Alicyclic Chemistry Volume 4

A Review of the Literature Published During 1974

By W. Parker

The Royal Society of Chemistry

Copyright © 1976 The Chemical Society
All rights reserved.
ISBN: 978-0-85186-582-9

Contents

Chapter 1 Three- and Four-membered Rings By S. A. Math, 1,
Chapter 2 Five- and Six-membered Rings and Related Fused Systems By D. G. Morris, 196,
Chapter 3 Medium- and Large-ring Compounds By E. J. Thomas, 278,
Chapter 4 Bridged Carbocyclics By J. Carnduff, 345,
Author Index, 489,

CHAPTER 1

Three- and Four-membered Rings

BY S. A. MATLIN

1 Introduction, Theory, and Structure

Since the last Report, the number of publications relevant to this chapter has increased by 35 %. There have been numerous reviews and articles concerning aspects of the chemistry of three- and four-membered rings.

Amongst theoretical calculations for these systems is included a quantum chemical study of the π-electron delocalization in triphenylphosphonium ylides, leading to an evaluation of the criteria for reactivity and aromaticity in the Wittig reaction. It was predicted that the as yet unknown ylide (1; X = PPh3) will not take part in the Wittig reaction.

Geometry-optimized INDO calculations on substituted cyclopropenyl cations indicate that F and NH2 groups conjugate strongly with the ring whereas resonance interaction of a phenyl substituent is weak. Stronger conjugation of all three substitu-ents is seen with the cyclobutadienyl dication. In spite of the strong polarization of the carbonyl group in cyclopropenone (1: X = O) there was very little indication of charge build-up in the ring or of aromatic character, but protonated cyclopropenone does resemble a 2π aromatic system. Comparisons of cyclopropenone with thiiren 1,1-dioxide have also been made.

Using graph-theoretical technique, Hearndon and Ellzey have identified, within the Hückel MO formalism, a new class of π-structures containing even numbers of π-orbitals of which 2-cyclopropenylallyl is the smallest member. This has a closed shell of electrons according to HMO theory, but is required to have a biradical valence bond structure, and dicationic species should be obtainable.

From a graphical study of positional isomers containing bivalent sulphur, it was predicted that (2a) should be more stable than (2b). The former has been synthesized, whereas the latter is not a known compound.

Following the development of the MINDO/3 method, which is considerably more successful than MINDO/2 in taking account of strain factors, the possibility of collapse of bisdehydrobenzenes (3) to bicyclic structures has been examined. The most striking conclusion was that (3a) should have a stability comparable to that of o-benzyne, and this suggests that m-benzynes may be viable reaction intermediates.

MINDO/3 calculations of the cycloreversion of vinylcyclobutane to ethylene and butadiene show a biradical transition state to be involved, and the cycloaddition of cyclobutadiene and acetylene, affording Dewar benzene (4), was also examined. The equilibrium geometry of the latter, predicted by semi-empirical INDO calculations, was in good agreement with experimental results and the calculated dipole moment of <0.04 D suggests that the likelihood of obtaining a microwave spectrum is marginal at best.

The calculated potential curves for the (CH)3CH2+ system show that the cyclo-propenylcarbinyl, cyclobutenyl, and bicyclobutyl cations are surrounded by relatively low-energy barriers and that they would readily collapse to the most stable conformer, the puckered homocyclopropenyl cation (5).

The iterative maximum overlap approximation (IMOA) method is useful for the semiquantitative prediction of the geometry of hydrocarbons, and has been applied to several cyclopropyl and cyclobutyl derivatives. An intramolecular force field for amides has been derived and used to calculate the crystal structure of cyclopro-panecarboxamide.

Several X-ray structure determinations of three-membered-ring compounds have been reported, including a cyclopropenium salt, 7-PO-substituted norcaradienes (6; X = H, Cl, or Br), chrysanthemic acid derivatives, and 1,6:8,13-cyclopro-panylidene[14]annulene (7). The photoelectron spectrum of (7) has also been reported.

Squaric acid and its derivatives continue to be the subject of detailed X-ray examinations. Evidence for strong intramolecular H-bonding has been obtained. This is of two types in the acid, with O · · · O distances of 2.532 and 2.544 Å, and whilst the acid is planar it is not square but asymmetric.

