Professor Hanson is Emeritus Professor of Chemistry at the University of Sussex.

Terpenoids and Steroids Volume 8

A Review of the Literature Published between September 1976 and August 1977

By J. R. Hanson

The Royal Society of Chemistry

Copyright © 1978 The Chemical Society
All rights reserved.
ISBN: 978-0-85186-326-9

Contents

Part I Terpenoids,
Chapter 1 Monoterpenoids By R. B. Yeats, 3,
Chapter 2 Sesquiterpenoids By T. Money, 64,
Chapter 3 Diterpenoids By J. R. Hanson, 123,
Chapter 4 Triterpenoids By J. D. Connolly, 150,
Chapter 5 Carotenoids and Polyterpenoids By G. Britton, 181,
Part II Steroids,
Chapter 1 Physical Methods By O. N. Kirk, 211,
Chapter 2 Steroid Reactions and Partial Syntheses By B. A. Marples, 227,
Errata, 282,
Author Index, 283,

CHAPTER 1

Part I

TERPENOIDS

1

Monoterpenoids

BY R. B. YEATS

The format established in previous volumes is maintained, except that a consolidation this year brings all monoterpenoid biosynthetic work into this chapter; in keeping with previous practice, metabolic functionalization of monoterpenoids is reported in the relevant structural sections and not under Biogenesis. The number of monoterpenoid papers published this year appears to have increased, although a decline is noted for papers on essential oi Keeping abreast of this burgeoning literature, especially by means of alerting services and computer data bases, could be made easier if all authors and editors selected titles more judiciously and insisted upon the inclusion of keywords. For example, it is noted that, to the uninitiated, the title of Trost’s full paper on grandisol and fragranol synthesis (cf. Vol. 6, p. 21) gives too little clue of its content; the same is true of McMurry’s perillene synthesis, and even the author’s own abstract provides no clue of the inclusion of a yomogi alcohol synthesis in the paper by Wada et al Such inadequacies result in an unnecessary shortfall in the number of monoterpenoid-related papers retrievable by the use of anticipatable keywords in alerting services such as Current Contents, Science Citation Index, and Index to Scientific Reviews when compared with this Reporter’s literature search. The inability to retrieve references to previous Reports on monoterpenoids in this series by the use of Index to Scientific Reviews is, fortunately, not repeated in Lewis’s valuable index.

The use of Chemical Abstracts as an alerting service again reveals some apparently inconsistent abstracting and misplaced abstracts. Examples include the unnecessary separation of abstracts referring to Volume 6, the classification of a paper on cis-3,4-Δ1-THC under alkaloids, and the inclusion of the non-terpenoid C11 compound pestalotin under Terpenoids, especially when neither Cavill’s characterization of the cyclopentane monoterpenoid dolichodial and related compounds nor the identification of new limonene metabolites is even cross-referenced. Papers on the characterization of iridoids are rarely found under Terpenoids, and cross-referencing to and between Carbohydrates and Plant Biochemistry, where papers seem to be located at random, is poor. It would also be helpful to translate more than a title for abstracts based upon Referativnyi Zhurnal, Khimiya.

The prompt compilation of future Reports will be helped substantially if monoterpenoid chemists would be willing automatically to send reprints of papers, particularly of articles published in less accessible journals, directly to this Reporter.

1 Physical Measurements: Spectra etc.; Chirality

A review of 1H n.m.r. spectra of cyclic alkenes points out the need to re-examine car-2-ene and car-3-ene conformations (cf. Vol. 5, p. 41). Further 1H n.m.r. data on methyl-substituted norborneols in the presence of [Eu(dpm)3] shift reagent have been reported. Attempts to correlate calculated and experimental lanthanide-induced shift data could not distinguish between diastereomeric esters of trans-myrtanoic acid, gave poor results with the 4-aminoborneols, and, although readily distinguishing between cis- and trans-pinocarveol, could not distinguish between proposed conformations with certainty. The use of [Eu(fod)3] with Mosher’s reagent esters of diastereomeric secondary alcohols (e.g. borneol/isoborneol, cis-carveolltrans-carveol, isopinocampheol/neoisopinocampheol) allows configurational assignments at the carbinol centre by observing the magnitude of methoxy lanthanide-induced shifts and should be valuable in assigning stereochemistry in diastereoselective reductions of ketones. The absolute configuration of chiral thiols can be determined from the 1H n.m.r. spectra of the diastereomeric hydratropic thioesters. The observation that the well known iridoid aucubin is readily identified in an intact seed of Aucuba japonica may signal a useful monitoring role of 13C n.m.r. spectroscopy in plants.

