Alicyclic Chemistry Volume 6

A Review of the Literature Published During 1976

By M. A. McKervey

The Royal Society of Chemistry

Copyright © 1978 The Chemical Society
All rights reserved.
ISBN: 978-0-85186-632-1

Contents

Chapter 1 Three-membered Rings By B. Halton, 1,
Chapter 2 Four-membered Rings By I. Watt, 94,
Chapter 3 Five- and Six-membered Rings and Related Fused Systems By N. M. D. Brown and D. J. Cowley, 144,
Chapter 4 Medium- and Large-ring Compounds By E. J. Thomas, 180,
Chapter 5 Bridged Carbocyclics By G. B. Gill, 236,
Author Index, 358,

CHAPTER 1

Three-membered Rings

BY B. HALTON

1 Introduction, Theory, Structure, and Spectroscopy

Since the last Report the number of publications containing material relevant to this chapter has increased by over 10% to a total now approaching one thousand. There have been numerous reviews and articles incorporating aspects of carbocyclic three-membered rings.

Of the theoretical studies that have appeared, the MINDO/3 semiempirical MO treatment, developed by Dewar, has been expanded to unrestricted open-shell treatment by Bischof and applied to a series of radicals including the cyclopropyl species. A MINDO/3 study of the thermal decarbonylation of cyclopropanone by Shevlin and co-workers predicts the non-linear cheletropic mode of the reaction (ΔH* 41 kcal mol-1) to be favoured by ca. kcal mol-1 over the linear mode, in agreement with orbital symmetry concepts. An alternative approach to the assessment of destabilization (strain) energies by the use of ab initio methods provides values more closely related to the experimental values than previous work. Geometry-optimized ab initio calculations indicate that electropositive substituents such as lithium are particularly effective in stabilizing planar rather than tetrahedral arrangements at four-co-ordinated carbon; 1,1-dilithiocyclopropane and 3,3-diiithio-cyclopropene are thus predicted to be more stable in a planar than in a tetrahedral arrangement at C-1 and C-3, respectively, and the authors recommend experimental testing of their hypothesis.

Theoretical studies of the cyclopropenyl cation have continued. On the C3H3+ energy surface, energy-minimized ab initio calculations show the cyclopropenyl cation to be the most stable isomer with a stabilization energy of ca. 60 kcal mol-1; the next most stable species is the propargyl cation with an energy ca. 34 kcal mol-1 higher. The results show that the standard free energy of formation of the cyclopropenyl cation compares very favourably with the experimental value (ΔH°f calc. 253, measured 256 [+ or -] 2 kcal mol-1) and its ring-opening is predicted to have a barrier of 83 kcal mol-1. On the C4H5 energy surface, the methylcyclopropenyl cation has the lowest energy with enhanced aromatic stabilization. The homocyclopropenyl cation, however, is better depicted in terms of cyclobutenyl-like geometry rather than that corresponding to a true bicyclic arrangement. Furthermore, this latter cation is predicted to undergo degenerate circumambulatory rearrangement by a Woodward-Hoffmann-forbidden process with control taking place from the orbital subadjacent to the HOMO. The experimental vibrational frequencies of cyclopropane have been reproduced far more accurately by employing the 4-31G basis set incorporating a scale-factor to reduce the ab initio force constants. In this way the average deviation in the vibrational frequencies is 0.74%

The ionization energy of methylenecyclopropene, as yet unmeasured, is predicted to be 9.11 eV.

The electronic effects of substituents on the structure of the cyclopropane ring continue to attract attention. The X-ray structure of 1,1,2,2-tetracyanocyclopropane shows the C-1 — C-2 bond to be lengthened (1.563 Å), whereas the remote ring bonds in the cyclopropane derivatives (1), (2), (3), and (4) are shortened in accord with the Walsh orbital model. The microwave spectrum of (1) shows that the molecule adopts the bisected conformation depicted with the chlorine atom cis with respect to the C-1 proton. A bisected conformation is also observed in the dione (2) where the carbonyl groups are each cis with respect to the adjacent cyclopropane ring, but trans with respect to each other. The n.m.r. spectra of partially oriented chloro-, bromo-, and cyano-cyclopropane provide some indirect evidence in support of the orbital theory of substituent effects since the distance between protons on the same side of the ring as the substituent is substantially less than the corresponding distance on the opposite side. However, microwave data on ‘all-cis‘-1,2,3-trifluorocyclopropane and 3,3-difluorocyclopropene provide further examples of the inadequacies associated with the simple Walsh model for saturated substituents. In the former, the three equivalent ring bonds are shortened (1.507 Å) when compared with cyclopropane (1.510 Å) while the latter exhibits a lengthened double bond (1.322 Å) and shortened single bonds (1.438 Å).