Whereas the cyclobutane rings in (8; X = O or S) are planar, that in (9) is puckered, and two short Br · · · Br distances of 3.55 Å are observed in the crystals. Planarity is also seen in cis-cyclobutene-3,4-dicarboxylic acid and in substituted cyclopentadi-enyl cobalt complexes of tetraphenylcyclobutadiene, in which each metal atom is sandwiched between parallel, planar four- and five-membered rings. Crystal structures have been obtained for a variety of polycyclic compounds containing cyclobutane rings.

Photoelectron spectroscopy is a method of growing importance for structural investigation, particularly for revealing the fine details of bond interactions. Thus, the technique has been used to demonstrate σ–σ conjugation between the C — Sn bond and cyclopropane orbitals in cyclopropylcarbinyltrimethyltin, hyperconjuga-tion in unsaturated small rings, and inductive and conjugative interactions in cyclo-propenones. In contrast to the theoretical calculations outlined above, the photo-electron spectroscopy data suggest that there is indeed some resemblance between cyclopropenone and the aromatic cyclopropenyl cation.

Photoelectron spectral data indicate much weaker interactions between a four-membered ring and a π-system than between a three-membered ring and a π-system.

The photoion spectrum of cyclopropane has been measured, giving appearance potentials in good agreement with those obtained from photoelectron spectroscopy.

Conformational aspects of small-ring carbocycles have been reviewed and a linear combination of hybrid orbitals treatment has been applied to cyclobutane.

I.r. and n.m.r. show the gauche conformation (10a; X = H, φ = 45 [+ or -] 10°) of bicyclopropyl to be more stable than the s-trans (10b) by ca. 150 cal mol-1 but the rotation angle (φ) is considerably increased in meso-2,2,2′,2′-tetrahalogenobicyclo-propyls (10a; X = Cl or Br, φ = 166°).

Optical activity in high-symmetry chiral molecules has been discussed, and the importance of the role of conformational dissymmetry emphasized by comparison of allenes and spiro[3, 3]heptanes. Baboulène and Sturtz have discussed the relationship between stereochemistry and pharmacological activity in 1-aminomethyl-2-benzoylcyclopropanes.

Included in reports of thermochemical studies are estimates of the heats of formation and strain energies of the azoalkenes (11) and (12) and hydrocarbon (13).The conversion of the azoalkenes into bicyclo [n, 2, 0]alkanes is now suggested to be much less exothermic than previously estimated.

2 Synthesis of Three-membered Rings

Condensation Reactions. — Trost has reviewed the preparation and synthetic uses of cyclopropyldiphenylsulphonium ylides. The regioselectivity and chemospecificity of the cyclopentane and cyclopentenone annelation reactions have been examined.

Whereas diphenylsulphonium methylide does not cyclopropanate simple, un-activated olefins such as tetramethylethylene, transfer of a methylene group from the ylide can be effected stereospecifically in the presence of a copper catalyst and this reaction may provide a model for biological cyclopropanations by the ylide derived from S-adenosyl-methionine. Attempts to catalyse a similar transfer to unactivated olefins using PdCl2 were not successful.

The ylide (14), stabilized by both sulphonium and phosphinyl substituents, has been prepared and reacts with Michael acceptors to give phosphonocyclopropanes. The same cyclopropane (15) results from addition to both maleate and fumarate, implicating the betaine (16) as a common intermediate.

As reported earlier by Trost, racemization of chiral sulphonium ylides inhibits their utility for asymmetric cyclopropanations. The rates of racemization of a series of sulphonium acylylide derivatives have now been measured and their ease of racemization and reduced nucleophilicity compared with simple sulphonium ylides noted. It seems that chiral sulphonium ylides will serve as useful asymmetric transfer reagents only when significant free-energy differences exist between diastereomeric transition states.

Condensation of the enol ethers of β-dicarbonyl compounds with dimethylsul-phonium methylide generally takes place by attack on the carbonyl group, leading to furans. However, enol ethers derived from (β-keto-aldehydes are attacked first at the double bond to give cyclopropanes. These further react at the carbonyl group, the resulting cyclopropyl epoxides rearranging to dihydropyrans (Scheme 1).

Tropone is cyclopropanated in good yield at the 2,3-double bond with phenacyl dimethylsulphonium ylide.

