Allylic from alkenes

TT-Aliylpalladium chloride reacts with a soft carbon nucleophile such as mal-onate and acetoacetate in DMSO as a coordinating solvent, and facile carbon-carbon bond formation takes place[l2,265], This reaction constitutes the basis of both stoichiometric and catalytic 7r-allylpalladium chemistry. Depending on the way in which 7r-allylpalladium complexes are prepared, the reaction becomes stoichiometric or catalytic. Preparation of the 7r-allylpalladium complexes 298 by the oxidative addition of Pd(0) to various allylic compounds (esters, carbonates etc.), and their reactions with nucleophiles, are catalytic, because Pd(0) is regenerated after the reaction with the nucleophile, and reacts again with allylic compounds. These catalytic reactions are treated in Chapter 4, Section 2. On the other hand, the preparation of the 7r-allyl complexes 299 from alkenes requires Pd(II) salts. The subsequent reaction with the nucleophile forms Pd(0). The whole process consumes Pd(ll), and ends as a stoichiometric process, because the in situ reoxidation of Pd(0) is hardly attainable. These stoichiometric reactions are treated in this section. 

Preparing Alkyl Halides from Alkenes Allylic Bromination 339... 

Another method for preparing alkyl halides from alkenes is by reaction with jV-brotnosuccinimide (abbreviated NBS) in the presence of light to give products resulting from substitution of hydrogen by bromine at the allylic position—the position next to the double bond. Cyclohexene, for example, gives 3-bromo-cyclohexene. 

Simple alkyl halides can be prepared by radical halogenation of alkanes, but mixtures of products usually result. The reactivity order of alkanes toward halogenation is identical to the stability order of radicals R3C- > R2CH- > RCH2-. Alkyl halides can also be prepared from alkenes by reaction with /V-bromo-succinimide (NBS) to give the product of allylic bromination. The NBS bromi-nation of alkenes takes place through an intermediate allylic radical, which is stabilized by resonance. 

Alkynes react with indium reagents such as (allyl)3ln2l3 to form dienes (allyl substituted alkenes from the alkyne). Allyltin reagents add to alkynes in a similar manner in the presence of ZrCU Alkylzinc reagents add to alkynes to give substituted alkenes in the presence of a palladium catalyst. ... 

Hydrocarbons lacking directing substituents are not very reactive toward metal-lation, but it has been found that a mixture of n-butyllithium and potassium r-butoxide66 is sufficiently reactive to give allyl anions from alkenes such as isobutene.67... 

Monodehydrohalogenation of allylic halides is another classical method for diene synthesis24. This method is complementary to double dehydrohalogenation as both the 1,2-dihalides and allylic halides are readily accessed from alkenes. The commonly employed protocol for diene synthesis, particularly for cyclic 1,3-dienes, is through the allylic monobromination of the alkene with A-bromosuccinimide or related reagents followed by dehydrobromination with hindered bases such as DBN or DBU (equation l)25. 

Although the application of carboalumination to the synthesis of natural products is still in its infancy, a few preliminary results shown in Scheme 1.50 [167,168,171,172] suggest that it promises to become a major asymmetric synthetic reaction, provided that (i) the singularly important case of methylalumination can be made to proceed with S90% ee, and (ii) satisfactory and convenient methods for enantiomeric and diastereo-meric separation/purification can be developed. In this context, significant increases in ee in the synthesis of methyl-substituted alkanols from around 75 % to 90—93 % achieved through some strategic modifications are noteworthy (Scheme 1.50) [168]. Shortly before the discovery of the Zr-catalyzed enantioselective carboalumination, a fundamentally discrete Zr-catalyzed asymmetric reaction of allylically heterosubstituted alkenes proceeding via cyclic carbozirconation was reported, as discussed later in this section. 

Mixtures of allylic tosylamines are produced from alkenes and tosyliminoiodobenzene (PhI=NTos), generated in situ from iodobenzene and 4-toluenesulphonamide under the influence of manganese tetraphenylporphyrin, e.g. equation 74202. 

One may inquire whether the evidence that 77-allyl complexes yield desorbed olefins when formed from dienes and hydrogen, or from alkenes, is pertinent to the question concerning the course of the exchange of such complexes formed by the adsorption of saturated hydrocarbons. The composition of the surface must be different under the two circumstances in one there must be few sites not occupied by olefin or half-hydrogenated intermediates, while in the other (the exchange of saturated hydrocarbons) many sites must be vacant. Consequently, in the absence of an excess of any unsaturated hydrocarbon, there is no driving force for the desorption (or displacement) of the unsaturated intermediates which are formed on the surface and intermediates of any degree of unsaturation remain bonded to the surface and leave it only as saturated hydrocarbon. Yet the evidence obtained from the reactions of the unsaturated hydrocarbons must indicate the paths which may be traversed under either circumstance. 

A second type of organopalladium intermediates are 7r-allyl complexes. These complexes can be obtained from Pd(II) salts and allylic acetates and other compounds with potential leaving groups in an allylic position.79 The same type of 7i-allyl complexes can be prepared from alkenes by reaction with PdCl2 or Pd(02CCF3)2.80 The reaction occurs by electrophilic attack on the n electrons followed by loss of a proton. The proton loss probably proceeds via an unstable species in which the hydrogen is bound to... 

