Pyrolytic syn Eliminations

Introduction
DP. C. Astles, S. V. Mortlock and E. J. Thomas, in Comprehensive Organic Synthesis, ed. B. M. Trost
and I. Fleming, vol. 6 (Oxford: Pergamon Press, 1991), p. 1011
DPyrolysis of carboxylic esters, xanthates, amine oxides, sulfoxides and selenoxides
DTakes place in a concerted manner (via cyclic TS) with syn stereochemical relationship in which
the hydrogen atom and the leaving group depart from the same side of the incipient double bond

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Esters
z

Introduction
DUsually effected at 300-500oC (Very high; Limitation of its usefulness !)
DCarried out by simple heating if bp is high enough,
DCarried out by passing the vapor through a heated tube
DThe absence of solvents and other reactants simplifies the isolation of the product
DEffective for the preparation of sensitive or reactive alkenes due to the absence of acidic or basic reagents

Transitions State
D6-Ring TS with syn-relationship of H and X

Regioselectivity and Stereoselectivity

DIn acyclic compounds, the regioselectivity is often poor
DThe composition of the products is determined mainly by the number of H atoms on each -carbon

DIn cyclic compounds, ring conformation is very important

D If there is a conjugating substituent in the -position, elimination occurs predominantly to give the
conjugated alkene

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Thionocarbonate & Xanthate

Introduction
DTakes place in the region of 150-250oC (Much lower T; 300-500oC in ester)
DSeparation of the alkene product from sulfur-containing by-products can sometimes be troublesome

Transitions State
D6-Ring TS with syn-relationship of H and X

Regioselectivity
DIn acyclic compounds, regioselectivity is often poor

Stereoselectivity
DIn acyclic compounds, (E)-alkene is obtained predominantly, although significant amounts of (Z)-isomer
are also observed

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tert-Amine Oxide (Cope Elimination)

z

Introduction
DPrepared by oxidation of tert-amine (with H2O2 or mCPBA)
DAlternative way to the Hofmann elimination of quaternary ammonium salt
DTakes place under relatively mild reaction conditions (100-200oC)
DAllow generation of C=C bond without subsequent migration into the conjugation systems

DIf an allyl or benzyl group is attached to the nitrogen atom, Meisenheimer rearrangement to give an
O-substituted hydroxylamine may compete with elimination
DA. C. Cope and E. R. Trumbull, Org. Reactions, 11 (1960), 317

Transition state
D5-Ring TS with syn-relationship of H and X

Regioselectivity and stereoselectivity

DIn acyclic compounds, the configuration of tertiary amine oxide determines the stereochemistry of the alkene
DIn cyclic compounds, ring conformation is very important

Application
DThe Cope elimination is reversible
DThe intramolecular reverse Cope elimination, involving the addition of a tethered hydroxylamine to an alkene,
has found recent application for the stereocontrolled preparation of cyclic amines
DE. Ciganek, J. Org. Chem., 60 (1995), 5803

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Regioselectivity ~ Ester (or Thionocarbonate or Xanthate) vs. t-Amine-oxide

Pyrolytic elimiation of 1-methylcyclohexyl derivatives

DThe acetates and xanthates give mixtures containing 1-methylcyclohexene and methylenecyclohexane
in a ratio of about 3:1
DPyrolysis of the oxide of 1-dimethylamino-1-methylcyclohexane gives methylenecyclohexane almost exclusively

DIn the 5-ring TS (amine oxide), preferential abstraction of H atom is allowed from the methyl group only
DIn the more flexible six-ring TS (ester pyrolyses), H atom abstraction is also possible from the ring

DWith larger, more-flexible rings, the cycloalkene is the major product from the amine oxides or the esters

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Sulfoxide

Introduction
DReadily obtained by oxidation of sulfides (mCPBA or NaIO4)
DSulfoxides with a -hydrogen atom readily undergo syn-elimination on pyrolysis
DTake place with a high syn-stereoselectivity
DAnother useful method for making C=C bonds

Transition state
D5-Ring TS with syn-relationship of H and X

Application
DA convenient method for introducing unsaturation at the position - to carbonyl compounds
DThe (E)-isomer usually predominates in reactions leading to 1,2-disubstituted alkenes

DB. M. Trost and T. N. Salzmann, J. Org. Chem., 40 (1975), 148

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Selenoxide

Preparation of selenide
DPrepared by a number of different methods
DMitsunobu reaction of alcohols with N-phenylselenophthalimide
(P. A. Grieco, J. Y. Jaw, D. A. Claremon and K. C. Nicolaou, J. Org. Chem., 46 (1981), 1215)
DSelenylation of an enolate with PhSeBr

Preparation of selenoxide
DReadily obtained from the corresponding selenides by oxidation

Reaction
DEven better methods than that of sulfoxide
DElimination occurs at rt or below, owing to the longer, weaker C-Se bond. In fact, preparation of selenoxde
and elimination normally occur together to give the alkene directly
DExploited for the preparation of a variety of different kinds of unsaturated compounds

Transition state
D5-Ring TS with syn-relationship of H and X

Regioselectivity
DIn acyclic compounds, the regioselectivity of selenoxide elimination can be poor

DIn cyclic compounds, ring conformation is very important

DElimination normally takes place preferentially away from an electronegative -substituent.

This allows a good method for converting epoxides into allylic alcohols by selenide-mediated epoxide opening
and subsequent oxidation/elimination sequence

D If there is a conjugating substituent in the -position, elimination occurs predominantly to give the
conjugated alkene

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Transformation of carbonyl compounds to ,-unsaturated carbonyl compounds

DSelenide (and sulfide) stabilize an -carbanion
DAlkylation of selenide followed by elimination provides a route to ,-unsaturated carbonyl compounds
(H. J. Reich and S. Wollowitz, Org. Reactions, 44 (1993), 1)

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-Hydroxy selenide

Preparation
DH. J. Reich, F. Chow and S. K. Shah, J. Am. Chem. Soc., 101 (1979), 6638
DA. Krief, Tetrahedron, 36 (1980),2531
DThe -hydroxy selenides can be prepared by a number of methods
DReduction of -seleno aldehydes or ketones
DAddition of a Grignard reagent to -seleno aldehydes or ketones
DAddition of -lithio selenides to aldehyde

Reaction
DHigh yields of di-, tri- or tetrasubstituted alkenes can be obtained
DAlternative route to the Wittig reaction when the phosphonium salt cannot be readily obtained
DProceeds under the action of MsCl, SOCl2, or other appropriate activating conditions

Transition state
DProceeds by stereospecific anti-elimination to the episelenonium ion, and then by syn-elimination of
the episelenonium ion to the alkene

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