Allene derivatives asymmetric reactions

All of the reactions discussed above are cyclic carbometallation reactions of metallacycles. Very recently, an interesting Cr-catalyzed carboalumination of propargyl derivatives producing allenes via a carbometallation-elimina-tion sequence has been studied. This reaction provides an asymmetric synthesis of chiral allenes (Scheme 57). 

The asymmetric synthesis of allenes via enantioselective hydrogenation of ketones with ruthenium(II) catalyst was reported by Malacria and co-workers (Scheme 4.11) [15, 16]. The ketone 46 was hydrogenated in the presence of iPrOH, KOH and 5 mol% of a chiral ruthenium catalyst, prepared from [(p-cymene) RuC12]2 and (S,S)-TsDPEN (2 equiv./Ru), to afford 47 in 75% yield with 95% ee. The alcohol 47 was converted into the corresponding chiral allene 48 (>95% ee) by the reaction of the corresponding mesylate with MeCu(CN)MgBr. A phosphine oxide derivative of the allenediyne 48 was proved to be a substrate for a cobalt-mediated [2 + 2+ 2] cycloaddition. 

Palladium/silver-catalyzed Heck reactions have usually involved vinyl or aryl halides and alkenes, but these reaction conditions were also extended to allenes. Indeed, Zenner and Larock65 showed that simple alkyl allenes readily reacted with aryl and vinyl iodide derivatives in the presence of palladium acetate or chloride and silver phosphate. Moreover, the reaction could be rendered asymmetric using chiral ligands the best one was a bisoxazolidine derivative (Scheme 10.37). 

Indium-promoted reaction of l,4-dibromo-2-butyne with carbonyl compounds gives 1,3-butadiene derivatives via the allenic indium intermediates (Scheme 56).220 Similar indium-mediated l,3-butadien-2-ylation reactions of optically pure azetidine-2,3-diones have been investigated in aqueous media, offering a convenient asymmetric entry to the 3-substituted 3-hydroxy-/ -lactam moiety (Equation (40)). The diastereoselectivity of the addition reaction is controlled by the bulky chiral auxiliary at Q4 221 222... 

A synthesis of the Inhoffen-Lythgoe diol (46.7, Scheme 2.46), a useful intermediate in the synthesis of Vitamin D derivatives, demonstrates the use of a chiral acetal in an asymmetric tandem cyclisation reaction.102 Once again, Lewis acid co-ordination to the less hindered oxygen of the acetal 46.1 initiated a Prins-like cyclisation that terminated by attack of the propargylsilane on an incipient tertiary carbocation. After removal of the chiral auxiliary, the allene function in the alcohol 46.4 was transformed into the side chain of 46.7 with the creation of two new stereogenic centres. 

Asymmetric and enantioselective olefination reactions continue to be of interest. Wadsworth-Emmons reactions of 4-substituted cyclohexanones with the phosphonate (147), which carries a chiral benzopyrano-isoxazolidine substituent, proceed with diastereomeric excesses of 80-90% and hence provide another example of such an approach to enantiomerically pure, axially dissymmetric cyclohexylidene derivatives. A further example of trapping of in situ generated ketenes by Wadsworth-Emmons reactions to give allene carboxylates has been reported and the reaction has been extended to enantioselective synthesis by use of the optically active phosphonates (148) (Scheme 14). Moderate to good chemical yields and e.e. values up to 84% were obtained depending on the nature of (148) and the reactions conditions. 

Efficient asymmetric carbopalladation occurred in the reaction of the racemic allene 441 with iodobenzene and malonate using BPPFOAc (Xl-14) as a chiral ligand. The chiral malonate derivative 442 with 95 % ee was obtained in 77 % yield [167],... 

In 2008, Willis and co-workers developed a highly enantioselective inter-molecular hydroacylation reaction employing ortfto-S-substituted benzal-dehydes 51 and 1,3-disubstituted allenes 52 (Scheme 8.25). When using a (7 ,/ )-Me-DuPhos-derived cationie rhodium catalyst, excellent yields and ee were obtained. Extension of the substrate scope to a trisubstituted allene led to the product with high ee, but in a disappointingly low yield. It was revealed that the reaction was not a simple kinetic resolution of the racemic allene but rather proceeded by dynamie kinetie asymmetric transformation. 

