Eliminative Ring Fission Research Articles

Nitrile Anion Cyclization with Epoxysilanes Followed by Brook Rearrangement/Ring-Opening of Cyclopropane Nitriles/Alkylation

[reactions: see text] The reaction of delta-silyl-gamma,delta-epoxypentanenitrile derivatives 9-12 with a base and an alkylating agent affords (Z)-delta-siloxy-gamma,delta-unsaturated pentanenitrile derivatives via a tandem process that involves the formation of a cyclopropane derivative by epoxy nitrile cyclization followed by Brook rearrangement and an anion-induced cleavage of the cyclopropane ring. Exclusive formation of a (Z)-derivative from trans-epoxides is explained by the reaction pathway that involves a backside displacement of the epoxide by the alpha-nitrile carbanion and the O-Si bond formation followed by concerted processes involving Brook rearrangement and the anti-mode of eliminative ring fission of the cyclopropane from the rotamer 19. The fact that (E)-isomers are exclusively obtained from cis-epoxides and alpha-cyclopropyl-alpha-silylcarbinol derivative 26 provides experimental support for the proposed pathway.

Dihyro- and tetrahydrofuran building blocks from 1,4:3,6-dianhydromannitol. 1. Synthesis of (1S,5R,7R)-endo-(-)- and (1S,5R,7S)-(-)-exo-brevicomin and (R)-(+)-dodecanolide

The eliminative ring fission of iodides derived from 1,4:3,6-dianhydromannitol 3 has been exploited for preparing three enantiomerically pure species, 1-3, which feature a di- or tetrahydrofuran moiety and one or two stereogenic centers. These species are extremely versatile building blocks for the construction of natural products. Their potential was demonstrated by the synthesis of the title insect pheromones

Ring‐opening reactions. 6. eliminative ring fission of aziridinium and azetidinium ions

AbstractThe reactivity ratio between the three‐ and four‐membered cyclic ammonium ions in ring‐opening elimination reactions was measured. The comparison with the analogous ratio obtained in a previous study on ring‐opening substitution reactions suggests a substantial difference in the effect of the stereochemical factors governing the two ring‐opening reactions and confirms the anomalous behaviour of small rings in the ring‐opening substitution reaction.

Reactivity of α,β-unsaturated acetals with electrophiles in the presence of organolithium–potassium reagents

2-Propenyl- and 2-(2-methylpropenyl)-1,3-dioxane react with 2 equiv. of sec-butyllithium complexed with potassium tert-butoxide in tetrahydrofuran (THF) at –95 °C undergoing a 1,4 eliminative ring fission with subsequent proton abstraction at the α vinyl site of the enol ethers produced; carbanions obtained undergo substitution and addition reactions with electrophiles.

Arenhydride, 8. Konkurrenz zwischen SET und nucleophilem Angriff bei Reaktionen von α‐Bromisobutyrophenon mit Carbanionen. Fragmentierung des Anions von Tetrahydrobianthracen

Arene Hydrides, 8. ‐ SET vs. Nucleophilic Attack in Reactions of α‐Bromoisobutyrophenone with Carbanions. Fragmentation of the Anion of TetrahydrobianthraceneSET is the main reaction pathway between α‐bromoisobutyrophenone (1) and the carbanions 7a–j− of diarylmethanes or disubstituted acetonitriles: 7− → 7. + e and e + 1 →→ Br− PhCOCMe.2 (3). Main secondary reactions are dimerization of the radical 7. (to form 6) and further reduction of 3: 7− + 3 → 7. + 4 [enolate of isobutyrophenone (5)]. Occasionally substitution products (9) of 1 are obtained. They are probably formed by combination of 7. with 3 (0% 9e at room temperature, 38% 9e at −65°C). This combination seems to be favored by cation coordination. In the reaction with 7f− (“anthracene hydride”) the dimer 6f (and probably 9f, too) undergoes fragmentation to form anthracene. The epoxide 16, arising from 1 by carbonyl attack, has been found only once with 7a–j−; (1% 16b). In contrast, 16 was the (elusive) main product in the reaction of 1 with the carbanions 7k–n− of monosubstituted acetonitriles. Here, 6 and 9 have been found only once (61, 9n). The elusive 16k–n underwent eliminative ring fission.

An Ab initio theoretical study of the eliminative ring fission in cyclopropylmethanide and cyclobutylmethanide

Ab initio computations of the eliminative ring fission of cyclobutylmethanide and cyclopropylmethanide have been performed by completely optimizing the stable geometrical structures of the cyclic and open-chain minima as well as the transition structures for ring opening. These results show that the transition state for the four-membered ring opening occurs later (in a geometrical sense) along the reaction path than for the three-membered ring opening, and that the difference in activation energy is negligibly small. The strain energy of cyclobutylmethanide is nearly equal to cyclopropylmethanide, but is released more gradually during the opening of the four-membered ring. The acceleration of ring fission due to ring strain is substantial and of comparable magnitude in the two ring openings, corresponding to a release of about three fourths of the initial strain energy in the transition states.

Eliminative ring fission of 1,2,4-trioxan-5-ones. A new approach to α-keto acids

6-Mono-R-substituted 1,2,4-trioxan-5-ones readily undergo base-catalysed O–O bond cleavage to furnish α-keto acids (RCOCOOH) in high yields even when the R-substituents are bulky.

Ring fission of cycloalkanols: the different involvement of strain in the reactivity of 3- and 4-membered rings

Rates of eliminative ring fission of cyclopropanols under basic condition are 105 to 109 faster then those of the related cyclobutanols; neither excess enthalpies of the systems nor classical ideas on strain distribution in small rings account for these ratios.

