Oxidative kinetic resolution of secondary

The complex Pd-(-)-sparteine was also used as catalyst in an important reaction. Two groups have simultaneously and independently reported a closely related aerobic oxidative kinetic resolution of secondary alcohols. The oxidation of secondary alcohols is one of the most common and well-studied reactions in chemistry. Although excellent catalytic enantioselective methods exist for a variety of oxidation processes, such as epoxidation, dihydroxy-lation, and aziridination, there are relatively few catalytic enantioselective examples of alcohol oxidation. The two research teams were interested in the metal-catalyzed aerobic oxidation of alcohols to aldehydes and ketones and became involved in extending the scopes of these oxidations to asymmetric catalysis. 

In 2003, Sigman et al. reported the use of a chiral carbene ligand in conjunction with the chiral base (-)-sparteine in the palladium(II) catalyzed oxidative kinetic resolution of secondary alcohols [26]. The dimeric palladium complexes 51a-b used in this reaction were obtained in two steps from N,N -diaryl chiral imidazolinium salts derived from (S, S) or (R,R) diphenylethane diamine (Scheme 28). The carbenes were generated by deprotonation of the salts with t-BuOK in THF and reacted in situ with dimeric palladium al-lyl chloride. The intermediate NHC - Pd(allyl)Cl complexes 52 are air-stable and were isolated in 92-95% yield after silica gel chromatography. Two diaster corners in a ratio of approximately 2 1 are present in solution (CDCI3). 

Interestingly, the scope of the reaction using this catalyst can be extended to oxidative kinetic resolution of secondary alcohols by using (-)-sparteine as a base (Table 10.2) [25]. The best enantiomeric excess of the alcohol was obtained when a chiral enantiopure base and an achiral catalyst were used. The use of chiral enantiopure catalyst bearing ligand 17 led to low enantioselectivity. 

The groups of Sigman and Stoltz have concurrently published the palladium-catalyzed oxidative kinetic resolution of secondary alcohols using molecular oxygen as the stoichiometric oxidant. Both communications also described a single example of a diol desymmetrization using a palladium catalyst in the presence of (—(-sparteine [Eqs. (10.42) ° and (10.43) ] ... 

Oxidative kinetic resolution of secondary alcohols mediated with a catalytic amount of optically active binaphthyl-type iV-oxyl has been performed with high selectivity". Also, it has mediated oxidative asymmetric desymmetrization of primary alcohols with good selectivity (equation 25)". ... 

Scheme 16 Aerobic oxidative kinetic resolution of secondary alcohols...

Pd(II) catalysts have been widely used for aerobic oxidation of alcohols. The catalytic systems Pd(OAc)2-(CH3)2SO [14] and Pd(OAc)2-pyridine [15] oxidize allylic and benzylic alcohols to the corresponding aldehydes and ketones. Secondary aliphatic alcohols, with relatively high water solubility, have been oxidized to the corresponding ketones by air at high pressure, at 100 °C in water, by using a water-soluble bathophenanthroline disulfonate palladium complex [PhenS Pd(OAc)2] [5d]. The Pd catalyst has also been successfully used for aerobic oxidative kinetic resolution of secondary alcohols, using (-)-sparteine [16]. 

Several other systems have been discovered for the aerobic oxidative kinetic resolution of secondary alcohols. Katsuki has shown that (nitroso)Ru-salen complexes such as 1 can successfully resolve alcohols under photolytic conditions in the presence of dry air (Scheme 4) [9]. A related Ru complex was also able to achieve... 

In 1998 evidence for the existence of a commonly invoked intermediate for a variety of oxygen transfer reactions involving the ]0 = Mn ] moiety was obtained by interception of an ]0 = Mn (salen)(OIPh)] complex (Fig. lA) and a binu-clear [pi-0(Mn (salen)(0IPh))2] complex (Fig. IB) [36]. Later, an ESI-MS study on the Mn-catalyzed oxidative kinetic resolution of secondary alcohols by PhI(OAc)2 reported the observation of a similar manganese salen intermediate [MnV(salen)(PhIO)(OCH(CH3)Ph]+ (Fig. 1C) [6]. This, along with the observation of [Mn "(salen)(PhI(OAc)2)] (Fig. ID), allowed the proposal of a possible catalytic cycle for the kinetic resolution of secondary alcohols by this system. 

