Other Addition Reactions

The addition of an alcohol molecule follows a similar pattern to the addition of water. Draw the mechanism for the addition of ethanol to ethanal under general acid catalysis conditions. 

Note that the positively charged oxonium ion intermediate has a canonical structure that is the alkyl equivalent of a protonated carbonyl species. The subsequent attack by the alcohol molecule and the loss of a proton are both fast steps. 

When this reaction is conducted on ketones, instead of aldehydes, the equivalent species to the hemiacetal and acetal are now called hemiketal and ketal respectively. However, when simple ketones are reacted with normal monofunctional alcohols, the reaction rarely goes to completion, unlike the situation with aldehydes where the reaction proceeds smoothly. Yet, when a 1,2-diol is reacted with a ketone, then the reaction goes to completion much more readily. Write the complete reaction sequence for the formation of the cyclic ketal starting from propanone and 1,2-ethandiol, under acidic conditions. Also, suggest why the product between one molecule of each reagent is favoured over the alternative product that would result from the reaction between two molecules of the diol and one of the ketone. 

Another very common addition reaction to the carbonyl group is that of the bisulphite anion. Historically, these derivatives are important, because as they readily yield a crystalline product, they are easily purified. Suggest the mechanism for this addition and hence the nature of the product. 

We will now turn our attention to the addition of carbon nucleophiles to the carbonyl group. This type of reaction represents a very important group of reactions that have wide synthetic utility, because they allow for the extension of the carbon backbone of the starting material. 

Other Addition Reactions.—At variance with previous reports, the palladium-catalysed reduction of 9a-fluoro-ll/3-hydroxy-A -and-A -corticosteroids proceeded stereospecifically to give the 5/8-isomers. The 9a-fluorine atom appears to be responsible for an increased folding of ring A towards the a-face, thus exposing the -face to the catalyst. 

Reaction of dimethyl acetylenedicarboxylate with A -compounds in boiling xylene gave the unstable Diels-Alder adducts (65) which rearranged by a retro-Diels-Alder reaction to the aromatic seco-compound (67). Using dicyanoacety-lene at lower temperature, the adducts (66) have been isolated and these were converted, in boiling xylene, into the analogous aromatic seco-compound (68). No 

Astier, A. Pancrazi, and Q. Khuong-Huu, Bull. Soc. chim. France, 1976, 1581. 

2 Other Addition Reactions - The photochemical addition in the gas phase of ammonia to a,P-unsaturated nitriles has been studied. The reactions are carried under conditions where all, or most, of the light is absorbed by the ammonia and this results in N-H bond fission and the production of NH2 radicals. These radicals add to the a-position of the substrate to yield 2-amino-propionitrile from acrylonitrile and analogous products are formed from crotononitrile, methacrylonitrile and 1-cyclohexenecarbonitrile. Additions also occur to but-2-yne nitrile which yields the Z, -isomers of 3-amino-crotononitrile with the E -isomer being predominant. The SET-induced amina-tion (using 1,4-dicyanobenzene as the sensitiser) of alkenylnaphthalene derivatives affords products of addition to both the alkene and the naphthalene skeleton. Suau et al. have examined the irradiation of phthalimide in the presence of low concentrations of hydroxide ion and alkenes. ° The result of this treatment is addition of the phthalimide moiety to the alkene. A SET 

Irradiation of the carbothioamides (75) in the presence of furan or some 2-substituted derivatives results in the formation of the pyrrole derivatives (76) with the R group being the original 2-substituent on the furan. The yields of products are variable and are shown below the structures. The key step in the 

Photoaddition reactions have also been described with (84) as the substrate.(2+2)-Photocycloaddition of simple alkenes to these enones results in the formation of the adducts (85) and phenylacetylene undergoes similar addition to this substrate. A substituent effect has been detected in these 

Photocycloaddition of 2-TMSO-buta-1,3-diene to enone (89) affords the adduct (90) which is a key intermediate in an approach to the synthesis of homoerythrinan alkaloids. The principal product obtained by irradiation (298-310 nm) of the dione (91) in the presence of the isoxazolone (92) has been identified as (93, 38%).  