Computational analysis of the nucleophilic eliminative ring fission of bridgehead substituted 1,3-bishomocubyl acetates

Molecular mechanics (MM2) calculations on the conceivable seco-cage structures by homoketonization of two types of bridgehead substituted 1,3-bishomocubyl acetates, viz. type A : 4-acetoxy-pentacyclo[5.3.0.0 2,5.0 3,9.0 4,8] decan-6-one and its ethylene ketal, and type B: 8-acetoxypentacyclo [5.3.0.0 2,5.0 3,9.0 4,8]decan-6-one, its ethylene ketal and 8-acetoxypentacyclo[5.3.0.0 2,5.0 3,9.0 4,8]decane were performed.

Lithiation ? to heteroatoms: eliminative ring fission of heterocycles

The behaviour of some heterocycles, having two heteroatoms in a 1,4-relationship, towards lithium di-isopropylamide (LDA) has been examined. The dihydrobenzothiazines (2a–c) and (3b), morpholine (12), benzoxazine (14), oxathiane (16), piperazine (18), tetrahydroquinoxaline (20), 1,4-dithiane (25), and dihydrodioxine (27) undergo ready ‘eliminative ring fission.’ Very marked differences have been observed for unsubstituted and substituted derivatives. Whereas the dibenzoyltetrahydroquinoxaline (20) and the dioxine (27) readily react to give ring-opened products (21) and (30) respectively, substituted derivatives (22), (23), and (32) were found to be completely unreactive.

Some quantitative effects of strain on reactivity

Abstract

Polyfunctionalized hexahydro-1 (2H)-pentalenones by rearrangement of bicyclic 1,2-oxazine N-oxide derivatives

The title heterocycles rearrange into a mixture of diastereoisomeric hexahydro-1(2H)-pentalenone derivatives, which undergo nucleophilic eliminative ring fission by methanol to give 1-amino-2-nitroalkylated cyclopentancarboxylic esters. The X-ray structure determination of hexahydro-2-methyl-2-nitro-3-phenyl-6a- (1-piperidinyl) -1 (2H)-pentalenone – (2α, 3α, 3aα, 6aα) is also reported.

ChemInform Abstract: ELIMINATIVE RING FISSION OF CYCLOBUTANES: EVALUATION OF ACCELERATION BY STRAIN AND THE COMPARISON WITH CYCLOPROPANES

AbstractDie Ringspaltungsgeschwindigkeiten von (I) und (II) werden 13C‐ und 1H‐NMR‐spektroskopisch untersucht und miteinander verglichen.

Eliminative ring fission of cyclobutanes: evaluation of acceleration by strain and the comparison with cyclopropanes

Cyclobutanes, by comparison with cyclopropanes, are reluctant to undergo eliminative ring fission; the very similar strain energies are released differently in the transition states for fission.

Reactions of nitrogen containing aromatic anions with chlorocarbene

It is shown that the 4-azapentalene anion (1) and the dipyrrolo[1,2c:2',1'e]imidazolyl anion ( 2) (Li salts) undergo eliminative ring fission upon reaction with chlorocarbene in tetrahydrofuran. Acetylenes ( 12 and 18) are the result. The reaction of 1 is accompanied by ring enlargement to indolizine ( 7). When the reaction of 1 with chlorocarbene is performed in diethylether, again 7 is produced, this time accompanied by a tetracyclic valence isomer, the pyrroloazabenzvalene ( 8). Mechanistic implications, based on the finding that the site of label incorporation in the enlarged products is solvent dependent, are discussed and compared with the corresponding reactions of carboaromatic anions. Use of intramolecular oxidative coupling for the synthesis of new pyrrolo annellated heterocyclic systems is made throughout this work.

ChemInform Abstract: AMINO STEROIDS ‐ FURTHER STUDIES WITH CONANINE AND HETEROCONANINE SYSTEMS

AbstractFurther Studies with Coanine and Heteroconanine Systems.

Amino Steroids ‐ Further Studies with Conanine and Heteroconanine Systems

AbstractTreatment of any of the three following products, heteroconanol methiodide (3′), conanol methiodide (4′) or 18‐dimethylamino‐5α‐pregn‐20‐en‐3β‐ol (1), with a large excess of potassium hydroxide in hot ethylene glycol affords rapidly a mixture of heteroconanol (3, <56%>), conanol (4, <33%>) and the Δ 17(20) isomer of 1 (2,<11%>). The presence of such an isomer has not yet been reported in analogous reactions of related compounds. The Hofmann elimination product 1 is thought to be involved as an equilibrium intermediate in each of the three reactions; its isomer 2 should be formed by base‐catalyzed isomerization and not by eliminative ring fission.

Eliminative ring fission. The retro-Thorpe–Ingold effect

In eliminative ring fission of cyclopropanes by the (E1cB)Rmechanism, gem-dimehtyl substitution substantially raises ΔH‡; for oxirans, which react by the E2 mechanism, this retro-Thorpe–Ingold effect is insufficient to make ring cleavage rate-determining.

Eliminative cleavage of cyclopropanes: leaving group stabilising and transition-state structure

In eliminative ring fission of cyclopropanes, the extent of ring fission in the transition state is sensitive to the function stabilizing the leaving group; it is small when the stabilizing group is phenylsuphonyl, but substantial when it is cyano.

The contribution of ring strain to nucleofugality: the first measurement

Comparison of eliminative ring fission in a cyclopropane and elimination in an acyclic analogue allows determination of acceleration of elimination by ring strain; a factor of a least 1011.7 has been found, the largest for any heterolytic reaction.