Full structural details on the trisdimethylaminocyclopropenyl cation have appeared. The X-ray data recorded for 1,1-dichloro-2,5-diphenylcyclopropa-benzene, the fourth cyclopropa-arene to be subjected to structural analysis, show the 1a — 5a bridge bond to be short (1.351 Å), but not as short as that in cyclopropene (1.296 Å); no evidence for bond localization was found.

The microwave spectrum of bicyclo[2,1,0]pentane and six deuterium-labelled species has led to a complete structural analysis resulting in the parameters shown in (5) and an X-ray analysis of the 1-phenyl-exo-5-carboxylic acid derivative confirms the earlier n.m.r. assignments made by Schaffner. Gas-phase electron diffraction data on anti-tricyclo[3,1,0,0]hexane show that the four-membered ring is planar with the three-membered rings canted out of the plane by 113°.

The structure and absolute configuration of ( – )-mylitol has been shown to be that depicted by (7), with the novel 5,3,6,3 fused ring system, and not the previously proposed arrangement (6). Compound (8; R = cyclopropyl) shows a 6nm hypso-chromic shift in the u.v. spectrum when compared with (8; R = H) and X-ray data show the cyclopropane ring to adopt a perpendicular conformation with respect to the pentamethine chain. The first structural parameters of an organometallic complex containing a bicyclo[5,1,0]octyl ligand, and a bicyclo[2,2,1]heptyl system with a spiro-cyclopropane at C-7, have been reported. Each of the C-7 and C-8 epimers of 7-chloro-7-phenyl-2,5-dioxabicyclo[4,1,0]heptane and 8-phenylbicyclo[5,1,0]octa-2,4-diene-8-phosponate, respectively, have now been subjected to structural analysis. X-ray results for a number of other cyclopropane derivatives and compounds containing fused cyclopropane rings have been noted.

The crystal structure of 2,2,2′,2′-tetrachloro-3,3,3′,3′-tetramethyl-1,r-bicyclopropyl has appeared and the photoelectron spectrum of parent 1,1′-bicyclopropyl has been analysed. The present molecule shows strong conformationally dependent conjugative interaction of the Walsh orbitals of approximately the same magnitude as the interaction between the double bonds of buta-1,3-diene. However, in sterically fixed disubstituted bicyclopropyls the substituents considerably reduce this interaction. Steric potential curves for several bicyclopropyls and substituted cyclopropanes have been calculated by the empirical force field method and the total potentials obtained satisfactorily reproduced the known conformational behaviour. The photoelectron spectra of cyclopropene, methylenecyclopropane, and benzvalene have been subjected to analysis and in the latter case the geometrical distortion of the bicyclobutyl moiety has a significant impact on the electronic structure.

Chiroptical measurements in the chrysanthemic acid series have shown that 1,2,2,3-tetra-alkylcyclopropanes have the same chiralities as, yet Cotton effects opposite to, those previously reported for corresponding 1,3-dialkylcyclopropanes. Magnetic circular dichroism of cyclopropane and c.d. studies of optically active derivatives indicate that configuration interaction is of considerable importance in the low-energy excited states.

Conformational and i.r. studies of various cyclopropane derivatives have been conducted and Compton profiles obtained for cyclopropane and trimethylenecyclo-propane.

From 13C n.m.r. studies, Pomerantz and co-workers have now shown that JC-1, C-3 in the bicyclobutane (9) is negative ( – 5.4 [+ or -] 0.5 Hz); this provides the only known example of negative coupling between adjacent carbon atoms. The data obtained are in full agreement with the INDO coupled Hartree-Fock calculations of Schulman who has now calculated all the constants for bicyclobutane; thus the predictive role of hybridization has value. The bicyclobutyl radical is predicted by ab initio calculations to be an anti-W long-range coupled system.

The 13C n.m.r. spectra of the cycloalka-arenes continue to attract attention although the details of cyclopropa-arene 1H and 13C n.m.r. spectra are still not fully understood. From carbon magnetic resonance studies, the cyclopropabenzenyl cations (10) — (12) show significant charge delocalization into the fused aromatic ring, but in (11) and (12) only a small amount of charge is delocalized into the phenyl substituents. Cations (10) and (11) also exhibit the largest carbon–fluorine coupling constants yet recorded [(10), 474; (11), 461 Hz], clearly indicating a contribution from backbonding by the halogeno-substituent.

