Mesomeric Vinyl Cations. Part II. Solvolysis of 2-bromo-1, 3-butadienes

In contrast to 2-bromo-1, 3-butadiene ( 5 ), the di-, tri- and tetramethyl derivatives 6 – 11 show remarkable solvolytic reactivity. First order rate constants and products of these bromodienes in 80% ethanol have been determined. Rates are very sensitive to the ionising power of the solvent but are not affected by triethylamine. Three types of products are formed, i.e. alkenynes, α,β-unsaturated ketones and 4-ethoxyallenes. One methyl group on C-4 of 5 increases the reaction rate by a factor of ca. 10²; two methyl groups increase the rate by ca. 10⁴. Methyl substituents at C-1 have only a slight influence, apparently as a result of a rate-decreasing polar effect and a compensating rate-increasing steric effect. The results of this study are consistent with a unimolecular ionization mechanism involving a mesomeric vinyl cation 12a ? 12b as an intermediate.     

Vinyl polymerization versus [1,3] O to C rearrangement in the ruthenium-catalyzed reactions of vinyl ethers with hydrosilanes

Two reactions, vinyl polymerization and [1,3] O to C rearrangement of vinyl ethers, are investigated in the ruthenium-catalyzed reaction with hydrosilanes. The reaction pathways are dependent on the substituents of the vinyl ether, in particular, those of the alkoxy group. Primary-, secondary-, and tertiary-alkyl vinyl ethers, ROCHCH₂, are polymerized with ease to give the corresponding polymer in good yields. When R is electron-donating benzyl groups, the reaction does not give the polyvinyl ether but results in [1,3] O to C rearrangement to give the corresponding aldehyde, RCH₂CHO in moderate to good yields. The rearrangement selectively proceeds when vinyl ethers having α-substituents are used as the starting materials to give the corresponding ketones in high yields. With catalytic amounts of hydrosilanes, the rearrangement gives ketones or aldehydes selectively. In sharp contrast, use of excess amounts of hydrosilanes leads to the rearrangement followed by reduction of the formed carbonyl group to give the corresponding silyl ethers in good yields. Nature of catalytically active species is discussed.     

Unsaturated carboxylic acid dienolates. Michael addition to enones through tandem 1,2-addition - oxy-cope rearrangement.

Michael addition of the dienolate derived from 2-butenoic acid to 1,3-diphenylpro-penone occurs through a 1,2-addition followed by a ³,3-sigmatropic rearrangement. α,γ -re-gioselectivity found for Michael addition to other styryl ketones depends on the steric parameter of the substituents at the carbonyl group, in agreement with the same tandem addition rearrangement mechanism.     

β-Cleavage of Bis(homoallylic) Potassium Alkoxides. Two-Step Preparation of Propenyl Ketones from Carboxylic Esters. Synthesis of ar-Turmerone, α-Damascone, β-Damascone,and β-Damascenone

The transformation of 36 bis(homoallylic) alcohols VII to alkenones IX and X via β-cleavage of their potassium alkoxides VIIa in HMPA has been investigated (cf. Scheme 2). These studies have established an order of β-cleavage for 2-propenyl, 1-methyl-2propenyl, 2-methyl-2-propenyl, 1,1-dimethyl-2propenyl, and benzyl groups in alkoxides 49a – 56a and have allowed a comparison between the β-cleavege reaction and the oxy-Cope rearrangement in alkoxides 74a – 83a . As illustrative syntheti applications, a two-step preparatio of propenyl ketones 15 – 42 from carboxylic esters is described, together with syntheses of ar-turmerone ( 48 ), α-damascone ((E)- 71 ), β-damascone ((E)- 109 ), and β-damascenone ((E)- 111 ).     

Beitrag zur massenspektrometrischen retro-Diels-Alder-Reaktion: 1,2,3,4-Tetrahydrophenanthren. 35. Mitteilung über massenspektrometrische Untersuchungen

Contribution to the Mass Spectral retro-Diels-Alder Reaction: 1,2,3,4-Tetrahydrophenanthrene [1,4-¹³C]-1,2,3,4-Tetrahydrophenanthrene (1) was synthesized starting from [1,4-¹³C]-succinic acid. The mass spectral behavior (EI./MS., 70eV) of 1 is very similar to that of tetraline [2] concerning its loss of ethylene from the molecular ion. Similarly the fragmentation reaction of the synthetic precursors, ketones 7 and 8 , seems to partly undergo a carbon rearrangement reaction prior to the elimination of ethylene which is unlike to the behavior of α-tetralone.     

