Intermolecular addition-elimination

The reaction of 1,2-benzoquinones with 1,2-diamines gives p3zrazine derivatives, but examples since 1980 are very limited. For example, reaction of the diamine 89 with 1,2-benzoquinone gives the 2,3-di-p-tolylquinoxaline 90 (equation (10)) (85JA1501). In a similar way, a 

A similar transformation, this time involving a decarboxylation step, occurs with a-amino acids (equation (12)), but it should be noted that complex mixtures were obtained using other, less-hindered, quinones 

Orf/io-chloranil 8 and diethylphosphorylmethyl methyl sulphoxide [(EtO)2PO.CH2SO.Me] (2 equiv.) give a tetrachloro-2,3-dihydrobenzofuran derivative (55%) (98SC3579). 

2 Six-membered ring formation. Reactions of orf/io-quinones with l-(dimethylamino)-but-3-ene-l-)me (80MI29) and ethyl diethoxyphosphor-ylacetate (92PS241) have been reported to give benzo[6]pyran derivatives. 

3 Seven-membered ring formation. Reaction of 3,5-di-7-butyl-l,2-benzoquinone with 1-phenylcyclopropylamine gives a mixture of the 

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A polyfluorinated P,y-unsaturated ketone is formed m situ from tributylamine and 3,4-bis(tnfluoromethyl)-3-(pentafluoroethyl)-5,5,6,6,6-pentafluoro-2-hex-anone. The enol form of the unsaturated ketone cyclizes via an intermolecular addition-elimination reaction that involves exclusive attack by oxygen rather than by carbon. This reaction demonstrates the hardness of a F-C= site toward... 

West et al. have recently described the synthesis and reactions of a 1-germaallene. Germaallene 76 (Eq. (7)) is analogous to silaallene 59a and is synthesized by intermolecular addition of f-butyllithium to precursor 75, followed by salt elimination at —78 C. This germaallene is not stable above 0 C in solution, but remains intact until heated above 90°C in the solid state. In either case, the... 

Although the high reactivity of metal-chalcogen double bonds of isolated heavy ketones is somewhat suppressed by the steric protecting groups, Tbt-substituted heavy ketones allow the examination of their intermolecular reactions with relatively small substrates. The most important feature in the reactivity of a carbonyl functionality is reversibility in reactions across its carbon-oxygen double bond (addition-elimination mechanism via a tetracoordinate intermediate) as is observed, for example, in reactions with water and alcohols. The energetic basis... 

For neutral nucleophiles (e.g. amines, alcohols, water) there is much evidence that the addition-elimination mechanism depicted in equation 1 fits very well most of the intermolecular and intramolecular nucleophilic displacements involving nitro-activated aromatic substrates1. 

Kita has introduced a novel one-pot preparation of 5-methoxylated indoline 55 and indole 56 derivatives by intermolecular addition followed by cyclization between A-tosylaniline derivatives 53 and activated olefins 54 using phenyliodine(III) bis(trifluoroacetate) (FIFA) <99H511785>. In the reaction of 53 with phenyl vinyl sulfides, indoles were produced directly by the spontaneous elimination of thiophenol. 

Mechanistic studies of the rearrangement activity of the ring-opening metathesis polymerization catalyst [Ru(H20)6]2+ were reported for unfunctionalized alkenes (112). The mechanism was found to be intermolecular, the alkene isomerization proceeding through an addition-elimination mechanism with a metal hydride catalytic species. This interpretation was... 

Padwa and Dehm62 have prepared furanones (36) by reaction of carbox-ylates with bromo aldehydes, catalyzed by 18-crown-6. The first step of the reaction is also an esterification of the potassium phenylacetate the next step is equivalent to an intermolecular addition of a carbanion to an aldehyde, followed by elimination. 

The proposed mechanism of the isomerization of polyfluorooxiranes to ketones does not involve a 1,2-fluorine shift, but rather coordination of the Lewis acid with the epoxide oxygen, ring opening to the carbocation, and intermolecular addition and elimination of fluoride.29 45... 

From our discussion of intermolecular additions, we would not expect these cyclizations of carbon radicals to occur in the elimination direction, and indeed cyclic radicals in five-membered or larger rings do not ordinarily open according to Equation 9.115. If the ring is small or highly strained, on the other hand,... 

