Oxidative difunctionalization

Several types of Pd-catalyzed or -promoted reactions of conjugated dienes via TT-allylpalladium complexes are known. The Pd(II)-promoted oxidative difunctionalization reactions of conjugated dienes with various nucleophiles is treated in Chapter 3, Section 4, and Pd(0)-catalyzed addition reactions of conjugated dienes to aryl and alkenyl halides in this chapter. Section 1.1.1. Other Pd(0)-catalyzed reactions of conjugated dienes are treated in this section. 

Reaction of conjugated dienes with aryl and alkenyl halides is treated in Section 3.2 and oxidative difunctionalization of conjugated dienes with Pd(II) is treated in Section 11.3. This chapter covers other reactions of conjugated dienes as major reactants. 

In the presence of water, the reaction of tosylated y-aminoalkenes with PhaPAuSbFfi and Selectfluor afforded mixtures of 3-hydroxypiperidines and 2-hydroxymethylpyrrolidines. In this oxidative difunctionalization of the olefin, the 6-endo- cyclization products were formed predominantly (Scheme 4-71). Likewise,... 

In recent years, an alternative approach toward oxidative difunctionalization reactions of alkenes has become available. It uses a stepwise sequence of two different C-X bond-forming events. Palladium catalysis has proven to be most versatile in this context. While general difunctionahzation reactions with a substrate scope as broad as the AD reaction are still to be developed, the diversity with respect to functional group incorporation is already impressive. It is particularly important to note that these two-step processes of difunctionalization require different individual catalyst performance for each individual C-X bond formation. 

Li s copper-catalyzed oxidative difunctionalization of enol ethers with a-amino carbonyl compounds was recently reported (Scheme 2.9) [41]. This protocol allows rapid synthesis of 2-amino-3,4-dioxy carbonyl products. Significantly, metal-fiee, DTBP-mediated direct alkylation of a-amino carbonyl compounds with C—H bond of simple alkanes was developed by Cheng and co-workers [42]. 

Scheme 4.33 The aerobic oxidative difunctionalization of alkenes to 0x0 nitriles...

The bromination and oxidation of securinine have been reported (Scheme 87). Oxidative difunctionalization of 2-amino-4//-pyrans occurs with iodobenzene diacetate and A -chlorosuccinimide reagents. An oxidative rearrangement of [7]helicene by heating with iron(n) chloride and aluminium(III) chloride involves skeletal rearrangement with the loss of helicity (Scheme 88). ... 

Difunctionalization with similar or different nucleophiles has wide synthetic applications. The oxidative diacetoxylation of butadiene with Pd(OAc)i affords 1,4-diacetoxy-2-butene (344) and l,2-diacetoxy-3-butene (345). The latter can be isomerized to the former. An industrial process has been developed based on this reaction. The commercial process for l,4-diacetoxy-2-butene (344) has been developed using the supported Pd catalyst containing Te in AcOH. 1,4-Butanedioi and THF are produced commercially from 1,4-diacetoxy-2-butene (344)[302]. 

The Pd/MOP combination has proved active for the asymmetric hydrosilylation of cyclic alkenes and dienes. Thus treatment of norbornene with HSiCl3 at 0 °C for 24 h in the presence of 0.01 mol.% of M eO-MOIV[Pd(// -C3H5)Cl]2 gave quantitative yield of evo-2-(trichlorosilyl)norbornane oxidation produced the corresponding alcohol in 93% ee (Equation (12)). Lowering the temperature (to — 20 °C) increased this to a 96% ee. Both mono- and difunctionalization of nbd has proved possible, depending upon the quantity of trichlorosilane used (Scheme 22). In both reactions, extremely good enantioselectivities are observed 113... 

The desymmetrization works also well with higher substituted meio-epoxides such as ewdo-norbornene oxide (130) , cis-5,6- and 4,7-difunctionalized cyclooctene oxides 132 and 134, giving the alcohols 131, 133 and 135, respectively but for the diastereomer 136, the rearrangement to form the allylic alcohol 138 beside 137 cannot be completely suppressed (equation 29 best results are given). ... 

Aliphatic nitro compounds are versatile building blocks and intermediates in organic synthesis,14 15 cf. the overview given in the Organic Syntheses preparation of nitroacetaldehyde diethyl acetal.16 For example, Henry and Michael additions, respectively, lead to 1,2- and 1,4-difunctionalized derivatives.14 18 1,3-Difunctional compounds, such as amino alcohols or aldols are accessible from primary nitroalkanes by dehydration/1,3-dipolar nitrile oxide cycloaddition with olefins (Mukaiyama reaction),19 followed by ring cleavage of intermediate isoxazolines by reduction or reduction/hydrolysis.20 21... 

A widely applied strategy for the synthesis of various difunctionalized organic molecules, e.g. diols, dialdehydes, etc., relies on the oxidative cleavage of olelinic double bonds. Besides transition metal catalysis for asymmetric synthesis, periodate oxidation and ozonolysis are the standard tools for oxidative bond cleaving reactions. For economic and safety reasons, technically applicable alternatives to osmium-based chemistry and ozonolysis are of great interest. 

By oxidative C,C-bond cleavage on BDD electrodes phenanthrene (9) was transformed into the 1,F-difunctionalized biaryls 10 and 11, respectively (Fig. 5.7). Diester 11 was found to be the major product in all the experiments. 

To extend the synthetic scope of this new reaction, we have carried out the functionalization of the new 1,4-dilithiated derivatives 321 with different electrophiles. The obtained dihydropyrrole derivatives 322 or 323 could be easily oxidized to the corresponding 3,4-difunctionalized pyrroles, which present a pattern of substitution difficult to achieve by conventional methods (Scheme 82)141. 

However, in several cases palladium-assisted or -catalyzed [in the presence of an oxidant for palladium(O)] reactions produced 1,4-difunctionalization of dienes via initial anti addition of an amine to the monodentate diene palladium complex26-27. 

Completely regioselective additions of benzonitrile oxide to arylsulfinyl-5-alkoxyfuran-2(5//)-ones 403 and 406 gave rise to regioisomerie 4,5-difunctionalized isoxazoles 404 and 407, after spontaneous evolution of the primary adducts through desulfinylation and opening of the lactone ring. Subsequent condensation with hydrazine yielded isoxazolo-pyridazinones 405 and 408, obtained in 75% overall yield in a one-pot, two-step synthetic sequence (Scheme 98)... 

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