Part I

TERPENOI DS

Monoterpenoids

BY R. B. YEATS

1 Introduction

This year's Report surveys the literature up to August 1978, subject to its availability in Europe by early November 1978. A few additional papers of particular significance which were published between August and December 1978 have been included for added clarity. Further changes for this Report concern halogenated monoterpenoids and the consolidation of monoterpenoid X-ray crystallographic structure determinations into a separate section. The X-ray analysis of monoterpenoids has been increasing significantly. Unfortunately it is not always possible to identify such structure determinations in earlier Reports. Since previous Reports and lists of X-ray structure determinations were incomplete or inaccurate, it seems timely to include in this new section references to all monoterpenoid X-ray crystal structure determinations which have been reported in the literature to date.

Authors are reminded of a request made earlier (Vol. 8, p. 4) concerning sending reprints of monoterpenoid-related papers automatically to this Reporter to assist the prompt compilation of future Reports.

The restricted space available for these Reports unfortunately does not allow the discussion of a number of topics of interest to monoterpenoid chemists; useful reviews of such topics include monoterpenoid alkaloids, carbazole alkaloids, isoprenoids and alkaloids of tobacco, naturally occurring plant coumarins, the biosynthesis of aromatic hemiterpenes, and recent developments in the field of naturally occurring aroma components. The poor quality of the Chemical Abstracts makes it difficult to assess the significance of a number of reviews of potential industrial interest. A volume in the 'Methodicum Chimicum' series includes a very brief discussion of some monoterpenoids.

Three useful reference works have been published. Some acyclic monoterpenoids containing one chiral centre are included in lists relating the sign of optical rotation (no numerical values are given) and absolute stereochemistry with the method of structural correlation; unfortunately the literature has only been covered to 1971. In contrast, Klein and Rojahn have included literature references to October 1976 in the literature report which accompanies their wall-chart of monoterpenoid configurations. In an otherwise excellent and most useful work, attention is drawn to four misprinted formulae [(+)-trans-myrtanol, (-)-piperitenone epoxide, (+)-piperitone epoxide, and (-)-junionone] and the omission of the iridoids, the naturally occurring halogenated monoterpenoids, and some well-known cycloheptane monoterpenoids. It is always difficult to be all-inclusive; however, a significant number of monoterpenoids appear in only one or the other of these works. The graphic assembly of formulae from Dragoco also illustrates the array of inconsistent nomenclature practices which have grown up with the literature [e.g. thujone (isothujone), Δ4-carene (car-2-ene), inconsistent o-menthane nomenclature, 2,6-dimethylocten-1-diol-(3, 8) (cf.) 3,7-dimethyloct-7-en-1,6-diol), myrcenol vs. myrcen-8-ol]. Surely the time has come to .adopt a standardized monoterpenoid nomenclature.

Few of the recently published reference books covering natural products provide the chemist, within a single volume, with most of the detail which is frequently required, viz. names, structure, physical data, together with references to occurrence, structure determination, and synthesis. The revised edition of Karrer, and its first supplement, do provide this detail in their comprehensive coverage of plant products. This strength makes these volumes indispensable, despite the delay in covering the literature, viz. to 1956, and 1957 — 61 respectively. Newly isolated monoterpenoids now occupy a class of their own in the first supplement, although some cycloheptane monoterpenoids (e.g. β-dolabrin), quinones (e.g. β-thujaplicinol), and tetrahydrocannabinol (the formula is incorrect) are listed separately.

2 Physical Measurements: X-Ray Crystallography; Chirality

X-Ray Crystallography. — In addition to 43 new structure determinations reported this year, the list of X-ray structure determinations of monoterpenoids (and closely related compounds falling within the scope of these Reports) which follows includes compounds reported directly in earlier volumes (to which references are made); original literature references are given for all other structures, whether newly reported from 1946 to August 1978.

2,6-Dimethyloctanes. Geranylamine hydrochloride.