The bathochromic–hypochromic shift in the U.V. spectra of umbellulone and verbenone has been interpreted as being due to extension of the αβ-unsaturated carbonyl chromophore. U.V. and c.d. data into the vacuum region have been recorded in the vapour phase and in solution for α- and β-pinene, camphene, bornene, fenchylidenefenchane, and bornylidenebornane; the major c.d. bands were assigned. Whilst calculated rotatory strengths of cisoid dienes of fixed conformation are in good agreement with experimental results, calculations on the conformationally flexible α-phellandrene fail to give good agreement. The value and limitations of using n-propylammonium (+)-camphor-10-sulphonate as a standard for c.d. and o.r.d. calibration have been discussed further. Variations in the rotivities of (-)-α-pinene and (+)-limonene with temperature and solvent are reported.

The discussion of a series displacement index for classifying mass spectra and for correlation with structural stability includes some monoterpenoids (e.g. myrcene limonene, santene).

Rate constants are reported for the reactions of α- and β-pinene and of (+)-limonene with OH radicals so that comparison is now possible with those from reaction with O(3P) (see Vol. 7, p. 6) and with ozone (see Vol. 6, p. 8); results are consistent with those calculated from the data of Grimsrud et al. (Vol. 6, p. 8) from which further rate constants for the reaction of nine other monoterpenoid hydrocarbons with OH radicals have been calculated. In the oxidation of sterically unhindered alcohols (e.g. borneol, the pinocampheols, the nopinols), the reaction rate correlates with the strain difference between the alcohols and the derived ketones, suggesting that the properties of the carbonyl group are reflected in the oxidation transition state. A second paper reports Sicher correlations for the chromic acid oxidation of epimeric alcohols (e.g. the isoverbanols). Attempts have been made to calculate the proportions of epimeric alcohols formed on complex metal hydride reduction of cyclic ketones by considering steric congestion and torsional effects, interpreting the results in favour of a mechanism involving initial complexation between the ketone and the reagent followed by rate-determining nucleophile transfer. Camphor and isopinocamphone calculations bear out known epimeric alcohol proportions but agreement for the hindered fenchone and for chrysanthenone is not good. In chrysanthenone reduction the major predicted product is not in keeping with that which is observed; the authors suggest that the original assignment of product stereochemistry may be in error, without reference to recent work. Another approach for substituted cyclohexanone reduction by NaBH4 in propan-2-ol, which is based upon free-energy increments for non-polar substituent groups, gives good agreement between theory and experiment for menthone.

The adsorption of (+)-camphor-10-sulphonate ions on a mercury electrode is a two-dimensional associative adsorption of ions as micelles in equilibrium with free adsorbed ions (cf. camphor and borneol, Vol. 5, p. 4).