Photochemische Reaktionen. 52. Mitteilung [1]. Zur Photochemie von α,β-ungesättigten cyclischen Ketonen: Spezifische Reaktionen der n,π*- und π,π*-Triplettzustände von O-Acetyl-testosteron und 10-Methyl-Δ1,9-octalon-(2)

The photochemistry of the conjugated cyclohexenones O-acetyl testosterone ( 1 ) and 10-methyl-Δ^1,9-octalone-(2) ( 24 ) has been investigated in detail. The choice of reaction paths of both ketones depends strongly on the solvent used. In t-butanol, a photostationary equilibrium 1 ? 3 is reached which is depleted solely by the parallel rearrangement 1 → 5 (Chart 1; for earlier results on these reactions see [2a] [6] [7]). In benzene, double bond shift 1 → 16 (Chart 3) occurs instead, which is due to hydrogen abstraction from a ground-state ketone by the oxygen of an excited ketone as the primary photochemical process. In toluene, the major reaction is solvent incorporation ( 1 → 17 , Chart 4) through hydrogen addition to the β-carbon of the enone, accompanied by double bond shift and formation of saturated dihydroketone as the minor reactions. Contrary in part to an earlier report [19], the photochemical transformation of the bicyclic enoné 24 exhibit a similar solvent dependence. The corresponding products 25 – 29 are summarized in Chart 5 and Table 1. Sensitization and quenching experiments established the triplet nature of the above reactions of 1 and 24 . Based on STERN -VOLMER analyses of the quenching data (cf. Figures 2, 4–8, and Table 3), rearrangement, double bond reduction and toluene addition are attributed to one triplet state of the enones which is assigned tentatively as ³(π, π*) state, and the double bond shift is attributed to another triplet assigned as ³(n, π*) state (cf. Figure 9). The stereospecific rearrangement of the 1α-deuterated ketone 2 to the 4β-deuterio isomer 4 shows the reaction to proceed with retention at C-1 and inversion at C-10. The 4-substituted testosterone derivatives 33 – 36 (Chart 8) were found to be much less reactive in general than 1 . In particular, 4-methyl ketone 33 remains essentially unchanged on irradiation in t-butanol, benzene and toluene.     

Collision-induced dissociation study of cyclization of α-diazo-ω-arylsulphonylaminoalkan-2-ones

The collision-induced dissociation mass-analysed ion kinetic energy (CID MIKE) spectra (electron impact and chemical ionization) of five α-diazo-ω-arylsulphonylaminoalkan-2-ones and corresponding N-arylsulphonylazetidin-3-ones and N-arylsulphonylpyrrolidin-3-ones were studied. The [M ? N₂]⁺˙ and [MH ? N₂]⁺ ions of two types of the diazo ketones provide CID MIKE spectra similar to those of the corresponding M⁺˙ and MH⁺ of the heterocyclic compounds, i.e. a cyclization analogous to that in solution takes place. For the other three types of diazo compounds the Wolff rearrangement prevails in both the gas and liquid phases. The effect of the substituents on the cyclization process was studied. The data obtained permit the results of acid-catalysed cyclization of similar diazo ketones to be predicted on the basis of their CID MIKE spectra. Chemical ionization provides a closer similarity with reactions in solution than electron impact ionization, which can be rationalized by the protonation of the diazo ketone molecule being the driving force of the cyclization reaction either in solution or in the ion source of a mass spectrometer.     

Synthesis of Tricyclic Ketones with Sesquiterpene Skeletons by Acid-Catalyzed Rearrangement of β-Monocyclofarnesol

Starting from dihydro-β-ionone ( 6 ) a mixture of three tricyclic ketones with sesquiterpene skeletons 14 , 15 , and 16 was prepared by Wittig-Horner reaction with triethyl phosphonoacetate, Red-Al^® reduction, acid-catalyzed rearrangement of the resulting β-monocyclofarnesol ( 7 ), alkaline hydrolysis of the formates 8 – 10 , and subsequent molybdenium-catalyzed oxidation. The mechanistic background of the acid-catalyzed rearrangement of β-monocyclofarnesol ( 7 ) is discussed in detail. The resulting tricyclic ketones 14 – 16 exhibit intense woody odor notes with peppery vetiver or camphoraceous cedarwood aspects.     

