Asymmetric reactions deprotonation

Only three PBP complexes of Fe(III) with acyclic ligands from the class of bis(acylhydrazone) of dap have been structurally characterized at present (41,49,53) and this prompted studies in that direction. Both direct and template synthesis afforded the complex [Fe(Hdapsox) Cl2] - 1/2H20 (9) with a monoanionic H2dapsox ligand (7). Protonation of the coordinated ligand was unsuccessful even upon addition of HC1 to the reaction mixture (Scheme 5). In spite of asymmetrical mono-deprotonation, the ligand was symmetrically pentadentately... 

Ephedrine becomes a chiral ligand of metal atoms by the deprotonation of the hydroxy group and by the presence of the nitrogen atom. - Highly enantioselective asymmetric reactions are known using chiral ephedrine-type ligands. 

When there is a heteroatom as a second substituent on the anionic carbon bearing nitrogen, asymmetric reactions provide an enantioenriched formyl anion synthetic equivalent. Gawley has used the chiral auxiliary approach in a deprotonation-substitution sequence to make highly diastereoenriched 13 and 14, and converted the separated diastereoisomers to the enantiomeric diols 18 and 19 (Scheme 5). A number of cases are reported. Structural, kinetic and computational studies were carried out and found to be consistent with reaction via a complex species [13]. 

Asymmetric reaction of the sulfides bearing a tricarbonyl(ri -arene)chromi-um complex was shown to be successful by Gibson and Simpkins [48,49]. The benzyhc methylene groups in tricarbonyl(ri -phenylmethyl alkyl sulfide)chro-mium(O) and tricarbonyl(ri -l,3-dihydroisobenzothiophene)chromium(0) were highly asymmetrically functionahzed by deprotonation with a chiral bis-Uthium amide and subsequent electrophihc reactions (Tables 4 and 5). 

Chiral Nitrogen Donor Ligands (Amines and Oxazolines). 1,2-Diphenyl-ethylenediamine (DPEN (56)) and its alkylated and tosylated derivatives, as well as 1,2-cyclohexane-diamine (CHDA (57)) based ligands proved to be applicable in a range of asymmetric reactions (Fig. 7), especially in enantioselective transfer hydrogenations providing ees more than 90% for acetophenone as substrate. Crucial steps of this reaction are the irreversible deprotonation of the ligand... 

The potential of metal carbenes in stereoselective synthesis is based on both the pronounced acidity of the a-CH in the alkyl side chain - which may be exploited in aldol and Michael-type reactions - and on cycloaddition reactions centered either on the metal or the carbene ligand. The incorporation of a carbohydrate backbone into the carbene ligand generally allows for an asymmetric modification of these carbon-carbon bond-forming reactions. Deprotonation of 2-oxacyclopen-tylidene complexes 76a/b and 270-279 generates the conjugate bases that can be... 

Asymmetric induction by sulfoxide is a very attractive feature. Enantiomerically pure cyclic a-sulfonimidoyl carbanions have been prepared (98S919) through base-catalyzed cyclization of the corresponding tosyloxyalkylsulfoximine 87 to 88 followed by deprotonation with BuLi. The alkylation with Mel or BuBr affords the diastereomerically pure sulfoximine 89, showing that the attack of the electrophile at the anionic C-atom occurs, preferentially, from the side of the sulfoximine O-atom independently from the substituent at Ca-carbon. The reaction of cuprates 90 with cyclic a,p-unsaturated ketones 91 was studied but very low asymmetric induction was observed in 92. 

An excellent synthetic method for asymmetric C—C-bond formation which gives consistently high enantioselectivity has been developed using azaenolates based on chiral hydrazones. (S)-or (/ )-2-(methoxymethyl)-1 -pyrrolidinamine (SAMP or RAMP) are chiral hydrazines, easily prepared from proline, which on reaction with various aldehydes and ketones yield optically active hydrazones. After the asymmetric 1,4-addition to a Michael acceptor, the chiral auxiliary is removed by ozonolysis to restore the ketone or aldehyde functionality. The enolates are normally prepared by deprotonation with lithium diisopropylamide. 

Herrmann et al. reported for the first time in 1996 the use of chiral NHC complexes in asymmetric hydrosilylation [12]. An achiral version of this reaction with diaminocarbene rhodium complexes was previously reported by Lappert et al. in 1984 [40]. The Rh(I) complexes 53a-b were obtained in 71-79% yield by reaction of the free chiral carbene with 0.5 equiv of [Rh(cod)Cl]2 in THF (Scheme 30). The carbene was not isolated but generated in solution by deprotonation of the corresponding imidazolium salt by sodium hydride in liquid ammonia and THF at - 33 °C. The rhodium complexes 53 are stable in air both as a solid and in solution, and their thermal stability is also remarkable. The hydrosilylation of acetophenone in the presence of 1% mol of catalyst 53b gave almost quantitative conversions and optical inductions up to 32%. These complexes are active in hydrosilylation without an induction period even at low temperatures (- 34 °C). The optical induction is clearly temperature-dependent it decreases at higher temperatures. No significant solvent dependence could be observed. In spite of moderate ee values, this first report on asymmetric hydrosilylation demonstrated the advantage of such rhodium carbene complexes in terms of stability. No dissociation of the ligand was observed in the course of the reaction. 

Even if organocatalysis is a common activation process in biological transformations, this concept has only recently been developed for chemical applications. During the last decade, achiral ureas and thioureas have been used in allylation reactions [146], the Bayhs-Hillman reaction [147] and the Claisen rearrangement [148]. Chiral organocatalysis can be achieved with optically active ureas and thioureas for asymmetric C - C bond-forming reactions such as the Strecker reaction (Sect. 5.1), Mannich reactions (Sect. 5.2), phosphorylation reactions (Sect. 5.3), Michael reactions (Sect. 5.4) and Diels-Alder cyclisations (Sect. 5.6). Finally, deprotonated chiral thioureas were used as chiral bases (Sect. 5.7). 

Addition of such a-lithiosulfinyl carbanions to aldehydes could proceed with asymmetric induction at the newly formed carbinol functionality. One study of this process, including variation of solvent, reaction temperature, base used for deprotonation, structure of aldehyde, and various metal salts additives (e.g., MgBrj, AlMej, ZnClj, Cul), has shown only about 20-25% asymmetric induction (equation 22) . Another study, however, has been much more successful Solladie and Moine obtain the highly diastereocontrolled aldol-type condensation as shown in equation 23, in which dias-tereomer 24 is the only observed product, isolated in 75% yield This intermediate is then transformed stereospecifically via a sulfoxide-assisted intramolecular 8, 2 process into formylchromene 25, which is a valuable chiron precursor to enantiomerically pure a-Tocopherol (Vitamin E, 26). 

Several stress tests were performed before scale-up. If the asymmetric deprotonation of 19 was carried out at -55 to -45 °C instead of-70 to -60 °C, product 5 from the coupling reaction was obtained in a significantly lower 85% ee although the yield was not affected (83%). An overcharge of (-)-sparteine provided only a marginal improvement in the ee of product 5 for example, l.lequiv of sparteine provided a 93% ee while 0.90 equiv of sparteine gave a slightly eroded 89% ee. 

Alonso et al. (2005) described anion-radical proton abstraction from prochiral organic acids. If the anion radicals were formed from homochiral predecessors, asymmetric deprotonation can be reached. However, low reactivity of the anion radical is required Slow proton transfer, that is, high activation energy of the reaction discriminates well between diastereoselective transition states. 

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