactions complete within 30 min in up to 64% yield (13OL1540). 

Terrasson, V, van der Lee, A., de Figueiredo, R. M., Campagne, J.-M. (2010). Organocatalyzed cyclopropanation of alpha-substituted alpha.beta-unsaturated aldehydes enantioselective synthesis of cyclopropanes bearing a chiral quaternary center. Chemistry - A European Journal, 16,7875-7880. 

The formation and control of chiral quaternary centers by multicomponent reactions is undoubtedly a challenging task. The combination of a carbometalation reaction of chiral alkynyl sulfoxide 33, followed by a zinc homologation and an allylation in a four-component process, allowed the preparation of homoallylic alcohols or amines 34 bearing tertiary and quaternary stereocenters in a single step with high yields and diastereoselectivities (Scheme 11.13). The zinc carbenoid used in this reaction can be prepared independently or in situ by the reaction of diethyl zinc and diiodomethane. This carbenoid readily homologates the vinyl copper into the allylic species, which reacted diastereoselectively with aldehydes, to give the expected products. The chiral sulfinyl moiety can be easily removed by treatment with alkyllithi-ums, which allows a further functionalization of the carbon skeleton [35]. 

Skule, G., Marek, I. (2006). New multicomponent approach for the creation of chiral quaternary centers in the carbonyl aUylation reactions. Journal of the American Chemical Society, 128, 4642-4649. 

The asymmetric allylation reaction offers a very easy access to chiral quaternary centers. The first example of catalytic asymmetric alkylations of a-substituted -keto esters using 1 in the presence of pocket ligand (l/f,2/f)-his[(diphenylphosphino)-benzamido]cyclohexane in high selectivity has been reported. The tetralone system showed high selectivity, with the allylated... 

Intramolecular trapping of Pd(II)-jj -aUyl intermediates by nucleophiles such as phenols is possible, a transformation exemplified by reaction of Pd(0)/(5, 5)-Trost ligand with phenol allyl carbonates 29, which brings about the construction of chiral quaternary centers and the formation of chiral chromans 30 (eq 20). ... 

The stmcture of the target conqiound is sinq)le and the only synfiietic challenge is presented by file presence of a chiral quaternary center. Retrosynthetically, 1 can be derived firom a chiral a-methyl amino acid (2), which belongs to a class of confounds which is readily available by a nuniber of approaches.[5] The discovery route (Scheme 1) did not seek to address enantioselectivity and relied instead on chromatographic resolution to separate BIRT 377 firom its distomer. 

Welwitindolinone A Isonitrile 3 is the first of a family of oxindole natural products isolated from the cyanobacteria Hapalosiphon welwischii and Westiella intricate on the basis of their activity for reversing multiple drug resistance (MDR). A key transformation in the total synthesis of 3 reported (J. Am. Chem. Soc. 2008,130, 2087) by John L. Wood, now at Colorado State University, was the chlorination of 1, that in one step established both the axial secondary chloro substituent and the flanking chiral quaternary center. 

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