Quaternary axially chiral

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. 

Piperidines with contiguous quaternary and tertiary stereocenters (for example 248) have been prepared in high enantiomeric purity by intramolecular conjugate addition of enolates generated from a-aminoacid (for example 249 derived from phenylalanine) derivatives (Scheme 74). An axially chiral enolate intermediate was proposed <050BC1609>. 

Quaternary ammonium betaines possessing an anion moiety have emerged as Bronsted base catalysts. The C2-symmetric axially chiral ammonium betaine 177 deprotonates the a-substituted a-nitrocarboxylates (176) to form a structured ion pair that reacts with imines (173) to furnish the corresponding anti-Mannich... 

The resolution of racemic alcohols in which the hydroxyl residue is not at the stereogenic center is of particular interest and can be done through so-called remote resolutions [73]. The best results have been found when the stereocenter is in p-posi-tion with respect to the alcohol fxmction, while when moving the stereocenter to a further position the processes result in a loss of chiral recognition. In this context, Backvall and Deska have reported the KR of axially chiral primary allenic alcohols, which occurred with high enantioselectivities by using a crude preparation of porcine pancreatic lipase (PPL) in combination with five equivalents of vinyl butanoate using DIPE at room temperature (Table 9.2) [74]. In some cases a quaternary stereocenter contains a hydroxymethyl residue, and the remote resolution is achieved... 

Axially Chiral Quaternary Ammonium Salt-Catalyzed Aldol Reactions... 

Inspired by Maruoka s success in using axially chiral C2-symmetric binaphthyl-based N-spiro quaternary ammonium salts, both the Arai [83] and Waser [84] groups developed tartaric acid-derived N-spiro quaternary ammonium salts 51 and 52, respectively. These catalysts could promote the asymmetric alkylation and conjugate addition with good enantioselectivities. 

Interestingly, none of the stereoselective reactions described previously assembles a new chiral center instead, the applied strategies rely on previously existing, special chiral characteristics of the substrates (prochiral moieties or fluxional axial chirahty). In contrast to these approaches, a recently published report relies solely on catalyst design to generate a new stereocenter in the product through chelate-assisted hydroarylation (Scheme 23.54) [166]. The most selective Rh catalyst 31 uses a biaryl-substituted Cp ring as the structural element to induce enantioselectivity. After the reaction, the hydroarylation product with a new quaternary stereocenter can be isolated in 87% yield and 91% ee. 

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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