A number of methods for the preparation of vinyl and allyl sulfones are available [1U9, 110], and the syntheses of vinyl sulfones from alkenes has been reviewed [116]. A simple one-step procedure of wide applicability makes use of a palladium-catalysed cross-coupling reaction between aryl and alkyl sulfonyl chlorides and substituted vinyl and allyl stannanes... 

Benzylic halides can be prepared by the same radical-halogenating agents that give allylic halides from alkenes. These include Cl2, Br2, N-bromo-succinimide (Section 14-3A), S02C12, and im-butyl hypochlorite (see Exercise 4-18) ... 

The major focus in this chapter will be on synthesis, with emphasis placed on more recent applications, particularly those where regiochemistry and stereochemistry are precisely controlled. The reader is referred to the earlier reviews for full mechanistic information and details of historic interest. Electrophilic addition of X—Y to an alkene, where X is the electrophile, gives products with functionality Y (3 to the heteroatom X. Further transformations of X and/or Y provide the basis for diverse synthetic applications. These transformations include replacement of Y by hydrogen, elimination to form a ir-bond (either including the carbon bonded to X or (3 to that carbon so that X is now in an allylic position), and nucleophilic or radical substitution. Representative examples of these synthetic methods will be given below. This chapter will include examples of heterocycles formed in one-pot reactions where the the initial alkene-electrophile adduct contains an electrophilic group that can react further. Examples of heterocycles formed in several steps from alkene-electrophile adducts will also be considered. Cases in which activation by an external electrophile directly results in addition of an internal heteroatom nucleophile are treated in Chapter 1.9 of this volume. 

The reactivity of -Tr-allylpalladium-phosphine complexes generated stoichiometrically or from alkenes allylically substituted with a leaving group, is essentially identical and, as a result, allyl species will be generally considered in this section without distinction as to the origin of the palladium complex. 

In considering the diastereoselectivity associated with reactions of 7r-allylpalladium complexes, the stereochemical nature of two processes must be evaluated. The first is the formation of the ir-allylpalla-dium complex, and the second is the allylic functionalization of a nucleophile reacting with the allyl complex. As previously described (Section 3.3.2.1.1) the generation of ir-allyl complexes from alkenes by their reaction with stoichiometric amounts of palladium proceeds so as to leave the substituents on the allyl termini preferentially in the syn rather than the anti position and the palladium situated on the steri-cally less congested face of the allyl ligand, regardless of the stereochemistry of the starting alkene (12). 

Collins reagent is used for the introduction of carbonyl groups at allylic positions." This transformation of alkenes into enones is much slower than the oxidation of alcohols, requiring a great excess of Cr03 2Py and prolonged reaction times. Consequently, alcohols can be oxidized to aldehydes and ketones by Collins reagent without interference from alkenes. 

The direction of elimination of the /1-hydrogen to give either enol ethers or allylic ethers from alkenes can be controlled by using DMSO as a solvent. Formation of the allylic ether 47 was utilized in the synthesis of the tetronomycin precursor 47 from 46 [47], The oxidation of optically active 3-alkene-l,2-diol 48 afforded the 2,5-dihydrofuran 50 with high ee. It should be noted that /1-OH in 49 is eliminated to... 

Other methods for obtaining complexes of ethylene and other alkenes include ligand substitution reactions, reduction of a higher valent metal in the presence of an alkene, and synthesis from alkyl and related species [reductive elimination, of an allyl or hydride, for example hydride abstraction from alkyls protonation of sigma-allyls from epoxides (indirectly)] [74a],... 

Fig. 1.30. In some cases the allyl radical intermediate of Wohl-Ziegler brominations is available from alkene double bond isomers, which can profitably be used when one of the substrates is more easily accessible or cheaper than its isomer.

At high temperatures, both simplifications and complications of the above mechanism occur. Bimolecular initiation processes (involving at least one unsaturated molecule) cannot be excluded (see, for example, ref. 15). Transfer processes must be included since chains are no longer long. H abstraction from alkenes generates not only allylic type radicals, but also vinylic type radicals. As the temperature increases, allylic type radicals become thermally unstable. As the activation energy of unimolecular fissions of radicals is much higher than that of bimolecular processes such as metatheses, when the temperature increases the relative concentration of the p- radicals, compared with that of the thermally stable / and Y- radicals, decreases. Therefore, termination processes involve mainly / radicals (except for H- radicals, because they are very reactive and recombine in a third-order process) and Y-radicals. Finally, the addition of the most concentrated / and Y- radicals to unsaturated molecules can play a role, because this process is followed by a very fast unimolecular fission. For reasons of size limitation, the addition of radicals (e.g. H- and CH3-) will mainly be considered. Of course, the above a priori hypotheses about relative radical concentrations or reaction rates must be checked a posteriori, when numerical calculations have been carried out. 

Both chemical and enzymatic synthetic methods for the asymmetric oxidation of the carbon-carbon double bond have been developed [46], but the area of carbon-carbon double bond oxidations has been shaped by the breakthrough discovery of asymmetric epoxidation of allylic alcohols with the Katsuki-Sharpless method [47]. Catalytic asymmetric synthesis of epoxides from alkenes by Jacobsen... 

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