Backvall system

This system was also shown to catalyze the DKR of 1-phenylethanol [13], interestingly in the presence of the stable free radical TEMPO as cocatalyst (Fig. 9.12). The exact role of the TEMPO in this system has yet to be elucidated and the reaction conditions need to be optimized, e.g. by preforming the active catalyst as in the Backvall system described above. 

Hult and co workers have reported a modification to the Backvall system in which 1 equiv of isopropyl 2 methoxyacetate was used as the acyl donor in combination with... 

The modified Backvall system was three times faster than the original system and gave similar yields and enantioselectivity for a series of amine and diamine substrates. Attempts to polymerize a chiral diamine with a diacyl donor using... 

Figure 11.4 Modified Backvall system for the DKR of amine substrates.

The nucleophilic attack of the water or hydroxide species takes place in an anti fashion i.e. the oxygen attacks from outside the palladium complex and the reaction is not an insertion of ethene into the palladium oxygen bond. This has been demonstrated in a model reaction by Backvall [4], The reaction studied was the Wacker reaction of dideuterio-ethene (cis and trans) in the presence of excess of LiCl, which is needed to form 2-chloroethanol as the product instead of ethanal. The latter product would not reveal the stereochemistry of the attack Note that all of the mechanistic work has been carried out, necessarily, on systems deviating in one aspect or another from the real catalytic one. The outcome depends strongly on the concentration of chloride ions [5],... 

Subsequently, Backvall and coworkers developed triple-catalysis systems to enable the use of dioxygen as the stoichiometric oxidant (Scheme 3) [30-32]. Macrocyclic metal complexes (Chart 1) serve as cocatalysts to mediate the dioxygen-coupled oxidation of hydroquinone. Polyoxometallates have also been used as cocatalysts [33]. The researchers propose that the cocatalyst/BQ systems are effective because certain thermodynamically favored redox reactions between reagents in solution (including the reaction of Pd° with O2) possess high kinetic barriers, and the cocatalytic mixture exhibits highly selective kinetic control for the redox couples shown in Scheme 3 [27]. 

Ruthenium compounds are widely used as catalysts for hydrogen-transfer reactions. These systems can be readily adapted to the aerobic oxidation of alcohols by employing dioxygen, in combination with a hydrogen acceptor as a cocatalyst, in a multistep process. For example, Backvall and coworkers [85] used low-valent ruthenium complexes in combination with a benzoquinone and a cobalt Schiff s base complex. The proposed mechanism is shown in Fig. 14. A low-valent ruthenium complex reacts with the alcohol to afford the aldehyde or ketone product and a ruthenium dihydride. The latter undergoes hydrogen transfer to the benzoquinone to give hydroquinone with concomitant... 

However, since the catalytic system is homogenous, carefully adjusted reaction conditions were needed to circumvent the second nonselective catalytic cycle. Slow addition of the alkene and the hydrogen peroxide was necessary to obtain good enantioselectivities (Table 6) [13]. Recently, Backvall s group reported that the Cinchona alkaloid ligand participated in the reoxidation process and took the role of NMO in the catalytic cycle [15]. Versions of the triple catalytic system with vanadyl acetylacetonate replacing the flavin analogue [16] or m-CPBA as the terminal oxidant [17] have been developed and successfully applied to racemic dihydroxylation reactions. 

In the group of Backvall a method was developed involving palladium and benzoquinone as cocatalyst (Fig. 4.42) [103]. The difficulty of the catalytic reaction lies in the problematic reoxidation of Pd(0) which cannot be achieved by dioxygen directly (see also Wacker process). To overcome this a number of electron mediators have been developed, such as benzoquinone in combination with metal macrocycles, heteropolyacids or other metal salts (see Fig. 4.42). Alternatively a bimetallic palladium(II) air oxidation system, involving bridging phosphines, can be used which does not require additional mediators [115]. This approach would also allow the development of asymmetric Pd-catalyzed allylic oxidation. 