Pyrex-filtered irradiation of methanol solutions of the pyridone (94) results in the formation of the (2+2)-cycloadduct (95). The route to (95) is thought to involve (4+4)-photocycloaddition to yield the adduct (96) which is thermally unstable and undergoes a facile Cope rearrangement to yield the cyclobutane isomer (95). A full account has been published of the photo-induced mixed addition between (97) and (98). A 1 1 ratio of these compounds yields the two adducts (99) and (100) in a 6 22 ratio. A 1 4 ratio of the reactants gives the same products but in a respective ratio of 21 6. 

Nakamura et al found that In(OTf)3 is effective in catalyzing the addition of carbon nucleophiles, 1,3-dicarbonyl compounds, to alkynes [95]. The reaction is 

New C-C bond formed at internal C amounts of EtsN of alkyne except R = and n-BuLi are SiMe2Ph required 

Yadav et al. made use of InCl3 adsorbed on silica gel to activate 1,3-dicarbonyl compounds for the addition to diethyl azodicarboxylate (DEAD) under microwave 

The use of transition metal catalysts to activate C-H bonds towards addition to C=0 and C=N bonds has been reviewed (64 references), with a focus on mechanistic data and lacunae.  

A range of cyclic alkenyl trifluoroacetates (120, = alkyl, allyl, benzyl = H, 6/7- 

MeO X = -CH2-, -OCH2- and -CH2CH2-) undergo enantioselective protonation, using methanol as proton source and a chiral binaphthyl tin bromide methoxide as chiral catalyst, to give chiral ketones (121). ° Pronounced nonlinear effects are observed in 0 the ee and are rationalized in terms of monomer-dimer equilibria involving the catalyst. 

An intrinsic reactivity index (IRI) has been developed, with a view to capturing electro-and nucleophilicity on a single scale, and using frontier molecular orbital data to access values. A correlation of IRI with Mayr s E and N parameters is also described. 

4-Addition of nucleophiles to a,j0-unsaturated carbonyl groups has been reviewed, considering acrylic amides or esters on a carbohydrate template as acceptors.  

The overall reaction is then represented by RH + S02 + Cl2—RS02C1 + HC1. 11.2.Id Other Addition Reactions 

Reactions, under irradiation, involving the addition to unsaturated hydrocarbons of nitrogen and phosphorus compounds and of silanes have been summarized by Spinks and Woods (1990). Some cycloaddition reactions have also been reviewed. These will not be detailed here. 

Decarboxylation of the pyrrolizinone-2-carboxylic acid gives very little of the parent pyrrolizinone instead 24 is produced when the anionic intermediate, formed on decarboxylation, adds in a Michael manner to the pyrrolizinone26 [Eq. (2)]. 

A review examines the role of chiral Brpnsted acids in enantioselective carbonyl activations (84 references). A short review describes the methods of generating secondary, tertiary, and quaternary carbon centres by geminal disubstitution of carbonyl oxygen, that is, C=0 CR R. Examples including reductive and alkylative ami- 

Reaction of a-haloketone with a nucleophile can give carbonyl addition, direct substitution, and proton abstraction. DFT calculations suggest that the reaction of hydroxide with a-bromoacetophenone (PhCOCH2Br) is a borderline case, with an addition/substitution TS, where hydroxide interacts with/bridges the two carbons. Such a TS could serve for two mechanisms, with path bifurcation after the TS, leading to the respective hydrate anion [Ph-C(0H)(0 )CH2Br] and substitution products 

DFT has been used to calculate pathways for the addition of hydroxide to cyclobutane-1,2-dione and to its hydrate, and addition of hydroxide ion to the carbonyl group of formyl heterocyclics has been studied by ab initio methods.  

Mass-resolved anionic products of the reaction of the radical, 0 , and acetaldehyde have been studied using photoelectron imaging. Several species have been assigned, but singlet formylmethylene (H-C-CHO) - a key intermediate in the Wolff rearrangement - proved elusive.  