The factors affecting asymmetric electrochemical reduction of (-)-menthyl phenylglyoxylate have been examined. Asymmetric homogeneous catalytic hydrogenation of substituted cinnamic acids (in up to 70% enantiomeric excess) with [Rh(cod)Cl]2-(-)-menthylmethylphenylphosphine catalyst is probably more influenced by the chirality at phosphorus than that at carbon, with results similar to those obtained with a (-)-neomenthyldiphenylphosphine ligand which is also reported to yield 95% of (3R)-(+)-dihydrogeranic acid from geranic acid (E : Z/9:1). Much useful asymmetric synthetic work has centred on boron reagents. Lithium B-isopinocampheyl-9-borabicyclo[3,3,1]nonyl hydride reduces ketones to R-alcohols in up to 37% enantiomeric excess; the reagent is readily available from B-isopinocampheyl-9-borabicyclo[3,3,1]nonane, the product of hydroboration of (+)-α-pinene with 9-borabicyclo[3,3,1] nonane; oxidation of B-isopinocampheyl-9-borabicyclo[3,3,l]nonane yields isopinocampheol (1; 99.9% optical purity) and it can also be used for the highly enantioselective reduction of aldehydes (e.g. [α-2H]benzaldehyde to the corresponding S-alcohol in 90% enantiomeric excess; a modification yields the R-alcohol) with the promise of chemo-selectivity also. Monoisopinocampheylborane, which is readily available from the corresponding triethylamine complex hydroborates trisubstituted alkenes leading to alcohols of S-configuration in up to 72% enantiomeric excess; useful asymmetric reductions of ketones with di-isopinocampheylborane of high optical purity, two syntheses of which have been reported, as well as nearly complete asymmetric induction in the hydroboration-oxidation of cis-but-2-ene have been discussed. The full paper on the asymmetric reduction of acetophenone with monoterpenoid glycol-lithium aluminium hydride complexes (Vol. 7, p. 5; cf. Vol. 4, p. 5) has been published as well as further synthetic work on S-(+)-2,2,2-trifluoro-1-phenylethanol (Vol. 7, p. 4) and on its resolution as (-)-ω-camphanic acid esters; the latter is one of a number of examples in which resolution via(-)-ω-camphanic esters is monitored by 1H n.m.r. in the presence of [Eu(fod)3] or [Eu(dpm)3] [see Vol. 4, p. 4; formula (4) should have the alkoxycarbonyl group attached to the bridgehead position]. In an extension of previous work (Vol. 6, p. 6), the asymmetric reduction of ethyl benzoylformate with the NAD(P)H model system (2kmagnesium perchlorate is best when X=NH; the inability of horse liver alcohol dehydrogenase to reduce fenchone and camphor is consistent with the diamond lattice section model of the active site and accounts for the HLADH-catalysed oxidation of ([+ or -])-(3) to the ‘unnatural’ (-)-cis-tetrahydroactinidiolide (258) (p. 60) in 14% optical purity. Such reactions must be interpreted with care in view of the observation that N-benzyl-1,4-dihydronicotinamide acts as an electron donor in the reduction of 2-exo-bromo-2-endo-nitrobornane.

The synthesis and use of peroxycamphoric acid as an asymmetric oxidizing agent has been re-evaluated.

Other interesting examples of asymmetric syntheses involving chiral monoter-penoids include the Claisen reaction between (-)-menthy1 phenylacetate and benzaldehyde (optical purity is confirmed by microcalorimetry), a highly enantioselective carbenoid cyclopropanation catalysed by (4), and the crossed aldol addition of silyl enol ethers as well as the addition of allyltrimethylsilane to (-)-menthyl keto-esters; in the latter case the product stereochemistry was tentatively assigned according to the Prelog generalization, which is not applicable to Reformatsky reactions of (-)-menthyl and (+)-bornyl pyruvates. Applications involving chiral centres other than carbon include organosilane synthesis, the reaction of (-)-menthyl (-)-(S)-toluene-p-sulphinate with Grignard and organocopper-lithium reagents, and selenonium ylide formation.

Asymmetric hydrolysis of ([+ or -])-menthyl acetate by Rhodotorula muciluginosa is reported.

A method for determining optical purities of less than one percent for secondary alcohols has been published, and Mislow has observed a partial resolution which may serve to distinguish between a meso and a racemic host product when a derived inclusion compound is recrystallized from an enantiomerically enriched guest solvent.

G.l.c. papers of interest include the classification of 22 acyclic monoterpenoid alcohols according to retention indexes, resolution of cyclic ketones [e.g. ([+ or -])-menthone, ([+ or -])-isomenthone] as diethyl (+)-tartrate acetals, and the use of lanthanide shift reagents to resolve non-terpenoid racemic epoxides. The occurrence and prevention of monoterpenoid hydrocarbon isomerization during silica gel chromatography has been examined and the separation of monoterpenoids and sesquiterpenoids by gel permeation chromatography is reported. Monoterpenoid hydrocarbons have been selectively extracted from essential oils using dimethylsilicone.

2 General Synthetic Reactions

Some useful reviews which discuss applications from, or are of value to, monoter-penoid chemistry include applications of diborane reductions, transition metals in organic synthesis, O-silylated enolates, the Barbier reaction, selenium dioxide oxidation, Birch reduction of αβ-unsaturated carbonyl compounds, and homogeneous hydrogenation catalysts. A broad overview of organoboranes has been published. Kagan has reviewed the use of graphite insertion compounds.