A mass spectral study of the 1,1-dihalogeno precursors of (10) and (11) and suitable deuteriated analogues has shown that complete hydrogen scrambling occurs prior to the loss of H· or X· from the molecular ion. A series of cyclopropyl ethers has been subjected to chemical ionization mass spectrometry and other routine electron-impact studies of cyclopropane-containing compounds are included for completeness. The gas-phase ion chemistry of mono substituted cyclopropanes has been examined and ion-impact energy-loss spectrometry applied to a series of cycloalkenes including cyclopropene.

The acid dissociation constants of deltic acid (2,3-dihydroxycyclopropenone) (pK1] 2.57, pK2 6.03 at 25 °C) indicate that it is a much weaker acid than its higher homologues (cf. squaric acid: pK]2ITL 0.54, pK2 3.48). The thermodynamic pKa values have been determined (in water at 25 °C) for the substituted cyclopropanes (13), (14), and (15). In general, intramolecular hydrogen-bonding in the acids (14) and (15) was found to be at a maximum in the bicyclo[2,1,0]-series (15; n = 2) and minimal in the bicyclo[1,1,0]-series (15: n – 1). This unusual and unexpected observation has been explained by invoking a strong C-1 — C-3 bond interaction with the carboxylic acid carbonyl group in (15; n = 1), resulting in stabilization of the perpendicular conformation depicted in (16).

Bomb-calorimetric and vapour-pressure measurements provide the standard free enthalpy of formation of diphenylcyclopropenone as 132 kcal mol-1. From their study the authors conclude that the strain energy is ca. 78 kcal mol-1, a value higher than that obtained for cyclopropene but comparable to those of bicyclo[1,1,0]butane and cyclopropabenzene.

A 1:1 complex formed between cyclopropane and chlorine has been subjected to study, and the application of various spectroscopic techniques to triscyclopropyl-aluminium lends support to a dimeric species in solution and in the gas phase in which the cyclopropane ring acts as a bridging ligand.

2 Synthesis of Three-membered Rings

Intramolecular Cyclization Reactions. — Apart from more routine applications, the base-catalysed 1,3-elimination route to cyclopropanes has seen a number of interesting developments during the period of this Report.

The synthesis of cyclopropanes from allyl chlorides, e.g. (17), via hydroboration is improved by the use of 9-borabicyclo[3,2,1]nonane (9-BBN) and is highly stereo-selective. The elimination step (Scheme 1) involves inversion of configuration at the carbon atom bearing the boron substituent and is in contrast to the general reactions of organoboranes. The reaction holds possibilities for optical synthesis with chiral organoboranes. The stereoselectivity observed in the cyclization of (18) to (19) and (20) is markedly influenced by the solvent employed. With sodium methoxide in THF (18; R = H) affords the trans-cyclopropane (20; R = H) exclusively, and (18; R = Ph) gives (19; R = Ph) and (20; R = Ph) in a ratio of 1:3. However, in hexa-methylphosphoramide, (18; R = H or Ph) yields (19; R = H or Ph) and (20; R = H or Ph) in a ratio of ca. 85:15. These results contrast sharply with the base-induced cyclization of 2-halogenomethyl glutarates in which these solvents have the opposite effect on the product stereochemistry.

Dicyclopropyl ketone (21) proves to be a valuable starting material for the synthesis of dispiro[2,0,2,1]heptanes as shown in Scheme 2, and the cyclopropylidene compound (23) has been used in the synthesis of various rotanes (see pp. 20 and 71). The synthesis of dimethyl bicyclo[1,1,0]butane-1,3-dicarboxylate from dimethyl 1-halogenocyclobutane-1,3-dicarboxylate is readily effected by base, but it is surprising to find that dehydrochlorination is more efficient than dehydrobromination. βγ-Epoxycarbanions have proved to be particularly useful precursors to cyclo-propylcarbinols, vinylcyclopropanes, and bicylobutanes. Thus treatment of the arenesulphone (24) with butyl-lithium gives rise to the cyclopropylcarbinol (25) in yields of 80 — 95%. Dehydration of (25) produces a vinylcyclopropane which, on epoxidation, generates a bicyclobutane precursor (26) capable of cyclization in yields of 25 — 60%. The reaction also proceeeds in high yield (>85%) with the mono-epoxide of cyclo-octa-1,5-diene and the exocyclic epoxide of 5-methylenecyclo-octene to give the corresponding bicyclo[4,1,0]heptane derivatives. Even in the acyclic case, where cyclization to the γ-position to give a cyclobutane is the sterically more favoured process, cyclopropane ring-formation occurs exclusively, and the method appears to have significant potential.

