Eliminations Involving Cyclic Transition States

Reactant Transition state Product Temp, range Ref. 

Amine oxide pyrolysis occurs at temperatures of 100-150 C. The reaction can proceed at room temperature in DMSO. If more than one type of -hydrogen can attain the eclipsed conformation of the cyclic transition state, a mixture of alkenes will be formed. The product ratio should parallel the relative stability of the competing transition states. Usually, more of the -alkene is formed because of the additional eclipsed interactions present in the transition state leading to the Z-alkene. The selectivity is usually not high, however. 

Selenoxides are even more reactive than amine oxides toward p elimination. In fact, many selenoxides react spontaneously when generated at room temperature. Synthetic procedures based on selenoxide eliminations usually involve synthesis of the corresponding selenide followed by oxidation and in situ elimination. We have already discussed examples of these procedures in Section 4.7, where the conversion of ketones and esters to their a,/8-unsaturated derivatives was considered. Selenides 

Alcohols can be converted to o-nitrophenyl selenides by reaction with o-nitrophenyl selenocyanate and tri-n-butylphosphine.  

The selenides prepared by any of these methods can be converted to selenoxides by such oxidants as hydrogen peroxide, sodium metaperiodate, peroxycarboxylic acids, t-butyl hydroperoxide, or ozone. 

The cyclic nature of the transition states in these reactions dictates that elimination will proceed with syn stereochemistry. A cyclic transition state involving only five or six atoms cannot accommodate an anti stereochemical relationship at the site of elimination. For this reason, this family of reactions is often referred to as thermal syn eliminations. 

Amine oxide pyrolysis occurs under milder conditions than any of the other 

Under the mild conditions of the reaction, there is no equilibration of the alkenes, so the product composition is governed by the relative stabilities of the various transition states. Usually, more of the trans olefin than of its cis isomer is formed, presumably because steric repulsion raises the energy of the transition state leading to cis olefin. The selectivity is not high, however, since the ratio of trans cis from some simple cases is in the range 3 1 to 2 1. In cyclic systems, conformational 

The pyrolysis of esters has usually been done with acetate esters. The thermal requirement for the reaction is very high, with temperatures above 500° usually required. The pyrolysis is thus a vapor-phase reaction. In the laboratory, this is usually accomplished in a packed glass tube heated with a small furnace. The reacting vapors and product are swept through the hot chamber at an appropriate rate by an inert gas such as nitrogen, and into a cold trap or other system for condensation. 

Similar reactions occur with esters derived from long-chain acids if the boiling point of the ester is high enough, the reaction can be carried out in the liquid phase. Vapor-phase acetate pyrolysis is, however, the most generally used procedure. 

In cyclic systems, conformational effects and the requirement for a cyclic transition state determine the product composition. This effect can be seen in the product ratios from pyrolysis of iV,iV-dimethyl-2-phenylcyclohexylamine 7V-oxide. 

Elimination to give a double bond conjugated with an aromatic ring is especially favorable. This presumably reflects both the increased acidity of the proton a to the phenyl ring and the stabilizing effect of the developing conjugation at the transition state. Amine oxides 

Selenoxides are even more reactive than amine oxides toward p elimination. In fact, many selenoxides react spontaneously when generated at room temperature. Synthetic procedures based on selenoxide eliminations usually involve synthesis of the corresponding selenide followed by oxidation and in situ elimination. We have already discussed examples of these procedures in Section 4.7, where the conversion of ketones and esters to their a,j5-unsaturated derivatives was considered. Selenides can also be prepared by electrophilic addition of selenenyl halides and related compounds to alkenes (see Section 4.5). Selenide anions are powerfiil nucleophiles that can displace halides or tosylates and open epoxides. Selenide substituents stabilize an adjacent carbanion so that a-selenenyl carbanions can be prepared. One versatile procedure involves conversion of a ketone to a bis-selenoketal which can then be cleaved by w-butyllithium. The carbanions in turn add to ketones to give jS-hydroxyselenides. Elimination gives an allylic alcohol. 

