Diazomethane reaction, transition states

The regioselectivity of 1,3-dipolar cycloadditions can also be analyzed by MO calculations on transition-state models. For example, there are two possible regioisomers from the reaction of diazomethane and methyl vinyl ether, but only the 3-methoxy isomer is formed. 

Mechanistically the 1,3-dipolar cycloaddition reaction very likely is a concerted one-step process via a cyclic transition state. The transition state is less symmetric and more polar as for a Diels-Alder reaction however the symmetry of the frontier orbitals is similar. In order to describe the bonding of the 1,3-dipolar compound, e.g. diazomethane 4, several Lewis structures can be drawn that are resonance structures ... 

The Simmons-Smith reaction " and its variants are widely used for the stereospecific synthesis of cyclopropane compounds. The methodology involves the use of copper-treated zinc metal (the zinc-copper couple) with diiodomethane to add methylene to a carbon-carbon double bond. Alternative use of diazomethane in catalytic reactions does not offer the same synthetic advantages and is usually avoided because of safety considerations. As significant as is the Simmons-Smith reaction for cyclopropane formation, its employment for organic synthesis was markedly advanced by the discovery that allylic and homoallylic hydroxyl groups accelerate and exert stereochemical control over cyclopropanation of alkenes (e.g, Eq. 21), and this acceleration has been explained by a transition state model... 

In the somewhat related reaction of glycopyranosiduloses with diazomethane, spiro-epoxides were the major products, but reaction with diazoethane gave ring-expansion products exclusively.170 The formation of the latter was rationalized in terms of nonbonded interactions in the transition states leading to spiro-epoxides. It was also considered that steric effects determine which of the two ring-expansions possible occur. 

Evidence that the actual methylation of the anion can be divided into SN1, Eq. (3), and SN2 types, Eq. (4), is provided by a whole series of investigations.1119 The terms SN1 and SN2 must be taken to mean reactions with, respectively less or greater nucleophilic participation of the anion in the transition state. The importance of oriented ion pairs in the solvents of low polarity frequently used in reactions involving diazomethane, e.g., the ions formed by a diazoalkane and benzoic acid in ether, should be emphasized. The expression oriented ion pair means that, because of insufficient solvation, the ions are not individually solvated but exist as ion pairs within a solvent cage.11 20 21 The orientation within the ion pair is defined electrostatically, and this orientation fixes the path for the product-determining step. Several indications (cf. footnotes 22-24) in the literature indicate the occurrence of carbonium ions and oriented ion pairs in Broensted-type equilibria of the type of Eq. (2). 

Reactions involving a five-membered transition state are even more favoured on entropy grounds, although there is some angle strain in the transition state and the products. The first step in the reaction of ozone with alkenes is a reaction of this type (7.5), as is the reaction of diazomethane with alkenes such as methyl acrylate (methyl propenoate) (reaction 7.6). In each case, six p-type electrons are involved, a Hiickel number, so the reactions will be favoured as long as the reactions are entirely suprafacial. The movement of three pairs of electrons (six in total) is shown by the curved arrows, and corresponds to the bonds broken and formed during these two reactions. 

Matsuoka and Szwarc (1961) photolyzed diazomethane in the presence of isooctane and styrene in one case, and in the presence of isooctane and styrene-a,j8,j8-d3 in the other case, and thus determined the methyl affinities of styrene and of trideuteriostyrene with respect to isooctane by the method of competing reactions. The isotope effect ( d/ h) was 1-07-1 ll. Matsuoka and Szwarc used these data to justify the conclusion that in radical addition reactions the initial structure of a reactive center is preserved in the transition state. In styrene and in trideuteriostyrene the reactive centers are both terminal carbon atoms doubly bonded to another carhon. In the product the reactive carbon atom becomes tetrahedral, and thus the transition state could conceivably resemble either reactant (trigonal) or product (tetrahedral). It can be calculated, however, that a change of configuration from trigonal to tetrahedral in the transition state should exhibit an isotope effect kj)jk ) of about 1-8 in the reactions studied by Matsuoka and Szwarc the tetrahedral configuration was therefore excluded by these authors. 

Nitrile oxides add in a 1,3-dipolar fashion to the double bond of cyclopropenes and diazomethane adds to give a pyrazoline (729) in good yield. Phenyl azide shows a very fast rate of reaction with 3,3-dimethylcyclopropene compared with additions to other olefins, evidently due to the influence of strain release in lowering the transition state of reaction, but the initial adduct is not stable and undergoes a reverse... 

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