The immobilized catalyst provided good enantioselectivity and activity in the heterogeneous catalysis of the oxidative kinetic resolution of secondary alcohols and can be recovered and recycled for four times without obvious loss of enantioselectivity and activity. Oxidative kinetic resolutions of meso-diols, hydroxyl esters, and primary alcohols were also studied using this catalytic system. 

Preceeding this work, palladium/NHC complexes had been used in the aerobic oxidative kinetic resolution of secondary alcohols [93]. The reaction was explored as a measure of match-mismatch interaction between a supporting NHC ligand and an exogenous chiral base. The NHC ligands met two essential criteria compatibility under oxidation conditions and stability toward dis-... 

Palladium catalysts have found application in the oxidative kinetic resolution of secondary alcohols such as 1-phenylethanol. (—)-Sparteine, was used to obtain high levels of enantioselection however, it was found that the nature of the palladium source was critical in obtaining a high chemical selectivity factor Pd2(dba)3 proved superior to Pd(OAc)2 but not as effective as Pd(nbd)Cl2-The observed difference in reactivity, for various palladium catalysts, was attributed to subtle differences in the solubility of the palladium-precatalysts in toluene as well as their ability to complex with (—)-sparteine (eq 32). ... 

A number of other asymmetric enolate protonation reactions have been described using chiral proton sources in the synthesis of a-aryl cyclohexanones. These include the stoichiometric use of chiral diols [68] and a-sulfinyl alcohols [69]. Other catalytic approaches involve the use of a BlNAP-AgF complex with MeOH as the achiral proton source, [70] a chiral sulfonamide/achiral sulfonic acid system [71,72] and a cationic BINAP-Au complex which also was extended to acyclic tertiary a-aryl ketones [73]. Enantioenriched 2-aryl-cyclohexanones have also been accessed by oxidative kinetic resolution of secondary alcohols, kinetic resolution of racemic 2-arylcyclohexanones via an asymmetric Bayer-Villiger oxidation [74] and by arylation with diaryhodonium salts and desymmetrisation with a chiral Li-base [75]. 

Tomizawa M, Shibuya M, Iwabuchi Y (2009) Highly Enantioselective Organocatalytic Oxidative Kinetic Resolution of Secondary Alcohols Using Chirally Modified AZADOs. Org Lett 11 1829... 

More impressive results were observed in two other asymmetric reactions both based on the use of well-known catalysts developed for other transformations that turned out to perform well in new reactions, thanks to the beneficial use of water as solvent. One case is based on the oxidative kinetic resolution of secondary alcohols with chiral Mn(salen) complexes using PhI(OAc)2 as the oxidant (Scheme 23.40). The reaction is poorly enantioselective in dichloromethane (2% ee Krei < 1.1), while in water, in the presence of tetraethylammonium bromide as the phase transfer agent, the reaction is fast (63.4% conversion in 2 h) and highly enantioselective (85.2% ee withKrei 23.7). 3... 

Ferreira, E. and Stoltz, B. (2001). The Palladium-Catalyzed Oxidative Kinetic Resolution of Secondary Alcohols with Molecular Oxygen. J. Am. Chem. Soc., 123, pp. 7725-7726. 

Aerobic Alcohol Oxidations. The combination of PdCl2(CH3CN)2 (5-10 mol%) with (—(-sparteine (20 mol%) constitutes an effective catalyst system for the oxidative kinetic resolution of secondary alcohols with molecular oxygen as the terminal oxidant, with enantiomeric excesses t)q)ically above 90% ee (eq 45). This enantioselective aerobic oxidation has been successfully extended to the desymmetrization of meso-1,3-diols. 

Enantioselective Oxidation of Alcohols. Recently two groups have reported the oxidative kinetic resolution of secondary alcohols using a simple procedure involving a commercially available palladium complex, sparteine, and molecular oxygen (eq The addition of CS2CO3 and f-BuOH provides a... 

Sahoo, S., Kumar, P., Lefebvre, F., and Halligudi, S.B. (2008) A chiral Mn(III) salen complex immobilized onto ionic liquid modified mesoporous silica for oxidative kinetic resolution of secondary alcohols. Tetrahedron Lett, 49, 4865-4868. 

Bera PK, Maity NC, Abdi SHR, Khan N-uH, Km-eshy RI, HC. Macrocychc Mn(III) salen complexes as recyclable catalyst for oxidative kinetic resolution of secondary alcohols. Appl Catal A Gen. 2013 467 542-551. 

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