Diastereoselectivity double

Double lithiation of bisoxazoline 314 is possible with either s-BuLi or f-BuLi, and each base gives different planar diastereoselectivity. Double lithiation with i-BuLi, quenching the dianion with ClPPh2, leads to the C2-symmetric bisphosphine 315 as the... 

Scheme 6.59 Typical 4-nitrocyclohexanone derivatives prepared from the thiourea 12/TMC-catalyzed enantio- and diastereoselective double Michael addition of y,5-unsaturated P-ketoesters to frans-P-nitrostyrene.

The spirodiepoxide 1 is an intriguing new approach to relative and absolute stereocontrol. It will be interesting to see what other nucleophiles can be used in the opening. It is possible that a chiral oxygen transfer reagent, such as the dioxirane prepared by the Shi protocol, would convert 12 to 1 with improved diastereoselectivity (double diastereoselection). 

Merck has used a diastereoselective double RCM in the synthesis of NK-1 receptor antagonists (Scheme 28.3).33 Previously reported studies by the same group showed that amino acid-derived tetraene 12 smoothly underwent ring closure in a diastereoselective fashion to give the corresponding spirocyclic compounds 13 in excellent diastereoselectivity.34 An extension of this work to the tetraene system derived from phenylglycine gave the desired spirocycle in 86% yield and 70% ds. 

Scheme 1.6. Regio- and diastereoselective double Diels-Alder addition to Cgo using a threitol derivative as imprinting template.

Alternatively, an achiral amine can be used as the palladium ligand and an optically active secondary amine can be added successively (auxiliary-induced stereoselectivity). The third possibility, which afforded the highest enantiomeric excess on ( )-2-butene, is to use the optically active amine both as ligand and nucleophile, hence combining reagent- and auxiliary-induced diastereoselectivity (double asymmetric induction). 

The earliest general method for the reductive deoxygenation of oxiranes to alkenes involved multistep procedures in which halohydrins were intermediates. Comforth, for example, used an oxirane deoxygenation in an early synthesis of squalene (Scheme 11). Diastereoselective double addition of ho-mogeranyllithium (23) to the dichloro diketone (24) gave the bis(chlorohydrin) (25), which was first converted to the diepoxide (26). Subsequent treatment with Nal and Zn in HOAc buffered with NaOAc gave squalene (27). 

Keywords Stereogenic reactions. Mechanism control. Substrate and reagent control. Stereoselectivity, Simple diastereoselectivity, exo-endo-Diastereoselectivity, Double stereodifferentiation, Chiral catalysts, Chiraphor and catalaphor. Hybrid catalysts. Chiral auxiliary... 

Burke and Jiang reported that the palladium-catalyzed diastereoselective double allylation of the diol bis(allylic acetate) 613 using (R,R) DPPBA 607 afforded the bis-tetrahydrofuran core 614 in 97% yield (Scheme 187).265 The resulting diene 614 was further transformed into a known intermediate 615 for the synthesis of uvaricin. They demonstrated that palladium (0)-catalyzed desymmetrization of the C2 diol 616 with Trost s ligand 607 afforded the tetrahy-drofuran 617 diastereoselectively (Scheme 188).266 The product 617 was manipulated to the F ring of halichondrin B (618). 

The first examples of highly diastereoselective double asymmetric reactions involving chiral allyl metal reagents were obtained in reactions with D-glyceraldehyde acetonide (151 Table 6). Aldehyde (151) displays an 80 20 preference for (154) in reactions with the achiral pinacol allylboronate (144 entry 4),25.ioi selectivity for (154) improves to 96-98% with reagents (-)-(215) and (RJi)-... 

The unusual chiral (3-methoxy-y-amino acid dolaproine (Dap) is the most complex unit of dolastatin 52, which has a remarkable antineoplastic activity and is now in Phase II human cancer clinical trials. Many synthetic strategies such as aldol condensation and a cobalt-catalyzed Reformatsky reaction have been employed in its synthesis. Almeida and Coelho have demonstrated a stereoselective synthetic method for A-Boc-dolaproine (53) through a sequence of MBH reaction, a diastereoselective double bond hydrogenation and hydrolysis of the ester functional group (Scheme 5.8). ... 

The practical and convenient solvent-free iridium-catalyzed [2 + 2 + 2] cycloaddition of a,(D-diynes and alkynes was explored as an efficient route for the synthesis of isoindolines, dihydrobenzo[c]frirans, and indanes (13S2003).The asymmetric synthesis of C2-symmetric axially chiral biaryls was achieved by the cationic rhodium(I)/l,3-bis(diphenylphosphino)pro-pane (dppp)-catalyzed diastereoselective double [2 + 2 + 2] cycloaddition of (R)-3-butyn-2-ol-derived tetraynes with functionalized monoynes (13EJOC6774). 

This DTDA sequence begins with a completely diastereoselective double DA reaction between [3]dendralene 27 and / -benzoquinone, yielding tetracycle 29 (Scheme 12.4) [5].This compound was not isolated, and the subsequent addition of cyclopentadiene to the same reaction vessel allowed for two more DA reactions, generating the octacyclic skeleton 30 as a mixture of diastereomers. 

The asymmetric synthesis of a symmetric [1 l]helicene-like molecule was accomplished by the cobalt-mediated diastereoselective double intramolecular [2 + 2 + 2] cycloaddition of a symmetric chiral hexayne possessing two stereogenic centers (Scheme 10.16) [8], Like the asymmetric synthesis of the [7]helicene-like molecules shown in Scheme 10.13, (5) centrochirality induced predominantly P) helical chirality in the reaction of the bulky p-tolyl-substituted hexayne. 

Michaud et al. (1997) reported that nitromethane reacts via a diastereoselective double Michael addition with electrophilic alkenes in the presence of piperidine under solvent-free condition and focused microwave irradiation. It afforded functionalized cyclohexenes and there was no formation of cyclopropane. 

Evans has disclosed the diastereoselective double epoxidation of 12-mem-bered ring 1,5-diene lactone 50 for the preparation of a key fragment en route to the polyether antibiotic lonomycin A (Equation 6) [21], The inherent facial biases imposed by the macrocycle led to the preferential formation of 51 in 9 1 dr. 

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