Selenide anions are powerful nucleophiles that can displace halides or tosylates and open epoxides.233 Selenide substituents stabilize an adjacent carbanion so that a-selenenyl carbanions can be prepared. One versatile procedure involves conversion of a ketone to a bis-selenoketal which can then be cleaved by w-butyl lithium.234 The carbanions in turn add to ketones to give /f-hydroxyselenides.235 Elimination gives an allylic alcohol. 

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If the reaction between cinnamate 1 and hydroxylamines occurred through a concerted mechanism, the process should take place through a cyclic (five-mem-bered ring) transition state, similar to the ones proposed for [3+2] dipolar cycloadditions or retro-Cope eliminations. The cyclic transition state for the concerted addition of deuterated iV-methylhydroxylamine to ethyl cinnamate 1 is represented in Scheme 8.7 (atoms involved in the cyclization colored blue). As the nitrogen atom and the deuterium approach the C=C bond from the same side, the addition is syn, leading to intermediate 12. A rapid proton shift would give compound 3 which can be either isolated or cyclized in the presence of a Lewis acid to the isoxazolidi-none 4 by intramolecular transesterification. The stereochemistry of the products 3 and 4 is determined during the concerted addition step. 

Several types of compound undergo elimination on heating, with no other reagent present. Reactions of this type are often run in the gas phase. The mechanisms are obviously different from those already discussed, since all those require a base (which may be the solvent) in one of the steps, and there is no base or solvent present in pyrolytic elimination. Two mechanisms have been found to operate. One involves a cyclic transition state, which may be four, five, or six membered. Examples of each size are... 

The other SiH4 decomposition pathway involves Hj elimination via a three-center cyclic transition state (Roenigk et ai, 1987) ... 

Another important family of elimination reactions has as the common mechanistic feature cyclic transition states in which an intramolecular proton transfer accompanies elimination to form a new carbon-carbon double bond. Scheme 6.16 depicts examples of the most important of these reaction types. These reactions are thermally activated unimolecular reactions that normally do not involve acidic or basic catalysts. There is, however, a wide variation in the temperature at which elimination proceeds at a convenient rate. The cyclic transition states dictate that elimination occurs with syn stereochemistry. At least in a formal sense, all the reactions can proceed by a concerted mechanism. The reactions, as a group, are referred to as thermal syn eliminations. 

A unimolecular elimination involving a semi-polar five-membered cyclic transition state (81) (Scheme 9, R1 = Ph, R2 = R3 = H) appears to account for the formation of benzaldehyde, CO, and H2O on eliminative fragmentation of mandelic acid in the gas phase.44 The same type of transition state has been proposed for gas-phase pyrolysis of ROCH2COOH (R = MeO, EtO, and Ph O) with corresponding formation of ROH, CO, and formaldehyde the rate of reaction is little dependent on R.45... 

Phenoxypropanoic acid, 3-(phenylthio)propanoic acid, 4-phenylbutanoic acid and the corresponding ethyl and methyl esters have been pyrolysed between 520 and 682 K.10 Analysis of the pyrolysates showed the elimination products to be acrylic acid and the corresponding arene. The thermal gas-phase elimination kinetics and product analysis have been found compatible with a thermal retro-Michael reaction pathway involving a four-membered cyclic transition state. 

The kinetics of the gas-phase elimination of 3-hydroxy-3-methylbutan-2-one have been investigated in a static system, seasoned with allyl bromide, and in the presence of the free chain radical inhibitor toluene.14 The reaction was found to be homogeneous, unimolecular and to follow a first-order rate law. The products of elimination are acetone and acetaldehyde. Theoretical estimations suggest a molecular mechanism involving a concerted non-synchronous four-membered cyclic transition state process. 

Cope elimination occurs under milder conditions than Hofmann elimination. It is particularly useful when a sensitive or reactive alkene must be synthesized by the elimination of an amine. Because the Cope elimination involves a cyclic transition state, it occurs with syn stereochemistry. 

Similar steps have been proposed for other acylphosphates " . Reaction (1) could involve a cyclic transition state including proton transfer. For the dianion, elimination of cyanic acid, viz. 

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