Iodonium asymmetric

A similar procedure was employed in the asymmetric Heck-type coupling of iodonium salt 81 with 2,3-dihydrofuran (Scheme 38) [65]. When carried out in the presence of the chiral bidentate ligand (R)-BINAP, this reaction afforded optically active (up to 78% ee) coupling product 82 in moderate yield. 

Asymmetric phenylation of carbanions with chiral iodonium salts has recently been reported [70]. The chiral diiodonium salt 93 selectively reacts with potassium enolate of l-oxo-2-indancarboxylate 92 to give the a-phenylated indanone 94 with moderate enantioselectivity (Scheme 42). 

The metal-catalyzed carbenoid decomposition of iodonium ylides can be applied in asymmetric reactions [149-152]. For example, the copper(II)-cat-alyzed intramolecular C-H insertion of phenyliodonium ylide 209 in the presence of several chiral ligands affords product 210 (Scheme 74) [151]. Enantiose-lectivities in this reaction vary in the range of 38-72% for different chiral... 

The intermediate iodonium ion controls the relative stereochemistry of the cyclization. An asymmetric center present within the substrate, therefore, allows for enantioselectivity (cf. Scheme 22.12).51 The reaction is very susceptible to the steric interactions within the transition slate.48,59 53... 

The addition of iodine azide to 3-/ 7-butylcyclohexcnc in either acetonitrile or dichloromethane gave in moderate yields a mixture of, 2-trans-2,3-cis- and 1,2-trans-2f-trans- -azido-2-iodo-3-ferr-butylcyclohexane 1, with complete regio- and simple diastereoselectivity but moderate induced diastereoselectivity45 46. The stereochemical outcome is explained by assuming the reversible formation of asymmetric iodonium ions (cis and tram to f-Bu), and the preferential attack of azide ion on the cis iodonium ion (antiparallel to the axial allylic hydrogen)46. 

A chiral bisphosphine such as 2,2 -h -(diphenylphosphino)-l,F-binaphthyl (BINAP) has been extensively used as a chiral chelator in asymmetric catalysis. When Stang et al. reacted the chiral metal complex 42 with 40, they synthesized a square box (Figure 25) and asymmetric induction was observed [79,82] with the formation of an excess of one of the preferred diastereoisomers as measured by NMR spectroscopy. The same reaction has been carried out with 42 and 6is-4-(4 -pyridyl)phenyl)iodonium triflate, but in this case the diaza ligands of the iodonium species possess rotational symmetry about their linkages. Consequently, the optical activity of the molecular squares obtained is due exclusively to the chiral transition metal auxiliary BINAP. 

Aggarwal and Olofsson have developed a direct asymmetric a-arylation of prochiral ketones using chiral lithium amide bases and diaryliodonium salts [881]. In a representative example, the deprotonation of cyclohexanone derivative 684 using chiral Simpkins (/ ,/ )-base followed by reaction with the pyridyl iodonium salt gave the arylated product 685 in 94% ee (Scheme 3.275). This reaction has been employed in a short total synthesis of the alkaloid (-)-epibatidine [881]. 

Asymmetric a-functionalization of carbonyl compounds with iodine(lll) reagents is discussed in Chap. 639 and in a recent review [178], and is only briefly covered here. Asymmetric a-arylations with chiral diaryliodonium salts have proven to be difficult to achieve, both because of complicated synthetic routes to chiral, unsymmetric salts with suitable dummy groups, and because of the modest enantioselectivities observed in the arylations [188, 189]. Ochiai and coworkers reported the only successful example to date, where 1,1 -binaphthyl-derived iodonium salts gave chemo- and enantioselective arylation of p-ketoesters in up to 53% ee (see Scheme 7 in Chap. X) [190]. 

Stereoselective carbon-carbon bond formations with hypervalent iodine reagents are also prominently described in the literature. Direct asynunetric a-arylation reactions are not easy to perform. Ochiai et al. synthesized chiral diaryliodonium salts such as [l,l -binaphthalen]-2-yl(phenyl)iodonium tetrafluoroborate derivatives 21 via a BFs-catalyzed tin-X -iodane exchange reaction and developed the direct asymmetric a-phenylation of enolate anions derived from cyclic p-ketoesters (Scheme 7) [37]. A beautiful example of direct asymmetric a-arylation of cyclohexanones in the course of a natural product synthesis was presented through the desymmetrization of 4-substituted cyclohexanones using Simpkin s base, followed by coupling with diaryliodonium salts [38]. Other binaphthyl iodonium salts related to 21 have also been reported [39]. 

Florini, N., M. Michelazzi, F. Parent , A. Mucci, M. Sola, C. Baratti, V. De Renzi, K. Daasbjerg, S. U. Pedersen, and C. Fontanesi. Electrochemically assisted grafting of asymmetric alkynyl(aryl)iodonium salts on glassy carbon with focus on the alkynyl/ aryl grafting ratio. J. Electroanal. Chem. 710, 2013 41—47. 

The polarization of l" has an impact on the Hirshfeld surface of the iodonium ion (Fig. 9). Iodonium cation is polarized in such a way that the electron-deficient areas are located on both sides of the l" along the S - l" - -S and the electron-rich areas around the S - l" - -S direction. The electron density is expected to be polarized around the halonium ion in such a way that two positive o-holes are formed on the opposite sides of the l". The remaining electron density forms a disk arotmd the halonium center perpendicular to the bonds. The Hirshfeld surface plot is very indicative for the interaction as the red areas depict the interatomic distances shorter than the sum of van der Waals radii (Fig. 9). The complex is slightly more asymmetrical than observed for the asymmetric N- - l" - N complexes, the X" S distances are 2.60 and 2.70 A, and the S- - X" - - -S angles are 171.3° with Rxb = 0.69 and 0.71, respectively. 

When used with diphenyliodonium salts in the presence of a metal and an organocatalyst the enantioselective introduction of a phenyl group at the a-position of aldehydes can be accompUshed [42]. This transformation can be extended to a more general concept of enantioselective a-arylation of aldehydes by deployment of different substituted diaryl-iodonium salts. In these reactions CuBr was used as Lewis acid (Scheme 4.12). Based on these findings the authors were able to develop a rapid asymmetric synthesis of the anti-inflammatory drug (S)-ketoprofen. 

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