Naturally Occurring Halogenated Monoterpenoids. (3R,4S,7S)-trans,trans-3, 7-Dimethyl-1,8,8-tribromo-3,4,7-trichloro-octa-1,5-diene (Vol. 7, p. 18, ref. 200); violacene 2 (1; X = Cl) (Vol. 7, p. 19, ref. 209); costatol (Vol. 8, p. 31, ref. 301); costatone (Vol. 8, p. 31, ref. 302); a reassigned structure for violacene (2); chondrocolactone (3); (1R,2S,4S,5R)-1,4-dibromo-5-chloro-2E-chlorovinyl -1,5-dimethylcyclohexane (1; X = Br); and (1S,2S,4R,5S)-2-bromo-1E -bromovinyl-4,5-dichloro-1,5-dimethylcyclohexane (4).

Chrysanthemyl Derivatives and Pyrethrins. (1R,3R)-(+)-trans-Chrysanthemic acid p-bromoanilide (Vol. 7, p. 20, ref. 213); (4S)-2-(prop-2'-enyl)rethron-4-yl (1R,3R) -trans-chrysanthemate 6-bromo-2,4-dinitrophenylhydrazone (Vol. 4, p. 20, ref. 115 incorrectly refers to the X-ray study of six pyrethrins) (Vol. 5, p. 15, ref. 102); 28c α-cyano-3-phenoxybenzyl cis-3-(2',2'-dibromovinyl)-2,2-dimethylcyclopropanecar-boxylate; cis-3-phenoxybenzyl 3-(2',2'-dibromovinyl)-2,2-dimethylcyclopropanecar-boxylate (Vol. 7, p. 10, ref. 119).

Cyclopentanes, Iridoids, Monoterpenoid Alkaloids. (-)-Bromodihydro-umbellulone (5); (-)- isoiridomyrmecin (6);-iridomyrmecin (7) at -150 °C; loganin penta-acetate monomethyl ether bromide; the rubidium salt dihydrate of monotropein (8; R = H); (-)-sarracenin (Vol. 7, p. 27, ref. 269); (-)-1-O-acetylxylomollin;34a [+ or -])-gentiolactone (9);35 (-)- jasminin aglucone ethyl ether;36 tecomanine methoperchlorate; alkaloid C methiodide; and nitropolyzonamine (10) perchlorate.

p-Menthanes. (-)-Menthyltrimethylammonium iodide; (-)-menthyl 4-bromo-2-nitrobenzoate; (+)-isomenthyl p-bromophenylcarbamate; the (-)- menthoxyacetamide of (+)-trans -2-(o-bromophenyl)cyclohexylamine; (-)- menthyl phenylglyoxylate; (-)-menthyl p-bromophenylglyoxylate; (-)- menthyl (-)-p-iodobenzenesulphinate; (1R,3R,4S)-(-)-menthyl S-methyl (S)p-phenylphosphonothioate; (1R,3R,4S)-(-)-menthyl methyl (R)p-phenyl-phosphonate; trans-dichlorobis(dimethylneomenthylphos phine)nickel(n); trans-dichlorobis(dimethylneomenthylphosphine)palladium(II); trans-dichlorobis(dimethylmenthylphosphine)palladium(n); (+)-a-naphthylphenyl-1-menthoxymethoxysilane; (4R,8R]-(+)-p-menth-1-en-9-ol p-iodobenzoate; the diol (11); (+)-cis-carvone tribromide; 2,4-dibromomenthone; syn- and anti-pulegone toluene-p-sulphonylhydrazones; (+) -[(4S)-carvone]RhIC5H5); Fe(CO)3-pulegone complex; racemic, laevo-, and mixed-crystal carvoxime; optically active, racemic, and solid-solution forms of benzoylcarvoxime; diplatinum tetra(dithiocumate); dibromode-hydrobispulegone; monobromoisodehydrobis pulegone; and the monoter-penoid-related tri-o-thymitide and some clathrates.

m-Menthanes. 3, α-Dimethylstyrene-[Fe(CO3]2 complex.