A number of cyclopropyl ketones have been prepared by reaction of αβ-unsaturated ketones with dimethylsulphoxonium methylide. With the aid of kinetic results, the principal factors governing the reactivity and stereochemistry of the cyclopropanes were analysed. From both cis and trans acyclic enones, only E-cyclopropyl ketones were isolated, the trans-isomer reacting much faster than the cis and the products being formed via conformationally equilibrating zwitterionic intermediates. It was noted that much less stereoselectivity was observed when the acyl group of the enone was replaced by a CN function. With conjugated cyclohexenones, the conformational changes in the intermediates are suppressed so that epimerizations are not observed. The stereochemistries of the cyclopropyl ketones formed then reflect the direction of attack of the ylide on the ring, with axial attack at C-3 of the enone being favoured in the absence of steric effects.

The condensation of dimethylsulphoxonium methylide with ethylenic ketones may be successful when other methods, such as the Simmons-Smith procedure, fail, as for example in the reaction with pyridyl styryl ketones which gives trans-cyclo-propanes in moderate to good yields.

Attack occurs exclusively at the least substituted double bond of the seven-membered ring in the cyclohepta[c]thiophens (17; R = H or Me), and similar specificity is seen with the cyclohepta[b]thiophens (18a) and (18b). Compound (19) affords a mixture of two products.

Phenalenone (20; R = H) did not give the expected cyclopropylketone (21; R = H) on reaction with dimethylsulphoxonium methylide, attack at the 9-position instead generating the betaine (22), which collapsed to 9-methylphenalenone (20; R = Me). However, treatment of the latter gave the cyclopropane (21; R = Me).

Steric effects on the formation of 6,7-methano-steroids from steroidal 4,6-dien-3-ones have been examined. The results (Scheme 2) show that the reaction is governed by steric approach control, as axial attack from the least hindered side would give α-cyclopropanation. Van der Waals attractive forces of the 10β methyl group are probably not involved, as the rates are A, B > C, D, F > E, indicating a rate-retarding effect of the 10β and 11β substituents. The most likely explanation is that the initial step of ylide addition to the dienone is reversible and axial (α) attack is preferred. However, the second step is subject to secondary steric interactions caused by tor-sional changes in forming the final ring system, and it appears that ring-closure to form α-methylene adducts with a 10β methyl substituent is inhibited by diaxial inter-actions involving the functions at 8β, 10β, and 11β. In the case of the 19-nor-dienes A and B these interactions are minimized, and product formation is governed by the concentration of the most rapidly formed α-intermediate.

Both cis– and trans-1,2-diphenylcyclopropanes, on treatment with DMSO-, afford exclusively the trans-cyclopropane after work-up, which is taken as evidence that cyclopropanes are not intermediates in the alkylation of activated double bonds with DMSCT-.

Further details have appeared of the condensation of the diraethylsulphoxonium ylide (23; R = H or Me) with αβ-unsaturated carbonyl compounds, which were discussed in an earlier Report. In the attempted alkylation of the ylide (24) with phenacyl bromide the ylide functions solely as a base, trans-1,2,3-tribenzoylcyclo-propane being the sole product formed in high yield.

Cyclopropanes are formed in the condensation of epoxides with ylides derived from phosphonates. Attempts to carry out similar reactions with phosphonium ylides were generally unsuccessful, an exception being the reaction of the phosphonium halide (25) with oxiran.

The bis-ylide (26) is alkylated by dibromoacetone and in the presence of excess ylide the initial product cyclizes, providing a route to cyclopropyl ketones.

The condensation of stabilized carbanions with epoxides, activated olefins,or alkanes bearing a good leaving group β to a second good leaving group, or a carbanion-stabilizing function, provides a general series of routes to cyclopropanes. In the reaction of the phosphonate (27) with methacrylate in the presence of sodium hydride, a mixture of cis- and trans-isomers of the phosphonate-substituted cyclopropane (28) was obtained in all solvents examined. A plot of the logarithm of the trans/cis ratio against the Kirkwood–Onsager term for solvent polarity gave a straight line, with the slope being the inverse of that found in nearly all similar cases previously reported, i.e. the cis-isomer predominates in polar solvents and the trans in non-polar media. This inversion of the solvent–isomer ratio relationship was seen as a consequence of the presence of the polar, activating phosphonate group and the result is consistent with the general concept of sterochemical control by transition-state dipole-solvent interactions proposed by Inouye. It should be noted, however, that the assignment of configuration to the cyclopropanes was based essentially on n.m.r. evidence, and a rigorous examination of product geometries is clearly important in a case of this type.

