Backvall reaction

An interestmg Diels-Alder reaction using chiral enammes is reported by Backvall, m which a cychc nitronate is formed m good yield and excellent diastereoselecnvity fEq 8 98 ... 

Racemization of amines is difficult to achieve and usually requires harsh reaction conditions. Reetz et al. developed the first example of DKR of amines using palladium on carbon for the racemization and CALB for the enzymatic resolution [35]. This combination required long reaction times (8 days) to obtain 64% yield in the DKR of 1-phenylethylamine. More recently, Backvall et al. synthesized a novel Shvo-type ruthenium complex (S) that in combination with CALB made it possible to perform DKR of a variety of primary amines with excellent yields and enantioselectivities (Figure 4.13) [36]. 

In a different context, Backvall et al. have reported another type of substitution, the arenethiolatocopper(I)-catalysed substitution reaction of... 

More recently, Backvall et al. have reported the use of arenethiolatocopper(I) as a catalyst for the analogous substitution reaction of Grignard reagents with allylic substrates. In this case, the crosscoupling reaction could occur in an a(SN2) or y(Sn2 ) manner, depending on the reaction conditions. In all cases, the y-product was isolated as the sole product with moderate to quantitative... 

An interesting Diels-Alder reaction using chiral enamines is reported by Backvall, in which a cyclic nitronate is formed in good yield and excellent diastereoselectivity (Eq. 8.98).155... 

The principle of hydrogen transfer reactions has been applied to a variety of oxidative transformations of alcohols with Ru11 catalysts.72 Among them, one interesting application is the aerobic oxidation of alcohols developed by Backvall,153-157 which can be performed with a catalytic... 

Backvall and Juntunen and Fuchs and Braish have developed ( )-2-phenylsuphonyl-1,3-dienes prepared under Julia conditions as versatile synthones for a variety of organic transformations103. These dienes undergo facile Diels-Alder reaction and subsequent 1,4-elimination of sulphinic acid by base to generate a new diene (equation 62)103a. An elegant extension of this method is to use chiral sulfinylmaleate which, on Diels-Alder... 

J. E. Backvall, Nucleophilic Attack on Coordinated Alkenes , in Reaction of Coordinated Ligands (Ed. P. S. Braterman), Plenum Press, London 1986, pp. 679-731. 

Studies aimed at the elucidation of reaction mechanisms have been performed by many groups, notably by those of Backvall [28]. In test reactions, typically enantiopure 1-phenylethanol labeled with deuterium at the 1-position (8) is used. The compound is racemized with acetophenone (9) under the influence of the catalyst and after complete racemization of the alcohol, the deuterium content of the racemic alcohol is determined. If deuterium transfer proceeds from the a-carbon atom of the donor to the carbonyl carbon atom of the acceptor the deuterium is retained, but if it is transferred to the oxygen atom of the acceptor it is lost due to subsequent exchange with alcohols in the reaction mixture (Scheme 20.4). 

The mechanism of the Meerwein-Pondorf-Verley reaction is by coordination of a Lewis acid to isopropanol and the substrate ketone, followed by intermolecular hydride transfer, by beta elimination [41]. Initially, the mechanism of catalytic asymmetric transfer hydrogenation was thought to follow a similar course. Indeed, Backvall et al. have proposed this with the Shvo catalyst [42], though Casey et al. found evidence for a non-metal-activation of the carbonyl (i.e., concerted proton and hydride transfer [43]). This follows a similar mechanism to that proposed by Noyori [44] and Andersson [45], for the ruthenium arene-based catalysts. By the use of deuterium-labeling studies, Backvall has shown that different catalysts seem to be involved in different reaction mechanisms [46]. 

In 1997, Backvall and Jonasson published a procedure for the 1,2-oxidation of terminal allenes 7 [5]. In this case the reaction conditions were chosen so that the (vinyl)palladium complex equilibrates back to the allene complex. Using bromide instead of chloride as a nucleophile, the 2-bromo-jt-allyl complex 9 is the major intermediate present in the reaction mixture. A catalytic reaction was developed with the use of 5 mol% palladium acetate and p-benzoquinone (BQ) as terminal oxidant (Scheme 17.5). 