Cycloheptanes. Thujic acid p-bromophenacyl ester; β-thujaplicin; 3,5,7-tri-bromohinokitiol; 3,7-dibromohinokitiol; 5,7-dibromohinokitiol γ-thujaplicin; and the di-isopropylditropolonofuran utahin.

Bicyclo]2,2,1 heptanes. (+)- Camphor; (-)-, (+)-, and ([+ or -])-camphoroxime; (+)-3-bromocamphor (Vol. 2, p. 38); (+)-8-bromocamphor (Vol. 8, p. 49, ref. 439); endo-3,9-dibromocamphor; 70 3-exo, 9,9-tribromocamphor [Vol. 7, p. 37, ref. 372; formula (179) should have an exo-3-bromo-group]; (+) -3-endo, 9,9-tribromocamphor (Vol. 8, p. 50, ref. 442); (+)-camphor-3-carboxylic acid; (+)-3-p-bromobenzylidenecamphor; (+)- and ([+ or -])-o-chloro-phenyliminocamphor; ([+ or -])-trans-π-camphanic acid (Vol. 3, p. 67, ref. 293); (+)-3-diazocamphor (Vol. 3, p. 62, ref. 269); (-)-2-exo-bromo-2-endo-nitro-camphane; (+)-10-bromo-2-exo-chloro-2-endo-nitrosocamphane; 2-exo-bromo-2-endo-nitrofenchane; 6-endo-bromoisofenchone; (-)-1,7-dibromo-3,3,4-trimethylnorbornan-2-one (Vol. 8, p. 49, ref. 440); 1,7-dibromo-4-dibromomethyl-3,3- dimethylnorbornan-2-one (Vol. 8, p. 50, ref. 441); 2-endo-bromo-6-exo (dimethylamino methyl)fenchane hydrobromide; anhydro-bromonitrocamphane (12); (-)-camphene-8-carboxylic acid; (+)-iso-camphenilanic acid p-bromophenacyl ester; ([+ or -])-carbocamphenilone; syn-2,2'-bifenchylidene E at -120°C; 1-biapocamphane; N-(S)-phenyl-alaninato[(+)-hydroxymethylidenecam phorato]copper(II); bis-(3-nitrocam-phorato)-(2-methylpyridine)copper(II); λ-(+)589-trans-tris-(+)-3-acetyl-camphorato] chromium(III); 1R, 2S, 3S, αR]-3-(α-hydroxybenzyl)-1, 7,7-tri-methylbicyclo[2,2,1]heptan-2-ol; (1R,3S,αR]-3-(α-hydroxybenzyl)-1,7, 7-trimethylbicyclo[2,2,1]heptan-2-one; (2R) (-)-2-[(1S',2R')-1',3'-dithian-2'-y]isoborneol 1'-oxide; and 2,2,5-endo,6-exo, 8,9,-heptachlorobornane. Many papers (e.g. see Vol. 5, p. 207) have confirmed the absolute configuration of (+)-3-endo-bromocamphor-9-sulphonic acid; likewise a number of papers have established the absolute configuration of (+)-camphor-10-sulphonic acid as various salts. For the isoalbene S-benzylthioether (189; X = SCH2Ph) endo 2,6-dimethyl-4-benzylthiotricyclo[5,2,1,0]dec-3-ene) see ref. 61lb.

Bicyclo[3,1,1]heptanes. 2α, 4α-Dibromo-10,β-pinan -3-one; (-)-cis-pinocar-veyl p-nitrobenzoate (Vol. 5, p. 36, ref. 269); the cyclic sulphite of 10,β-pinane-2,3α-diol;3-(N-methylaminomethyl)pinane hydrobromide; 3-(N,N-dimethylaminomethyl)pin 2(10)-ene hydrobromide; (-)-bromo-derivative of paeoniflorin (Vol. 3, p. 71, ref. 308); (+)-bis-(π-pinenyl)nickel (Vol. 3, p. 71, ref. 310; Vol. 6, p. 41, ref. 307); (+)- Fe(CO)3-pinocarvone complex;56 the phosphetan (-)-(13) which is synthesized from (-)-α-pinene and MePCl2-AlCl3; (-)-(1S, 5S)-6,6-dimethyl-2-[(2S)-3', 3',3'-trichloro-2'-hydroxypropyl]bicyclo[3, 1, 1]hept-2-ene tosylate ester (cf. Vol. 8, p. 54); 3-chloronopinone; and 3-bromonopinone.