The previously reported synthesis of cyclopropane dithioacetals from ethylene oxides has been improved upon and a ‘one-pot’ procedure can now give rise to these compounds in 50 — 80% yields. Although treatment of the mesylate from a 3-hydroxy-olefin with alkaline hydrogen peroxide generally results in SN2 displacement and hydroperoxide formation, the mesylate (27) undergoes preferential cyclization.52 The stereochemistry of the 1,3-elimination reaction has been examined by employing cis– and trans-2-iodomethylcyclohexyl tosylates. The trans-isomer affords norcarane as expected and the cis-isomer gives products by way of 1,2-elimination.

The reaction of (ω-halogeno-1-(N N-dialkylamino)cycloalkenes with amines is known to result in a Favorskii-type ring contraction, giving rise to gem-diamino-bicyclo[n,1,0]alkanes, but, under the same conditions, the acyclic analogue (28) yields predominantly acyclic products. However, by employing (28), AgBF4, and Me2NH in a molar ratio of 1:1:2, cyclization is almost quantitative. Starting from methyl 3-cyanopropanoate, 1-cyano-2,2-dideuteriocyclopropane can be obtained in high yield. The dianion obtained from benzophenone anil (by reaction with alkali metal) is sufficiently basic to induce 1,3-elimination in ethyl 4-chlorobutanoate to give ethyl cyclopropanecarboxylate. The ester then suffers displacement by the base, resulting in a cyclopropanecarboxamide.

The Grignard reagent (29) derived from the ethylene acetal of 4-bromobutan-2-one, previously reported as unavailable, has now been prepared in THF and undergoes cyclization in refluxing solvent. The reaction of myrcene with magnesium results in the complex ‘myrcene-magnesium’ which, on treatment with acetyl chloride or acetic anhydride, results in the formation of a three-membered ring. Similar observations have also been recorded for ‘isoprene-magnesium’. The complex [(η-C5H5)2Zr(H)Cl] undergoes 1,2-addition to 1,3-dienes to give complexes (30). Whereas (30; R3 = H) afford bromo-olefins with N-bromosuccinimide, complexes (30; R3 = Me) give cyclopropanes in moderate yields. This unexpected behaviour must be due, at least in part, to the presence of the γ-methyl in (30; R3 = Me), a feature not discussed by the authors. The same zirconium complex undergoes reaction with homoallylic halides to give cyclopropanes in low to moderate yields.

A new facile route to chrysanthemate analogues by 1,5-elimination from 6-bromo-alk-4-enoates and by 1,7-elimination from 8-bromoalka-4,6-dienoates has appeared.

The base-catalysed ring contraction of substituted cyclobutanes continues to attract attention and has been used for the synthesis of bicyclo[n,1,0]alkyl derivatives (n = 3 or 4) of known configuration. However, when applied to chlorotrialkylcyclobutane-1,3-diones, cyclopropanone-2-carboxylates are not obtained; instead, ring cleavage occurs to give γ-chloro-β-keto-esters, perhaps because of the ring strain associated with cyclopropanone. The dione (31), a a photoproduct from bicyclo[2,2,1]hept-5-ene-2,3-dione reacts rapidly with methanol to give (32) (stereochemistry not specified), and cyclobutane-1,2-diones are the probable intermediates in the ring contraction of (33) and its 3-alkyl and 3,4-dialkyl derivatives, brought about by bromination and subsequent hydrolysis.

The α-chlorocyclobutanones (34) and (35) and their 2,3-dihydro-analogues have been subjected to photochemical study. Whereas (34) and (35) are stereospecifically converted into (36) and (37), respectively, with base, photolysis of (34) gives (36), (37), and the ring-cleaved diene in a ratio of 2:6:1 (Scheme 3). However, the endo-chloro-compound (35) gives mainly ring-cleaved diene upon irradiation; (36) and (37) are present, but in low yields. The 2,3-dihydro-analogues give stereoisomeric mixtures of ring-contracted products only. The reaction is believed to proceed by chloride-ion loss in the excited state and carbonium ion rearrangement to a cyclopropyl acylium ion.

(Continues…)Excerpted from Alicyclic Chemistry Volume 6 by M. A. McKervey. Copyright © 1978 The Chemical Society. Excerpted by permission of The Royal Society of Chemistry.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Excerpts are provided by Dial-A-Book Inc. solely for the personal use of visitors to this web site.