Stereogenic quaternary

The asymmetric arylation of ketone enolates represents an attractive method for the preparation of optically active carbonyl compounds with a stereogenic quaternary center at the a-position to the carbonyl group. Such types of compounds are important intermediates for natural product synthesis. Replacement of BINAP by 109 provides... 

The a-cyanoacetates 12 are optimal substrates for the approach outlined in Scheme 2.26 due to the low pKa of the a-proton. It has been reported that the quinidine-derived alkaloid /fisocupridine (/ -ICD) can catalyze the direct a-amination of a-cyanoacetates 12 (Eq. 4) and /fdicarbonyl compounds [10], probably by an enolate having a chiral /MCD-H+ counterion as the intermediate. The a-amination of a-cyanoacetates 12 with di-tert-butyl azodicarboxylate 2c is an efficient process that proceeds with only 0.5 mol% of /MCD. The expected products 13, having a stereogenic quaternary carbon center, were isolated in excellent yields and with excellent levels of enantioselectivity independently by the nature of the aryl-substituent in the a-cyanoacetates, while the / -dicarbonyl compounds give slightly lower enantioselectivty (83-90% ee). 

The direct enantioselective organocatalytic a-fluorination can also be performed with cinchona alkaloid derivatives as catalyst under phase-transfer reaction conditions [25]. The fluorination reaction by NFSI of / -ketoesters 21, readily enolizable substrates, generated a stereogenic quaternary C-F bond in high yields and with enantioselectivities up to 69% ee for the optically active products 26 (Eq. 6). 

Mortko, C.J. and Garcia-Garibay, M.A. (2006) Engineering stereospecific reactions in crystals synthesis of compounds with adjacent stereogenic quaternary centers by photodecarbonylation of crystalline ketones, in Topics in Stereochemistry, Vol. 25 (eds S.E. Denmark and J.S. Siegel), John Wiley Sons, Hoboken, NJ, pp. 205—253. 

Vuagnoux-d Augustin M, KeMi S, Alexakis A (2007) Enantioselective copper-catalyzed conjugate addition to 2- or 3-substituted cyclopent-2-en-l-ones construction of stereogenic quaternary carbon centers. Synlett 2057-2060... 

Several structural features of (-)-rhazinilam 3 raise interesting synthetic challenges the axially chiral phenyl-pyrrole A-C biaryl bond, the fused pyrrole-piperidine C-D rings, the stereogenic quaternary carbon (C-20) ortho to the phenyl-pyrrole axis, the nine-membered lactam firing. Three racemic (Smith, Sames, Magnus) and one asymmetric (Sames) total syntheses have been published to date, which all proceed via construction of the pyrrole ring and diastereoselective control of the axial chirality by the central chirality at C-20. 

As illustrated in Scheme 10, the CAB catalyst also effectively catalyzes the intramolecular Diels-Alder reaction of trienal 8 to afford bicyclic product 9 in high diastereo- and enantioselectivity [58]. In a single step, this endo-selective reaction achieves the formation of a tetrahydroindane ring system containing a stereogenic quaternary center. 

Overman LE, Larrow JF, Steams BA, Vance JM (2000) Enantioselective Constmction of Vicinal Stereogenic Quaternary Centers by Dialkylation Practical Total Syntheses of (-i-)-and meso-Chimonanthine. Angew Chem Int Ed 39 213... 

Vickers and Keay [58] generated a stereogenic quaternary centre through intramolecular Mizoroki-Heck reaction in excellent yield. However, they obtained a 1 1 mixture of the two possible regioisomers (Scheme 6.13). 

ShibasaM and coworkers [117] described the first enantioselective combination of this type in their synthesis of the natural product halenaquinone (225) possessing antibiotic, cardiotonic and protein tyrosine kinase inhibitory activities. The key step is an intermolecular Suzuki reaction of 222 and 223 followed by an enantioselective Mizoroki-Heck reaction in the presence of (5 )-BINAP to construct the third ring and the stereogenic quaternary centre present in 224. The reaction proceeded with a good cc-value of 85% but with a yield of only 20% (Scheme 8.56). 

Overman, L.E., Paone, D.V. and Stearns, B.A. (1999) Direct stereo- and enantiocontroUed synthesis of vicinal stereogenic quaternary carbon centers. Total syntheses of meso- and (—)-chimonanthine and (-l-)-calycanthine. J. Am. Chem. Soc., 121, 7702-3. 

Deng et al. have reported the use of simple cupreines such as 127 as efQcient organocatalysts for the construction of stereogenic quaternary centers through the conjugate addition of a-substituted P-ketoesters to a,P-unsaturated ketones [218], The reaction affords excellent yields as well as diastereo-, and enantioselectivities... 

Other examples of shown effectiveness of PTCs were reported by Park, Jew, and co-workers [98], They developed enantioselective synthetic method for the preparation of (/ )-a-alkylserines and (S)-a-alkylserines based on asymmetric alkylation of phenyl or o-biphenyl oxazoUne derivatives using CBPTC XXXXVIa and binaphthol-derived Maruoka s catalyst XXV, respectively (Scheme 8.16). The same authors [99] also expanded this methodology to enantioselective synthesis of (/ )-a-alkylcysteines and (5)-a-alkylcysteines using thiazoline-4-carboxylates in PTC alkylation. In 2006, Maruoka and co-workers [100] reported first example of the catalytic asymmetric alkylation of glycolates that establishes stereogenic quaternary carbon centers (Scheme 8.17). Their approach utilized 3,5-diaryloxazolidin-2,4-diones 48 as novel... 

During a synthesis of ( )-albene 133, an orthoester rearrangement allowed the control in the formation of a stereogenic quaternary center in a bicyclo[2.2.1]hep-tane alcohol derivative. In this synthesis [31], Srikishna prepared the aUyUc alcohol 134 by a Diels-Alder cycloaddition followed by several transformations. Alcohol 134 afforded by rearrangement the ester 135 via a sterically preferred exo transition state (Scheme 6.19). 

The antitumor polyhalogenated compound halomon 290 is extracted from a red alga. Mioskowski [65] described an efficient synthesis of this intriguing compound. One of the key steps of the synthesis, a Claisen-Johnson rearrangement, afforded ester 293 allowing the introduction the stereogenic quaternary center (Scheme 6.46). 

Lemieux and Meyers have used a chiral bicyclic thiolactam to produce vicinal stereogenic quaternary centers, as in the sesquiterpene (-)-trichodiene [158]. A single diastereoisomer was formed during this process (Scheme 9.35). Surpris-... 

Asymmetric addition of arylboroxines to cyclic N-sulfonylimines 92 or arylborates to iV-sulfonylimines 95 in the presence of a newly developed rhodium catalyst 93 coordinated with a sulfur-olefin ligand (L ) is a facile method to obtain benzosultams 94 or 97, wherein a stereogenic quaternary... 

Resendiz MJ, Family F, Fuller K, Campos LM, Khan SI, Lebedeva NV, Forbes MD, Garcia-Garibay MA. Radical reactions with double memory of chirality (2MOC) for the enantiospecific synthesis of adjacent stereogenic quaternary centers in solution cleavage and bonding faster than radical rotation. J. Am. Chem. Soc. 2009 131(24) 8425-8433. 

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