Redox and homolytic substitution reactions almost never directly form C—C, C—N and C—O bonds. Such bonds are generated in radical addition reactions (Scheme 14). Intermolecular addition reactions are presented in this chapter. Cyclization reactions have important similarities with, and differences from, bimolecular additions, and they are presented in Chapter 4.2 of this volume. Falling under the umbrella of addition reactions are radical eliminations (the reverse of addition) and radical migrations (which are usually, but not always, comprised of an addition and an elimination). 

As a combined reaction of (3-cleavage of a cyclopropylcarbinyl radical and intermolecular addition, treatment of vinylcyclopropane (266) and activated alkyne in the presence of PhSSPh and AIBN forms a cyclopentene skeleton (267), through the initial addition of a thiyl radical to the vinyl group, P-cleavage of the cyclopropylcarbinyl radical, addition of the carbon-centered radical to the alkyne, ring closure of a vinyl radical via 5-exo-trig manner, and finally subsequent P-elimination of the thiyl radical, as shown in eq. 3.107 [272-276]. Here, PhSSPh acts as a catalyst, since the thiyl radical is regenerated. Aliphatic disulfides such as... 

The second step, between 400°C and 800°C is exothermic. In this step, elimination of HCI takes place from the polyene at a lower rate since chlorine atoms linked to unsaturated carbon atoms are involved which gives a more thermally stable bond than chlorine-saturated carbon of the original chloroparaffin. Intermolecular addition, responsible for the exothermic effect, takes places between double bonds leading to cross-linked products46 and possibly to aromatization. 

Unlike many other type of radical addition reactions, the product is most often an alkyl-cobalt(III) species capable of further manipulation. These product Co—C bonds have been converted in good yields to carbon-oxygen (alcohol, acetate), carbon-nitrogen (oxime, amine), carbon-halogen, carbon-sulfur (sulfide, sulfinic acid) and carbon-selenium bonds (equations 179 and 180)354. Exceptions to this rule are the intermolecular additions to electron-deficient olefins, in which the putative organocobalt(III) species eliminates to form an a,/ -unsaturated carbonyl compound or styrene353 or is reduced (under electrochemical conditions) to the alkane (equation 181)355. 

Mechanistically, this sequence is an interplay of intra- and intermolecular events featuring four cyclizations, one hydrogen transfer, one /1-elimination and an intermolecular addition. In this chapter, we will deal with the recent developments of these different aspects in the hterature since 2000, as the two volumes edited by Philippe Renaud and Mukund Sibi have covered the literature prior to 2000 [2]. 

The fundamental differences between these two mechanisms are that 1) the jr-allyl metal hydride mechanism involves a 1,3-hydrogen shift while the metal hydride addition-elimination mechanism involves a 1,2-hydrogen shift and 2) the hydrogen shift in the Jt-allylhydride mechanism proceeds in an intramolecular fashion while that in the metalhydride addition-elimination mechanism proceeds in an intermolecular fashion. 

The crossover product, propionaldehyde-l,3-d-3- C 12, clearly demonstrated that the isomerization occurred via intermolecular 1,3-hydrogen shift. These results are consistent with a modified metal hydride addition-elimination mechanism which involves exclusive 1,3-hydrogen shift through oxygen-directed Markovnikov addition of the metal hydride to the carbon-carbon double bond (Scheme 12.2). The directing effect of functional groups on the selectivity of transition metal catalysis is well presented [9], and an analogous process appears to be operative in the isomerization of allylamines to enamines [10]. 

At very low concentration levels, the mode MONOMOLEC is used, which additionally eliminates the intermolecular reactions and considers only monomolecular or pseudo-monomolecular reactions of the starting materials. 

The intermolecular addition of O-acyl thiohydroxamates to alkenes with concomitant displacement of a chain-carrying vinyl radical (i.e. the addition -elimination strategy) [31, 42] is also a very useful carbon-carbon bond-forming reaction as shown in Scheme 39. However, a necessary prerequisite for an efficient chain sequence is the incorporation of an electron withdrawing group at the central carbon atom of the allylic unit. 