The nickel-iminophosphine-catalysed 4- -2-cycloaddition of enones with allenes formed highly substituted dihydropyrans. The enantioselective amine-catalysed 4-I-2-cycloaddition of allenoates with oxo-dienes produced polysubstituted dihydropyrans in high yields and with high enantioselectivities. Novel enam-ine/metal Lewis acid bifunctional catalysis has been used in the asymmetric inverse-electron-demand hetero-Diels—Alder reactions of cyclic ketones with Q ,j9-unsaturated a-ketoesters. The 4- -2-cycloaddition of acylketenes (80) with 2-unsubstituted and 2-monosubstituted 3-aryl-2//-azirines (81) produced 1 1 (82) or 2 1 (83) adducts, being derivatives of 5-oxa-l-azabicyclo[4.1.0]hept-3-ene or 5,7-dioxa-l-azabicyclo[4.4.1]undeca-3,8-diene. The formation of the monoadducts proceeds via a stepwise non-pericyclic mechanism (Scheme 25). A-heterocyclic carbene-catalysed 4- -2-cycloaddition of ketenes with 1-azadienes yielded optically active 3,4-dihydropyrimidin-2-ones (93% ee) ... 

Ma has developed a three-component allene carboamination reaction for the stereoselective synthesis of 2,5-as-disubstituted pyrrolidine derivatives [54]. A representative transformation involving allene 58, 4-iodoanisole, and imine 59 that generates 60 in 90% yield is shown below (Eq. (1.28)). The reaction is believed to proceed through the intermediate Jt-allylpalladium complex 62, which is formed by carbopalladation of the alkene to give 61 followed by addition of the malonate anion to the activated imine. Intramolecular capture of the allylpalladium moiety by the pendant nitrogen nucleophile affords the pyrrolidine product. A related asymmetric synthesis of pyrazolidines that employs azodicarboxylates as one of the electrophilic components has also been reported [55]. The pyrazolidine products are obtained with up to 84% ee when chiral bis oxazolines are employed as ligands. 

Transition metal-catalysed methods for carbenoid insertion into C-H bonds remain well documented. The asymmetric intramolecular Cu(II)-catalysed C-H insertion reactions of (i) a-diazo-/ -keto esters and phosphonates and (ii) a-diazo sulfones have been described. One can note that the optimal reaction conditions have been found to be quite similar regardless of the nature of the carbenoid precursor the best conditions featured CUCI2 as Cu(II)-source, bis(oxazoline) (68) as chiral ligand and sodium tetrakis[3,5-bis(trifluoromethyl)phenyl] borate (i.e., NaBARF) as additive. Under the so-optimized reaction conditions, each of these carbenoid sources have been eonverted into five-membered cyclopentanone-based derivatives (69), whereas a-sulfonyl diazo esters (70) have led to six-membered cyclic compounds (71), thus featuring a distinct but well-known selectivity. In a related work, the asymmetric C-H insertion cyclization of (70) to (71) has also been achieved under Rh(II)-catalysis, using a combination of Rh2(5-pttl)4 (72) as chiral catalyst and menthyl ester as chiral auxiliary. As already mentioned in the previous section, allene-containing substrates (49) have been shown to undergo an intramolecular C-H insertion process under Rh(II)-catalysis. ... 

For asymmetric synthesis, we had to prepare the enantiomerically pure allene 55 with the proper relative stereochemistry. The allene moiety could be synthesized from epoxy propargyhc derivative 56 through SN2 -type reaction with a Grignard reagent. The epoxy propargylic substrate would be synthesized from allylic alcohol 57 via Sharpless epoxidation for introducing the appropriate stereochemistry of the protected allenyl alcohol. For the stereoselective synthesis of 56, the allylic alcohol 57 would be prepared enantioselectively (Scheme 16). 

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