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Pyrolytic syn Eliminations
Introduction
P. C. Astles, S. V. Mortlock and E. J. Thomas, in Comprehensive Organic Synthesis, ed. B. M. Trostand I. Fleming, vol. 6 (Oxford: Pergamon Press, 1991), p. 1011
Pyrolysis of carboxylic esters, xanthates, amine oxides, sulfoxides and selenoxides
Takes 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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Transitions State
Esters
Usually effected at 300-500 oC (Very high; Limitation of its usefulness !)
Carried out by simple heating if bp is high enough,
6-Ring TS with syn -relationship of H and X
Introduction
Regioselectivity and Stereoselectivity
In acyclic compounds, the regioselectivity is often poor
The composition of the products is determined mainly by the number of H atoms on each -carbon
In cyclic compounds, ring conformation is very important
If there is a conjugating substituent in the -position, elimination occurs predominantly to give the
conjugated alkene
Carried out by passing the vapor through a heated tube
The absence of solvents and other reactants simplifies the isolation of the product
Effective for the preparation of sensitive or reactive alkenes due to the absence of acidic or basic reagents
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Introduction
Thionocarbonate & Xanthate
6-Ring TS with syn -relationship of H and X
Transitions State
Takes place in the region of 150-250 oC (Much lower T; 300-500 oC in ester)
Separation of the alkene product from sulfur-containing by-products can sometimes be troublesome
In acyclic compounds, regioselectivity is often poor
Regioselectivity
Stereoselectivity
In acyclic compounds, (E)-alkene is obtained predominantly, although significant amounts of (Z)-isomer
are also observed
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Introduction
tert -Amine Oxide (Cope Elimination)
If an allyl or benzyl group is attached to the nitrogen atom, Meisenheimer rearrangement to give an
O-substituted hydroxylamine may compete with elimination
Prepared by oxidation of tert -amine (with H 2O2 or mCPBA)
A. C. Cope and E. R. Trumbull, Org. Reactions, 11 (1960), 317
In acyclic compounds, the configuration of tertiary amine oxide determines the stereochemistry of the alkene
Regioselectivity and stereoselectivity
The Cope elimination is reversible
The 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
Application
E. Ciganek, J. Org. Chem., 60 (1995), 5803
In cyclic compounds, ring conformation is very important
5-Ring TS with syn -relationship of H and X
Transition state
Allow generation of C=C bond without subsequent migration into the conjugation systems
Alternative way to the Hofmann elimination of quaternary ammonium salt
Takes place under relatively mild reaction conditions (100-200 oC)
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Pyrolytic elimiation of 1-methylcyclohexyl derivatives
The acetates and xanthates give mixtures containing 1-methylcyclohexene and methylenecyclohexane
in a ratio of about 3:1
Pyrolysis of the oxide of 1-dimethylamino-1-methylcyclohexane gives methylenecyclohexane almost exclusively
Regioselectivity ~ Ester (or Thionocarbonate or Xanthate) vs. t-Amine-oxide
In the 5-ring TS (amine oxide), preferential abstraction of H atom is allowed from the methyl group only
In the more flexible six-ring TS (ester pyrolyses), H atom abstraction is also possible from the ring
With larger, more-flexible rings, the cycloalkene is the major product from the amine oxides or the esters
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Introduction
Readily obtained by oxidation of sulfides (mCPBA or NaIO 4)
Sulfoxide
A convenient method for introducing unsaturation at the position - to carbonyl compounds
The ( E )-isomer usually predominates in reactions leading to 1,2-disubstituted alkenes
B. M. Trost and T. N. Salzmann, J. Org. Chem., 40 (1975), 148
Application
5-Ring TS with syn -relationship of H and X
Transition state
Sulfoxides with a -hydrogen atom readily undergo syn -elimination on pyrolysisTake place with a high syn -stereoselectivity
Another useful method for making C=C bonds
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Preparation of selenoxide
Readily obtained from the corresponding selenides by oxidation
Selenoxide
Reaction
Even better methods than that of sulfoxideElimination 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
Exploited for the preparation of a variety of different kinds of unsaturated compounds
Preparation of selenide
Prepared by a number of different methods
Regioselectivity
In acyclic compounds, the regioselectivity of selenoxide elimination can be poor
Mitsunobu 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)
Selenylation of an enolate with PhSeBr
Transition state
5-Ring TS with syn -relationship of H and X
In cyclic compounds, ring conformation is very important
If there is a conjugating substituent in the -position, elimination occurs predominantly to give the
conjugated alkene
Elimination 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
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Selenide (and sulfide) stabilize an -carbanion
Transformation of carbonyl compounds to ,-unsaturated carbonyl compounds
Alkylation 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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H. J. Reich, F. Chow and S. K. Shah, J. Am. Chem. Soc., 101 (1979), 6638
A. Krief, Tetrahedron, 36 (1980),2531
Preparation
The -hydroxy selenides can be prepared by a number of methods
Proceeds by stereospecific anti -elimination to the episelenonium ion, and then by syn -elimination of the episelenonium ion to the alkene
High yields of di-, tri- or tetrasubstituted alkenes can be obtained
Alternative route to the Wittig reaction when the phosphonium salt cannot be readily obtained
Reduction of -seleno aldehydes or ketones
Addition of a Grignard reagent to -seleno aldehydes or ketones
Addition of -lithio selenides to aldehyde
-Hydroxy selenide
Reaction
Transition state
Proceeds under the action of MsCl, SOCl 2, or other appropriate activating conditions
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