Synthese makrocyclischer Ketone durch Ringerweiterung; ein neuer Weg zu(±)-Muscon

Synthesis of Macrocyclic Ketones by Ring-Enlargement Reactions; a New Path to (±)-Muscone A new synthetic route to macrocyclic ketones is described. Starting from 2-nitrocycloalkanones, the ring-enlarged compounds of the type 4 and 5 were prepared in three steps. Reduction of the NO₂ group with Bu³SnH and azobisisobutyronitrile led in moderate yields to simple β-keto-esters which were quantitatively hydrolyzed and decarboxylated to the ketones of the type 8 and 9 . The interesting fragrances Exaltone® ( 8a ) and (±)-muscone ( 9a ) were prepared in this way in overall yields of 22 and 18%, respectively.     

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.     

Photochemische Reaktionen 111. Mitteilung [1] Zur Photochemie α, β-ungesättigter γ, δ-Epoxyester I: Singulett- versus Triplettreaktivität

On triplet excitation (E)- 2 isomerizes to (Z)- 2 and reacts by cleavage of the C(γ), O-bond to isomeric δ-ketoester compounds ( 3 and 4 ) and 2,5-dihydrofuran compounds ( 5 and 19 , s. Scheme 1). - On singulet excitation (E)- 2 gives mainly isomers formed by cleavage of the C(γ), C(δ)-bond ( 6–14 , s. Scheme 1). However, the products 3–5 of the triplet induced cleavage of the C(γ), O-bond are obtained in small amounts, too. The conversion of (E)- 2 to an intermediate ketonium-ylide b (s. Scheme 5) is proven by the isolation of its cyclization product 13 and of the acetals 16 and 17 , the products of solvent addition to b . - Excitation (λ = 254 nm) of the enol ether (E/Z)- 6 yields the isomeric α, β-unsaturated ε-ketoesters (E/Z)- 8 and 9 , which undergo photodeconjugation to give the isomeric γ, δ-unsaturated ε-ketoesters (E/Z)- 10 . - On treatment with BF₃O(C₂H₅)₂ (E)- 2 isomerizes by cleavage of the C(δ), O-bond to the γ-ketoester (E)- 20 (s. Scheme 2). Conversion of (Z)- 2 with FeCl₃ gives the isomeric furan compound 21 exclusively.     

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.     

Photochemische Reaktionen. 109. Mitteilung [1]. Zur Photochemie konjugierter δ-Keto-enone und β,γ,δ,ϵ-ungesättigter Ketone

Photochemistry of Conjugated δ-Keto-enones and β,γ,δ,?-Unsaturated Ketones On ¹π,π*-excitation the δ-keto-enones 5–8 are isomerized to compounds B ( 18 , 22 , 26 , 28 ) via 1,3-acyl shift and to compounds C ( 19 , 23 , 27 , 29 ) via 1,2-acyl shift, whereas the β,γ,δ,?-unsaturated ketone 9 gives the isomers 32 and 33 by 1,2-and 1,5-acyl shift, respectively. Furthermore, isomerization of 6 to 24 , dimerization of 8 to 30 and addition of methanol to 8 ( 8 → 31 ) is observed. Unlike 7 and 8 the acyclic ketones 5 , 6 and 9 undergo photodecarbonylation on ¹π,π*-excitation ( 5 → 20 , 21 ; 6 → 20 , 25 ; (E)- 9 → 35–38 ). Evidence is given, that the conversion to B as well as the photodecarbonylation of 5,6 and 9 arise from an excited singulet state, but the conversion to C as well as the dimerization of 8 from the T₁-state.