The hydride affinities of 6 typical aldehydes and 15 typical ketones have been determined in acetonitrile. All are relatively weak hydride acceptors, but aldehyde values are typically larger by about 7 kcal mol aromatics are about 9 kcal moP larger than aliphatic analogues, whereas cyclic structures have slightly larger values (by 1-3 kcal moP ) than acyclics, and a-dicarbonyls show one of the strongest affinities ( 10 kcal moP more than related monocarbonyls).  

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Radiation cure system. Other addition reaction cure systems that have emerged in recent years are the ultra-violet (UV) and electron beam (EB) radiation cure systems. The development of these systems has been prompted by the ever-increasing need for fast cure rates and low cure temperatures. The U V cure system... 

Other addition reactions are shown in the scheme. Thus, Ceo reacts as an olefin towards [Pt (PPh3)2] to give the t adduct [Pt(>j -C6o)(PPh3)2]. Indeed six centres can simultaneously be coordinated by a single fullerene cluster to give [C6o M(PEt3)2 6], (M = Ni, Pd, Pt), with the 6M arranged octahedrally about the core. Likewise, reaction... 

Clearly, we must be able to predict when to expect a carbocation rearrangement. There are two common ways for a carbocation to rearrange either through a hydride shift or through a methyl shift. Your textbook will have examples of each. Carbocation rearrangements are possible for any reaction that involves an intermediate carbocation (not just for addition of HX across an alkene). Later in this chapter, we will see other addition reactions that also proceed through carbocation intermediates. In those cases, you will be expected to know that there will be a possibility for carbocation rearrangements. 

A variety of other addition reactions occurring regioselectively are also known. These include hydrocyanation, hydroalumination, hydrosilylation, and hydrozirconation. 

OTHER ADDITION REACTIONS 7.4.1 Further halogen derivatives... 

Among other addition reactions dienes undergo catalytic hydrogeneration (1,2- and 1,4-), epoxidation (1,2- only, and more slowly than the corresponding simple alkenes), but they seldom undergo hydration. 

The reaction is reversible, and cyanohydrin formation is more favoinable with aldehydes than with ketones, as with other addition reactions. The reverse reaction is easily effected by treating a cyanohydrin with aqueous base, since cyanide is a reasonable leaving group (see Section 6.1.4). 

Both the long C-C bond distance (1.50 A) and the very short Pt—C distances (2.0 A) indicate the strong interaction between the adsorbed molecule and the three platinum surface atoms. The covalent Pt—C distance would be 2.2 A. The shorter metal-carbon distances indicate multiple metal-carbon bonding that may be carbene or carbyne-like. Compounds with these types of bonds exhibit high reactivity in metathesis and in other addition reactions The carbon-carbon single bond distance indicates that the molecule is stretched as much as possible without breaking of this chemical bond. 

Other addition reactions Additions involving carbon Copper(I) chloride, 85 Lithium bis(dimethylphenyl-silyl)cuprate, 161 Manganese(III) acetate, 171 Mercury(II) chloride, 175 2-(Phenylseleno)acrylonitrile, 244 Threophos, 298 Additions involving nitrogen Benzeneselenenyl halides, 26 Additions involving oxygen Bis(Tj5-cyclooctadienyl)ruthe-nium(II), 35... 

Reduction and Other Addition Reactions Excluding Cycloaddition... 

Alkenes also undergo a variety of other addition reactions in which a reagent is added across the double bond. Hydration and hydrohalogenation are classic examples. 

Dihydropyrimidines 296 react very easily with water, forming 6-oxy derivatives 297 even during storage of 296 in solvents containing water and special catalysts [248]. There are examples of other addition reactions with water [326, 327, 328, 329, 330, 331], alcohols [82, 332], hydrazine and hydroxylamine [333]. 

The intermediate is called a carbinol-amine. (Most of the other addition reactions presented so far stop at this stage where the nucleophile has added to the carbonyl carbon and a proton has added to the oxygen.)... 

Apart from addition to alkenes and arenes, other addition reactions have also been observed ... 

Many other addition reactions are likely to involve an electrophilic mechanism via vinyl cations or bridged cationic species. A particularly interesting field which has been exploited for synthetic purposes but little understood from a detailed mechanistic viewpoint is that of the additions catalyzed by salts of mercury, silver and other metals (Winter-feld, 1969 Miocque et al. 1963). 

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