Pyrolytic Syn Eliminations

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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


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



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


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



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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Pyrolytic Syn Eliminations

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