Addition von Aldehyden an aktivierte Doppelbindungen,XXXIV1). Addition von Aldehyden an cyclische α-Methylenketone

Addition of Aldehydes to Activated Double Bonds, XXXIV¹⁾. Addition of Aldehydes to Cyclic α-Methylene Ketones The thiazolium salt-catalyzed addition of aldehydes to the cyclic α-methylene ketones 3, 4, 7, 8, 48 , and 49 leads to γ-diketones 9 – 22, 50 – 53 ; some of them were converted into unsaturated ketones 23 – 28 , pyrroles 29 – 34, 37 – 43 , and furans 35, 36, 44 – 46 . The α-methylene ketones were synthesized by retro Diels-Alder reaction of the corresponding norbornene compounds 1, 2, 5, 6, 47 .     

Cyclisations with methacrylic acid in PPA. On the synthesis of cyclopenta[b]thiophenones

The reaction between some 2-substituted thiophen derivatives and methacrylic acid in PPA has been studied. Isomeric cyclopenta[b]thiophen ketones were formed in several cases, depending on the substituents. Features of their ¹³C and ¹H NMR spectra are discussed and evidence is presented for ringclosure of 3(2-thienyl) propionic acids without rearrangement, in contrast to statements in the literature.     

Diazoaldehyde Chemistry. Part 1. Transdiazotization of Acylacetaldehydes in Neutral-to-Acidic Medium. A Direct Approach to the Synthesis of α-Diazo-β-oxoaldehydes

First ever non-deformylating transdiazotization of acylacetaldehydes was achieved: the reactions of 2-azido-l-ethylpyridinium tetrafluoroborate ( 4 ) with acylacetaldehydes 3 proceeded partially without deformylation to yield 16 new α-diazo-β-oxoaldehydes 1 along with diazomethyl ketones 2 , especially in the presence of NaOAc (Scheme 1, Tables 1 and 2). The product distribution was substituent-dependent and could be correlated quantitatively. This new diazotization reaction appears as an alternative, direct, and more general method for the synthesis of these diazooxoaldehydes. α-Oxocycloalkanecarbaldehydes 5 gave only traces (if any) of α-diazocycloalkanones 7 , and rearrangement products 6 were isolated (Scheme 2). Mechanisms of the reactions are discussed (Schemes 4 and 5).     

The Reaction of Phosphoryl Chlorides with Enamines - A New Approach to β-Ketophosphonates

Abstract

Several approaches are available for the preparation of β-ketophosphonate esters. A Michaelis-Arbuzov approach using the reaction of an α-halo ketone with a trialkyl phosphite may in certain instances be controlled to favor the preparation of the target materials. However, an alternative pathway leading to the formation of vinyl phosphate esters often predominates. (This reaction system has recently been reviewed by Borowitz and Borowitz.¹) An alternative approach is that developed in recent years by Wiemer, et al.² involving the rearrangement of vinyl phosphate esters to the β-ketophosphonates.     

Photo-CIDNP. Investigation of β,γ-Unsaturated Ketones: Evidence for Temperature-dependent S1 vs. T2 Reactivities of Cyclopent-2-enyl Methyl Ketones

On ultraviolet irradiation of the cyclopent-2-enyl methyl ketones 1a – c at ?54° ? t ? 139°, photo-CIDNP. effects of the starting ketones, the 1,3-acetyl shifted isomers (2) , and radical disproportionation and combination products (4 – 7) were observed. These effects show a unique dependence of the polarization phase on temperature which is a novel feature in photo-CIDNP. studies. The results of the investigation, which also included experiments using triplet quenchers, triplet sensitizers and radical scavengers, are rationalized in terms of Schemes 2 and 3. α-Cleavage is a major excited-state reaction of 1a – c on direct irradiation. Temperature-activated α-cleavage (k(t)) to the radical pair R · · R ′¹ and intersystem crossing (k_isc) to the T₂ state are among the competing S₁ deactivation processes. The T₂ state in turn cleaves (k) to R · · R ′³ A ‘low-temperature range’ with k_isc ? k(t) and a ‘high-temperature range’ with k(t) ? k_isc exhibiting preferential reactivity from the T₂ and S₁ states, respectively, can be defined for all three β,γ-unsaturated ketones 1a – c .     

