Notiz über einen Zugang zu β, γ-ungesättigten Carbonsäurederivaten mit Hilfe der Amidacetal-Claisenumlagerung. Über synthetische methoden, 17. Mitteilung

Note on a preparation of β, γ-unsaturated carboxylic acid derivatives using the amide acetal Claisen rearrangement 3-(Trimethylsilyl)allyl alcohols smoothly undergo the amide acetal Claisen rearrangement furnishing allyl silanes. Subsequent protolysis with HF at ?20° provides a convenient, stereoselective method for the preparation of β, γ-unsaturated carboxylic acid derivatives. Three model examples illustrate the procedure.     

Thermische Lactonisierung von Estern γ-Brom-α, β-ungesättigter Carbonsäuren zu Δα-Butenoliden. Direkte γ-Bromierung von α, β-ungesättigten Säuren

By heating with iron powder at 120–150° some γ-bromo-α, β-unsaturated carboxylic methyl esters, and, less smothly, the corresponding acids, were lactonized to Δ^7alpha;-butenolides with elimination of methyl bromide. The following conversions have thus been made: methyl γ-bromocrotonate ( 1c ) and the corresponding acid ( 1d ) to Δ^α-butenolide ( 8a ), methyl γ-bromotiglate ( 3c ) and the corresponding acid ( 3d ) to α-methyl-Δ^α-butenolide ( 8b ), a mixture of methyl trans- and cis-γ-bromosenecioate ( 7c and 7e ) and a mixture of the corresponding acids ( 7d and 7f ) to β-methyl-Δ^α-butenolide ( 8c ). The procedure did not work with methyl trans-γ-bromo-Δ^α-pentenoate ( 5c ) nor with its acid ( 5d ). Most of the γ-bromo-α, β-unsaturated carboxylic esters ( 1c, 7c, 7e and 5c ) are available by direct N-bromosuccinimide bromination of the α, β-unsaturated esters 1a, 7a and 5a ; methyl γ-bromotiglate ( 3c ) is obtained from both methyl tiglate ( 3a ) and methyl angelate ( 4a ), but has to be separated from a structural isomer. The γ-bromo-α, β-unsaturated esters are shown by NMR. to have the indicated configurations which are independent of the configuration of the α, β-unsaturated esters used; the bromination always leads to the more stable configuration, usually the one with the bromine-carrying carbon anti to the carboxylic ester group; an exception is methyl γ-bromo-senecioate, for which the two isomers (cis, 7e , and trans, 7d ) have about the same stability. The N-bromosuccinimide bromination of the α,β-unsaturated carboxylic acids 1b , 3b , 4b , 5b and 7b is shown to give results entirely analogous to those with the corresponding esters. In this way γ-bromocrotonic acid ( 1 d ), γ-bromotiglic acid ( 3 d ), trans- and cis-γ-bromosenecioic acid ( 7d and 7f ) as well as trans-γ-bromo-Δ^α-pentenoic acid ( 5d ) have been prepared. Iron powder seems to catalyze the lactonization by facilitating both the elimination of methyl bromide (or, less smoothly, hydrogen bromide) and the rotation about the double bond. α-Methyl-Δ^α-butenolide ( 8b ) was converted to 1-benzyl-( 9a ), 1-cyclohexyl-( 9b ), and 1-(4′-picoly1)-3-methyl-Δ^α-pyrrolin-2-one ( 9 c ) by heating at 180° with benzylamine, cyclohexylamine, and 4-picolylamine. The butenolide 8b showed cytostatic and even cytocidal activity; in preliminary tests, no carcinogenicity was observed. Both 8b and 9c exhibited little toxicity.     

Eine einfache und flexible Synthese von Pyrrolen aus α,β-ungesättigten Sulfonen

A Simple and Flexible Synthesis of Pyrroles from α , β -Unsaturated Sulfones: The addition of alkyl isocyanoacetates and isocyanoacetonitrile to α,β-unsaturated sulfones affords a convenient and broad access to pyrroles with unusual substitution patterns (see Scheme 2). The α,β-unsaturated sulfones required as starting materials are easily obtained from different olefines.     