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],... 

Pellissier, H., Recent developments in dynamic kinetic resolution. Tetrahedron, 2008, 64, 1563-1601 Turner, N.J., Enzyme catalysed deracemisation and dynamic kinetic resolution reactions. Curr. Opin. Chem. Biol., 2004, 8, 114-119 Gmber, C.C., Lavandera, I., Faber, K. and Kroutil, W., From a racemate to a single enantiomer deracemisation by stereoinversion. Adv. Synth. Catal., 2006, 348, 1789-1805 Pellissier, H., Dynamic kinetic resolution. Tetrahedron, 2003, 59, 8291-8327 Pmnies, O. and Backvall, J.-E., Combination of enzymes and metal catalysts. A powerful approach in asymmetric catalysis. Chem. Rev., 2003, 103, 3247-3261. 

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]. 

The intramolecular addition of carbon nucleophiles to alkenes has received comparatively little attention relative to heterocyclization reactions. The first examples of Pd-catalyzed oxidative carbocyclization reactions were described by Backvall and coworkers [164-166]. Conjugaled dienes with appended al-lyl silane and stabilized carbanion nucleophiles undergo 1,4-carbochlorination (Eq. 36) and carboacetoxylation (Eq. 37), respectively. The former reaction employs BQ as the stoichiometric oxidant, whereas the latter uses O2. The authors do not describe efforts to use molecular oxygen in the reaction with allyl silanes however, BQ was cited as being imsuccessful in the reaction with stabihzed car-banions. Benzoquinone is known to activate Ti-allyl-Pd intermediates toward nucleophilic attack (see below. Sect. 4.4). In the absence of BQ, -hydride eUm-ination occurs to form diene 43 in competition with attack of acetate on the intermediate jr-allyl-Pd" species to form the 1,4-addition product 44. 

Backvall J-E (2004) In de Meijere A, Diederich F (eds) Metal-catalyzed crosscoupling reactions, vol 2. Wiley, Chichester, p 479... 

Compared to the enantioselective allylic alkylation using soft nucleophiles, the reaction with Grignard reagents has received much less attention. The first enantioselective copper-catalyzed allylic alkylation with alkylmagnesium reagents was reported in 1995 by the groups of Backvall, van Koten and coworkers (Scheme 13). ... 

In order to distinguish between the dihydridic and the monohydridic routes in hydrogen-transfer reactions, Backvall and coworkers developed an optically active a-deuterated alcohol. If the dihydridic route was occurring the deuterium would be scrambled between carbon and oxygen atoms whereas if the monohydridic... 

Reactions of the HNiL3CN complex with 1,3-cyclopentadiene, 1,3-cyclo-hexadiene, and 1,3-cyclooctadiene gave intermediates with decreasing stabilities in that order the 1,3-cyclooctadiene intermediate was not spectroscopically observable. The cyclohexadiene adduct was shown to be the cyclohexadienyl complex 12 by its proton spectra, with resonances of H , Hb, and —(CH2)3— at 14.53, 6.06, and 8.47, respectively these values are close to the chemical shifts found earlier (51) for 13 14.52,5.86, and 8.48. The reaction of DNi[P(OMe)3]X with cyclopentadiene gives 13-d, with addition of D and Ni to the same side of the ring (52). Backvall and Andell (55) have shown, using Ni[P(OPh)3]4 and deuterium cyanide (DCN), that addition of D and CN to cyclohexadiene is stereospecifically cis, as expected for jt-allyl intermediate 12. 

F. F. Huerta and J. E. Backvall, Enantio-selective synthesis of beta-hydroxy acid derivatives via a one-pot aldol reaction -dynamic kinetic resolution, Org. Lett. 2001, 3(8), 1209-1212. 

Backvall et al. utilized a stereoconvergent palladium-catalyzed SN2 reaction of a-allenic acetates 39 for the synthesis of (Z, )-2-bromo-l,3-dienes 40 [29]. 

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... 

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