d5-Reactions of Doubly Deprotonated γ,δ-Unsaturated Carbonyl Derivatives with Electrophiles. A Novel Approach to the Synthesis of Tetrahydrofuran and Tetrahydropyran Derivatives

The dienone-dianion derivatives 1 react with all types of electrophiles tested (alkyl halide, silyl chloride, ester, ketone, aldehyde, epoxide) to give β, γ-unsaturated carbonyl compounds of type A (see Formulae 2 – 6 , 13 , 14 and Tables 1–5). The α- and β-hydroxyalkylation products obtained from 1a – 1d can be converted to tetra-hydrofuran and tetrahydropyran derivatives 7 and 16 , respectively (Tables 1 and 2), those from the sulfur analogues 1e and 1f to ketene thioacetals 9 and to dienone derivatives 10 and 12. The t-butyl and α-hydroxy-ketones are cleaved to give nitriles, amides, carboxylic acids and esters (Formulae 16 - 25 ). The reagents 1 allow to synthesize products with distant functional groups in one step (cf. 1,8-diketones 14 and Formulae 26 – 30 ); they correspond to the d⁵-synthons 31 – 33 ; in Table 6, they are compared with other d⁵-reagents.     

Reaction of Aziridinones with 2-Lithio-1, 3-Dithiane: Selective Cleavage of the Aziridinone Ring

The reaction of aziridinones (1a-1d) with tert-butyllithium at room temperature affords α-hydroxy imines (5ax-5dx).¹ One possible pathway leading to these products involves the formation of 2 as an intermediate, followed by rearrangement to 3. In fact, under carefully controlled conditions that prevent the rearrange-of 2 to 3, α-amino ketones (4ax-4dx), which arise from the protonation of 2, can be isolated. Other α-amino ketones were synthesized in a like manner from aziridinones by treatment with a variety of alkyllithium reagents.² Baumgarten and co-workers³ subsequently reported similar products from the reaction of phenyllithium and methyllithium with an aziridinone. In an attempt to extend this study to other organolithium reagents, especially those bearing functional groups, we have investigated the reaction of     

Semicorrin Metal Complexes as Enantioselective Catalysts. Part 1. Synthesis of chiral semicorrin ligands and general concepts

An efficient synthesis of chiral semicorrin ligands is described (see 6 – 9 , Schemes 2 and 3). Both enantiomers are readily obtained in enantiomerically pure form starting either from D -or L -pyroglutamic acid ( 1 ). Semicorrins of this type possess several features that make them attractive ligands for enantioselective control of metal-catalyzed reactions. Their structure is characterized by C₂ symmetry, a conformationally rigid ligand system, and two stereogenic centers adjacent to the coordination sphere. In a metal complex, the two substituents at the stereogenic centers shield the metal atom from two opposite directions and, therefore, are expected to have a pronounced effect on the stereochemical course of a reaction occurring in the coordination sphere. The structure of these two substituents can be easily modified in a variety of ways. A series of (semicorrinato)copper(II) complexes (see 10 – 14 , Scheme 4) has been prepared, and in one case ( 14 ), the three-dimensional structure has been determined by X-ray analysis (Fig. 1).     

An Unusual Domino Retro‐Ene–Conia Reaction: Regio‐ and Stereoselective One‐Carbon Ring Expansion of Fenchol Derivatives

The 2-exo-substituted fenchol derivatives 1 – 7 , easily prepared from (−)-fenchone in good-to-excellent yields, were pyrolyzed by dynamic gas-phase thermo-isomerization (DGPTI). At temperatures of ca. 620°, the substrates with a hydroxyallyl ( 1 – 4 ) or a hydroxypropargyl moiety ( 6 ) underwent an initial retro-ene reaction under cleavage of the C(2) C(3) bond to form enol-ene intermediates with no loss of optical activity. These intermediates then experience either tautomerization to the corresponding α,β-unsaturated ketones or subsequent Conia rearrangement under one-carbon ring expansion of the fenchone system to a bicyclo[3.2.1]octane framework. In the case of the isopropenyl substrate 3 , the sterically crowded Conia product underwent a new type of ‘deethanation’ reaction by stepwise loss of two Me radicals, giving rise to the thermodynamically favored enone 21 . A similar relaxation behavior was observed in the case of the ethynyl substrate 6 , which showed a remarkable 1,3-Me shift after the Conia reaction, leading to the α,β-unsaturated cyclic ketone 25 . The homolytic cleavage of the weakest single bond in 1 – 3 turned out to be a competing reaction pathway. Intramolecular H-abstraction within the generated diradical intermediates produced the monocyclic ketones 8, 16 , and 19 , besides the products obtained by tautomerization and Conia reaction. In contrast, a Ph substituent at C(2) in 7 allowed only the passage through a diradical species to provide phenone 26 , which was converted by regioselective Baeyer–Villiger oxidation to the optically active cyclopentanol 29 . Both reaction channels, the domino retro-ene–Conia rearrangement and the diradical-promoted H-transfer, have been shown to proceed highly stereoselectively. The absolute configuration of the newly formed stereogenic centers in all compounds was assigned by ¹H-NOE experiments. The reaction mechanism of the novel domino retro-ene–Conia reaction was established by both a series of ²H- and ¹³C-labeling experiments, as well as by a detailed computational analysis.     