C-Glycopyranosides may be obtained from glycopyranosyl halides via intermolecular addition of glycopyranosyl radicals [129]. In a more useful example, the a-aminoacrylate 192 was used as the radical acceptor for preparation of C-glycosyl amino acids 193 and 194 [130] (Scheme 66). In a concise synthesis of showdomycin (197), Barton utilized the trigger reaction of the 7V-hydroxy-2-thiopyridone derivative and the exceptional radicophilicity of tellurides in concocting the conditions for the conversion from the anisyl telluride 195 to the intermediate 196 after oxidative elimination [131] (Scheme 67). In Keck s synthesis of (-t-)-pseudomonic acid C (201), the intermediate 200 was prepared via stereocontrolled intermolecular addition of the radical generated from the iodide 198 to the allylic sulfone 199 [132] (Scheme 68). 

Although it is generally agreed that rotation about 0 occurs in most cases, it is relatively difficult to prove this point and two caveats are in order (1) intermolecular exchange can produce NMR spectra very similar in nature to rotation (especially in coordinatively unsaturated d complexes) and (2) addition-elimination reactions can produce an identical interchange of protons. Retention of coupling constants to the spin of the metal in complexes and those... 

In an analogous manner to quinazolines (86H(24)1243), 1,2,4-triazines can be readily dimerised in the presence of KCN to produce bi-l,2,4-triazines. This nucleophilic addition-elimination transformation can be carried out in both an intermolecular (08TL719, 07EJO3414, 05MOL274) and an intramolecular (08TL723) fashion (Scheme 14). 

Some examples of intermolecular addition of carbon-centred radicals, followed by -elimination of tin or sulfur radicals were provided in Schemes 4.38-4.43 and this strategy is effective in intramolecular processes. Thus, in a synthesis of the antitumor agent CC-1065, the aryl radical generated from the bromide 66 underwent cyclization and subsequent p-ehmination to give the indoline 67 (4.59). An advantage of this type of elimination procedure is that it provides a new alkene in a defined position that is suitable for further elaboration. The p-elimination of a sulfur radical has found other applications, such as in syntheses of the alkaloid morphine and the neuroexcitatory amino-acid kainic acid. ... 

Phenyl-1-propyne (55) underwent facile formal intermolecular hydroamination, affording the allylic amine 56 in high yield at 0 "C in the presence of AcOH or benzoic acid. In this reaction, at first, Pd-catalyzed isomerization of 55 to pheny-lallene (57) occurs by addition-elimination of H-Pd-OAc to internal alkyne 55, and then the allene 57 is converted to jr-allylpalladium intermediate 58 by hydropal-ladation. The final step is a well-known amination to produce the allylic amine 56. As an intramolecular version, 2-(2-phenylpropenyl)pyrrole (60) was obtained from l-phenyl-7-amino-l-hexyne 59 [16,16a]. Similarly Pd/benzoic acid-catalyzed hydroalkoxylation of 55 with (—)-menthol (61) afforded the allylic ether 62 [17]. 

During the following several years, many examples of organocatalytic tandem reactions such as the intramolecular a-alkylation step were developed, but they are not subjected in this chapter [113]. Unlike any yet published example of intermolecular a-alkylation of aldehydes and ketones via an Sat2 mechanism, several works via the SAr2 -type addition-elimination pathway were disclosed to date. 

Carbene complexes can also react by addition of alkane C-H bonds across the M=Cbond to generate a product containing two metal-carbon single bonds or materials derived from such products. This reaction is the reverse of the a-elimination, which is a common reaction that forms Schrock-t5q5e carbene complexes, as noted in Chapters 3,10, and 13. Such reactions of carbene complexes with the C-H bonds of alkyl groups were first observed to occur intramolecularly, particularly after generation of cationic carbene complexes. " However, intermolecular additions of C-H bonds of arenes ° and alkanes are also known. 

Intermolecular addition of alcohols to catalytic ruthenium vinylidenes is far more difficult than the addition of water except when allylic alcohols are employed (Scheme 9) [92-96]. In this case, the reaction of an allylic alcohol with a terminal alkyne catalyzed by CpRuCl(PPh3)2 afforded a p,Y-unsaturated ketone. The initial ruthenium oxacarbene obtained by addition of the alcohol to the ruthenium vinylidene evolves through a Claisen rearrangement to a Jt-allyl ruthenium species. Reductive elimination then gives rise to the final unsaturated ketone. 

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