Pyrolytic syn Eliminations

Introduction P. 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 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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Esters Introduction Usually effected at 300-500oC (Very high; Limitation of its usefulness !) Carried out by simple heating if bp is high enough, 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

Transitions State 6-Ring TS with syn-relationship of H and X

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

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Thionocarbonate & Xanthate

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

Transitions State 6-Ring TS with syn-relationship of H and X

Regioselectivity In acyclic compounds, regioselectivity is often poor

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

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

Transition state 5-Ring TS with syn-relationship of H and X

Regioselectivity and stereoselectivity In acyclic compounds, the configuration of tertiary amine oxide determines the stereochemistry of the alkene In cyclic compounds, ring conformation is very important

Application 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 E. 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 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

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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Sulfoxide Introduction Readily obtained by oxidation of sulfides (mCPBA or NaIO4) Sulfoxides with a -hydrogen atom readily undergo syn-elimination on pyrolysis Take place with a high syn-stereoselectivity Another useful method for making C=C bonds

Transition state 5-Ring TS with syn-relationship of H and X

Application 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

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Selenoxide Preparation of selenide Prepared by a number of different methods 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 Preparation of selenoxide Readily obtained from the corresponding selenides by oxidation

Reaction Even better methods than that of sulfoxide Elimination 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

Transition state 5-Ring TS with syn-relationship of H and X

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

In cyclic compounds, ring conformation is very important

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

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 Selenide (and sulfide) stabilize an -carbanion 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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-Hydroxy selenide

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

Reaction 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 Proceeds under the action of MsCl, SOCl2, or other appropriate activating conditions

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

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