Influence of the structures of α-halo ketones and thioamides on the Hantzsch synthesis of thiazoles and thiazolo[5,4-b]indoles. A new approach to 4-acetyl-2-methyl-4H-thiazolo[5,4-b]indole

In reactions with some α-halo ketones (3-bromo-1,1,1-trifluoropropan-2-one, 1-acetyl-2-bromoindolin-3-one, and α-bromoacetophenone), thioacetamide and a series of thioamides of aromatic and heteroaromatic acids are transformed into 4-hydroxy-Δ²-thiazolines rather than into thiazoles (the expected Hantzsch reaction products). To the contrary, thiazoles are produced in the reactions of the same α-halo ketones with thioamides of phenylacetic, diphenylacetic, 3-indolylacetic, or cyanoacetic acids. The abnormal course of the Hantzsch reaction in the former case results from the fact that 4-hydroxy-Δ²-thiazolines, which are intermediates in the thiazole synthesis, undergo virtually no dehydration under the Hantzsch reaction conditions. The ease of dehydration of hydroxythiazolines under the conditions of the thiazole synthesis and the possibility of the spontaneous thiazole synthesis depend on the nature of the substituent at position 2 and, consequently, on the structure of the starting thioamide. The Me, Ar, and Het substituents impede dehydration, whereas substituents containing the α-methylene (methine) unit at the C(2) atom of the thiazoline moiety substantially facilitate this reaction. The conditions for the dehydration of 4-acetyl-2-methyl-8b-hydroxy-3a,8b-dihydro-4H-thiazolo[5,4-b]indole under basic catalysis were found, and a new procedure was developed for the preparation of thiazoles and 2-R-thiazolo[5,4-b]indoles, whose synthesis presents difficulties or is impossible under standard conditions.     

Umsetzungen von Dilithio-nitroalkanen und -allylnitroderivaten mit Carbonylverbindungen

Reactions of dilithio-nitroalkanes and dilithio-allynitroalkanes with carbonyl compounds Primary nitro compounds can by acylated via dilithium derivatives 5 with carbonic-acid derivatives to give α-nitro esters 6a – i and with carboxylic-acid esters and anhydrides to give α-nitroketones 6j – q . In the reaction of 1-nitro-1-buten with two mol-equiv. of butyllithium, the dilithium compound 10 is formed by successive Michael-addition and nitronate deprotonation. Dilithium derivatives 5 also react with ketones and benzaldehyde (→ 18a – g ); the nitro aldols 25 and 26 are likewise formed by addition of doubly deprotonated allylic nitro compounds. Some of the products have been further transformed by reduction or by Nef-reactions to the hydrochloride of the α-amino-acid 26 , to 2-amino-alcohols 28a and 28b , to α-hydroxyamino-acid esters 27a – c , to α-hydroxyimino esters 35 and 36 , to α-hydroxyimino ketones 31 and 33 , to the α-diketone 34 , and to the α-keto ester 37 .     

Studies on the reactions of silyl enol ether with perfluoroorganic compounds I. The reaction of silyl enol ether with perfluoroalkyl iodide

The reaction of silyl enol ethers ( 1a-1e ) with perfluoroalkyl iodides ( 2f–2k ) initiated with sodium dithionite was studied. α-Perfluoroalkyl ketones (3) were synthesized in excellent yield by this method. α, β-Unsaturated fluorinated ketones (4) were obtained easily by dehydrofluorination of the α-perfluoroalkyl ketones. A radical mechanism was proposed.