Less substituted αβ-unsaturated cycloalkenones rearrange by double-bond migration around the ring to the more substituted αβ-unsaturated cycloalkenones in high yield, catalysed by RhCl3,3H2O; non-conjugated double bonds also migrate into the ring system to become conjugated; e.g., dihydrocarvone rearranges efficiently to [(5):(6)/7:1]. The thermodynamically favoured isomerization of alkenes (e.g. β-pinene to α-pinene) in sulphur dioxide has been interpreted as a reversible ene reaction; an earlier Report (Vol. 1, p. 43) erroneously alludes to the reaction of β-pinene with sulphur dioxide to form the corresponding cyclic sulphite. Relatively rapid racemization of p-menth-1-ene is also observed in sulphur dioxide. The rearrangement of α-ethylenic and α-acetylenic alcohols (e.g. 1,2-dehydrolinalool to citral, cf. Vol. 7, p. 17) via vanadate esters has been discussed.

Methods for oxidative transformations continue to receive attention. Nickel peroxide on graphite oxidizes geraniol to citral in 89% yield.” Three groups report the oxidative rearrangement of tertiary vinyl carbinols. Linalool is converted smoothly into a 1:1 mixture of E- and Z-citral using pyridinium chloro-chromate (cf. Vol. 6, p. 8; Vol. 7, p. 30); oxidation of linalool with Collins reagent yields only 10% of E- and Z-citral with the epoxides (7) predominating. By analogy with nerolidol, chromous chloride would be expected to convert (7) into E– and Z-citral. Alkylative enone transposition is achieved by the 1,4-addition of trialkylstannyl-lithium-THF to αβ-unsaturated ketones (in contrast the reagent gives 1,2-addition in ether as solvent) followed by alkylation, oxidative destannylation with Collins reagent, and dehydration; ([+ or -])-piperitone (8; X = H) is readily synthesized from 4-isopropylcyclohex-2-enone. Applications of polymeric oxidizing agents include the efficient oxidation of alcohols (e.g. geraniol, menth0l)and allylic halides (e.g. geranyl brumide) to aldehydes and ketones with chromic acid on anion-exchange resin, and sensitized oxidation of the enamino-ketone (9) in the presence of polymer-bound Rose Bengal yields buchucamphor (8; X = OH) in 81% overall yield from menthone. Selenium dioxide allylic oxidation may be effected much more cleanly than with selenium dioxide alone by using t-butyl hydroperoxide in the presence of a catalytic amount of selenium dioxide; e.g., geranyl acetate is oxidized to (E,E) -8-acetoxy-2,6-dimethylocta-2,6-dien-1-0l (48%) and the corresponding aldehyde (7%). Some further details of the photochemical cleavage of pyruvate esters (Vol. 7, p. 6) have been published; when so much of these two papers — results, references, and actual paragraphs — are virtually identical, there seems little need for separate publication. An improved method (high to quantitative yields) for oxidizing alcohols, via dimethylalkoxysulphonium salt, using DMSO-TFAA followed by base at very low temperatures, works well with sterically hindered alcohols; isoborneol yields camphor at low temperature (>90%) but camphene (>85%), by rearrangement-elimination, when the base treatment is at room temperature. Other oxidation papers of interest include alkali hypochlorite oxidation catalysed by RuO2 (chrysanthemyl alcohol to chry-santhemaldehyde), the full paper which extends earlier observations (Vol. 4, p. 6) on the oxidation of saturated secondary alcohols with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, halothiation as a method for oxidizing primary halides and terminal alkenes (e.g. β-pinene; low yield) to aldehydes, and the oxidation of secondary alcohols by trichloroacetaldehyde on alumina (e.g. menthol to menthone, plus some isomenthone); homogeneous catalytic oxidation of secondary alcohols with O2-PdCl2-NaOAc fails in the presence of alkenes (e.g. p-menth-8-en-3-ol).

(Continues…)Excerpted from Terpenoids and Steroids Volume 8 by J. R. Hanson. Copyright © 1978 The Chemical Society. Excerpted by permission of The Royal Society of Chemistry.
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