Photochemie von tricyclischen β, γ-γ′, δ′-ungesättigten Ketonen. 50. Mitteilung über Photoreaktionen

Photochemistry of tricyclic β, γ-γ′, δ′-unsaturated ketones The easily available tricyclic ketone 1 (cf. Scheme 1) with a homotwistane skeleton yielded upon direct irradiation the cyclobutanone derivative 3 by a 1,3-acyl shift. Further irradiation converted 3 into the tricyclic hydrocarbon 4 . However, acetone sensitized irradiation of 1 gave the tetracyclic ketone 5 by an oxa-di-π-methane rearrangement. Again with acetone as a sensitizer the ketone 5 was quantitatively converted to the pentacyclic ketone 6 . The conversion 5 → 6 represents a novel photochemical 1,4-acyl shift. The possible mechanisms are discussed (see Scheme 7). The tricyclic ketone 2 underwent similar types of photoreactions as 1 (Scheme 2). Unlike 5 the tetracyclic ketone 9 did not undergo a photochemical 1,4-acyl shift. The epoxides 10 and 14 derived from the ketones 1 and 2 , respectively, underwent a 1,3-acyl shift upon irradiation followed by decarbonylation, and the oxa-di-π-methane rearrangement (Schemes 3 and 4). The diketone 18 derived from 1 behaved in the same way (Scheme 5). The tetracyclic diketone 21 cyclized very easily to the internal aldol product 22 under the influence of traces of base (Scheme 5). Upon irradiation the γ, δ-unsaturated ketone 24 underwent only the Norrish type I cleavage to yield the aldehyde 25 (Scheme 6).     

Synthesen von 2-Pyronen aus α, β-ungesättigten Säurechloriden und tertiären Aminen

A new synthesis of 2-pyrones has been developed. Two molecules of α, β-unsaturated acid chlorides ( 8 , 12 and 18 ) condense, with loss of two molecules hydrogen chloride, to pairs of substituted 2-pyrones ( 9 and 10 , 13 and 14 , 19 and 20 ) when treated with triethyl amine in chloroform or methylene chloride at room temperature. In the case of 18 , two additional products were obtained, namely the resorcinol derivative 21 and traces of the 1, 3-cyclobutanedione derivative 22 . Under the same conditions the α, β-unsaturated acid chlorides 8 , 15 , 18 and 41 were condensed with trichloroacetyl chloride to give 6-trichloromethyl-2-pyrones ( 42 , 43 , 44 and 46 ). These 2-pyrones are valuable intermediates for the synthesis of 6-carboxy-2-pyrones and 6-methyl-2-pyrones. A methyl group in β-position of the α, β-unsaturated acid chloride appears to be essential for the described condensations, for the acid chlorides 16 and 17 did not yield defined products and the acid chloride 40 reacted with trichloroacetyl chloride in a very low yield. It is considered that the described reactions proceed via the 1, 4-addition of an acid chloride to a vinyl ketene or through the acylation of an intermediate anion by an acyl derivative as outlined in reaction scheme 1. The structures of the 2-pyrones were confirmed by their spectroscopic properties, summarized in table 3, and by some of their chemical transformations.     

Gerüstumlagerung eines α,β -ungesättigten γ,δ-Epoxiketons bei der Birch-Reduktion: Strukturaufklärung mittels 13C-INADEQUATE-NMR-Spektroskopie

Skeleton Rearrangement of an α-β-Unsaturated γ,δ-Epoxyketone during Birch Reduction: Structure Elucidation by Means of ¹³C-INADEQUATE-NMR Spectroscopy When the γ-epoxide 2 of β-ionone is treated under standard Birch-reduction conditions, unexpectedly a 70% combined yield of regioisomeric octalones 4 and 5 is isolated. These products unquestionably result form cleavage of the central epoxide C?C bond. The structure of compounds 4 and 5 could be determined by means of ¹³C-INADEQUATE-NMR spectroscopy.     

Über die Reaktion von tertiären Vinylcarbinolen mit Isopropenyläther Eine neue Methode zur Herstellung von γ, δ-ungesättigten Ketonen

A novel acid-catalysed reaction of isopropenyl ether with tertiary vinyl carbinols giving γ, δ-unsaturated ketones in high yields is described. Methylheptenone, geranylacetone, farnesylacetone and analogous ketones were prepared by this convenient and efficient new method, which involves a Claisen-rearrangement step.     

Über die Reaktion von tertiären Vinylcarbinolen mit Vinyläthern Eine neue Methode Zur Herstellung von γ,δ-ungesättigten Aldehyden

A novel acid catalysed reaction of vinyl ethers with tertiary vinyl carbinols giving γ, δ-unsaturated aliphatic and alicyclic aldehydes in high yields is described. This new procedure for the utilization of the Claisen rearrangement reaction provides a convenient and efficient route to such aldehydes.