The kinetically controlled product of condensation of t-butyl isocyanide with acetylene dicarboxylic ester has been shown to have the bicyclobutane structure (29).

Intramolecular Cyclizations. — Theoretical calculations have been reported for the conversion of 1,3-disubstituted propanes into cyclopropanes. Metal-promoted eliminations in 1,3-dihalogenoalkanes afford cyclopropanes, generally in good yields.

The trans-1,2-dipropylcyclopropane formed in the Li(Hg)-induced debromination of R,R-4,7-dibromononane is generated with inversion of configuration at both centres. This stereochemical result rules out the possibility that the popular ‘π-cyclo-propane’ takes part as an intermediate, and suggests a process in which metal–halogen exchange is followed by an internal displacement of the second halide group. The stereoconvergence observed in such cyclization reactions (i.e. formation of the same mixture of cis/trans isomeric reaction products from diastereomeric dihalides) strongly suggests a non-concerted mode of reaction.

Evidence for a two-step mechanism has been adduced in the electrochemical reduction of 1,3- and 1,4-dibromides. For 1,3-dibromopropane studied by cyclic voltammetry in DMF solution with a silver-coated platinum electrode at moderately low sweep rate (0.3 V s-1), surprisingly, two irreversible waves were observed. The results obtained were suggestive of a mechanism involving two irreversible one-electron transfers, such as:

[FORMULA NOT REPRODUCIBLE IN ASCII]

Cyclopropanes are formed by the intramolecular insertion of a carbene into a C — H bond. A MINDO/2 study of the rearrangement of singlet ethylmethylene to propene and cyclopropane revealed that olefin formation (hydrogen migration) presents no energy barrier, but a critical energy of 1.4 kcal mol-1 was found in the pathway to cyclopropane formation.

Intramolecular cyclization occurs when a carbanion is generated γ to a leaving group. Carbanion-stabilizing functions are carbonyl, cyano, nitro, and pyridylgroups whilst leaving groups may be halide, mesylate, and triflate. An example involving the latter is the ethoxide-ion-induced cyclization of (30) to (31) which takes place in 65 % yield at room temperature. It is noteworthy that closure to the three-membered ring is preferred to cyclopentanone formation.

trans-Di-t-butylcyclopropanone (33) has been prepared by the action of potassium t-butoxidc on the bromoketone (32) and partly resolved by asymmetric destruction with d-amphetamine. The isomer ( + )-(33) racemizes at 80°C and decarbonylates at 150°C or on irradiation. (Further reactions of this rare example of an isolable cyclopropanone are detailed on p. 102).

An improved two-step synthesis of cyclopropane-carboxylic ester from γ-butyro-lactone makes use of a base-induced elimination:

[FORMULA NOT REPRODUCIBLE IN ASCII]

Rate and product studies of the 1,3-deoxystannylation of 3-stannylalcohol derivatives implicate a concerted mechanism for cyclopropane formation. This elimination reaction has been developed into a general synthesis of cyanocyclopropanes, based on the condensation of lithium tributyl-(2-cyanoethyl)tin with carbonyl compounds (Scheme 3).

Oxidation of compound (34) with lead tetra-acetate affords the cyclopropane (35). This is the first observation of a homovinylic oxidation of a 2-pyrazoline.

Further details of the alkylation of eucarvone anions have appeared, as have full studies of the previously reported photocyclization of 3-amino-ketones (36) to 2-amino-cyclopropanols.

Irradiation in benzene of 4-butyroylpyrimidine (37) affords a 60:40 mixture of the cyclopropanol (38) and cleavage product (39). Only the former product is formed when t-butyl alcohol is used as solvent and only the latter in hexane. These results are best accounted for by formation of an n-π* triplet which abstracts a γ-hydrogen (a process rarely seen with nitrogen aromatic ketones), giving a 1,3-biradical which can ring-close. Fragmentation could come from the 1,3-biradical or from alternative 1,4-biradical formation. The solvent effects have not yet been clearly explained.

(Continues…)Excerpted from Alicyclic Chemistry Volume 4 by W. Parker. Copyright © 1976 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.