Following on from this initial publication of Backvall, many groups have reported on a variety of ruthenium-based systems for the DKR of secondary alcohols [9-17] mainly with the goal of eliminating the need for added base and ketone and reducing the reaction time by increasing the rate of racemization. Some examples of ruthenium complexes (1-8) which have been used as the racemization catalysts in these systems are depicted in Fig. 9.5. 

Several groups have reported [9] ruthenium-based systems that are compatible with the enzyme and acyl donor. The most active of these is the one based on catalyst 4 developed by Backvall [17, 18] which effects the DKR of secondary al-... 

Backvall and co-workers have demonstrated that m-annulated furans are obtained in excellent yields from 7-hydroxy alkenes by Pd(ll)-catalyzed oxidative heteroatom cyclization (Equation 83) <1995TL7749>. The scope of the Pd(ll) catalyst system with O2 in DMSO as reoxidant has been demonstrated with ring sizes five to seven (n = 1-3). 

Ligand systems with pyrimidines have, in effect, internal arm-off donors that present less of a problem of potentially increasing the rate of Pd-N bond rupture via a second-order process from the proximate donor. Gogoll and Backvall showed that 2-2 -bipyrimidyl (bpm) (64) was useful in this regard. Hence interconversion of the H-4 and H-6 is indicative of Pd-N bond rupture. ... 

Recently, 3,5-bis(trifluoromethyl)benzeneseleninic acid has been used in a tandem catalytic epoxidation." The concept of tandem catalysis has been applied to oxidation reactions by Backvall and co-workers for the direct dihydroxylation of olefins using a couple catalytic system and hydrogen peroxide as the terminal oxidant." In this context, the seleninic acid was used in combination with a trifluoromethyl oxaziridine catalyst (Scheme 17), using urea hydrogen peroxide as the terminal oxidant." This system showed... 

Pd(II)-mediated cascade cyclizations have also been employed for the construction of other types of heterocyclic systems. For example, Backvall reported that the oxidative cyclization of dienyl amides occurred to give pyrrolizidines and indolizi-dines. Thus, treatment of 629a,b with Pd(OAc)2 and CuCl2/02 provided 630a,b in 90 and 85% yield, respectively (Scheme 104) (92JA8696). 

The triple catalytic systems introduced by Backvall et ai. [141-144] (cf. Section 3.2.1.), producing ketones from olefins, lead in some cases (cyclic olefins) to allylic oxidation products... 

This can be regarded as a double catalytic system, reminiscent of the ones described by Backvall et ai. [33]. 

For the achiral Ru(Cl)2(PPhj)j system, Backvall and co-workers have concluded that the active catalyst is the dihydride, Ru(PPh)3(H>2. The latter is formed from Ru(Cl)2(PPh3)3 in isopropanol with added base and was identified by P NMR. The dihydride gave immediate reaction between cyclopentanol and acetone in the presence of K2CO3, while Ru(CI)2(PPh3)3 and Ru(H)(Cl)(PHi3)3 were slower to react and show induction periods. 

However, if the H and D in the dihydride are chemically equivalent or become scrambled, then the racemate will have 50% of the D on the a-carbon. In practice, the deuterium content of the product is always somewhat less than predicted. For the Ru(PPh>3(H)2 catalyst described in the previous paragraph, 37% of the expected D was found on the a-carbon. Pkmies and Backvall applied this method to a number of catalysts and found that many Rh and Ir catalysts gave >90% retention of D on the a-carbon, suggesting a monohydride pathway. The same was true for most of the Ru systems tested, except for the case mentioned above and for (Ph3p)2Ru(Cl)2(Ti2-NH2CH2CH2l ). 

Ronn, Backvall, and Anderssont i have applied the catalyst system to the cyclization of cycloalkenyl alcohols leading to bicycUc ethers (Scheme 15). In this cyclization, the use of Cu(OAc)2 and NaOAc as cocatalysts retards the rate of reaction. 

---