Cannabinoids and other Phenolic Monoterpenoids.(-)-Bruceol (14; X = OH, Y = H); (-)-bromobruceol (14; X = OH, Y = Br); ([+ or -])-dibromodeoxybruceol (15; X = Br); an acetylcitran [Vol. 7, p. 48, formula (255)] and the corresponding formylcitran; dibromocannabicyclol (16); murrayazoline (17); cyclocymopol monomethyl ether acetate (Vol. 7, p. 48, ref. 454); xanthochymol (Vol. 8, p. 60, ref. 536) and the related isoxanthochymol di-p-bromoben-zenesulphonate; cannabinol; cannabidiol; 6β hydroxy-Δ1-THC-DMF complex at -165 °C; Δ1-tetrahydrocannabinolic acid B (Vol. 6, p. 49, ref. 362); cannabispiran; and the synthetic cannabinoid derivative 8,5a-trans-5a, 9a-cis]-1,8-dimethyl-5a-isopropyl-5a,6,7,8,9,9a-hexahydrodibenzofuran-3-ol (Vol. 6, p. 49, ref. 363).

Miscellaneous. Mustelan 1,1-dioxide (Vol. 7, p. 8, ref. 88); trans-]PtCl(CH2=C-CMe=CH2)(PPh3)2]; trans-[PtCH2=C-CMe=CH2) (C[equivalent to]C-CMe=CH2) (PPh3)2]; 2,7-dimethyloctane-2, 7-diol tetrahydrate; trans-2,7-dimethylocta-2,4,6-triene-1:4,5:8-diolide.

Spectral and other Physical Data. — The 1: 1 adduct camphor–[Eu(dpm)3] illustrates a simple balanced linear regression method for obtaining the equilibrium constant (K) for adduct formation and the limiting chemical shifts, corresponding to complete complexation, for each methyl group; K values determined from data for each methyl group agree very closely. A useful method for preparing small quantities of anhydrous n.m.r. solvents has been published. A two-dimensional Fourier-transformation technique for correlating 1H and 13C chemical shifts, based upon long-range spin-spin coupling, may be used to identify gem-dimethyl groups (e.g.] menthone, camphor) by observing the 1H spectra arising from modulated 13C signals. The assignment of 13C resonances by off-resonance decoupling may be improved by scaling down the proton–carbon splittings to optimum values (e.g. the C-3 triplet and C-4 doublet components for camphor). 13C N.m.r. data are reported for some monoterpenoid 1,3-dithians [citral, citronellal, perillaldehyde, myrtenal, menthone, isopulegone, and carvone (18)], 1,3-dithiolans [citronellal, menthone, isopulegone, (18)], and dithiol Michael-adducts [isopulegone, (18)]. γ-Shift correlations are of value in assigning hydroxy- and bromo-substituent group stereochemistry adjacent to axial methyl or gem-dimethyl groups in substituted cycloxanes. Further n.m.r. data are reported below in the discussion on absolute configuration and optical purity, as well as in individual sections.

Some monoterpenoid stereoisomers (e.g. the pinenes, geraniols, borneols, and menthols) are readily distinguished by ion kinetic energy spectroscopy.

Further discussion of c.d. calibration using (+)-camphor- 10-sulphonic acid has been published (cf. Vol. 8, p. 5). A c.d. investigation of charge-transfer complexes between chiral donors and tetracyanoethylene, dichlorodicy-anoquinone, and Vitamin K3, includes data on monoterpenoids [e.g. (-)- fenchone, (+)-camphor, (+)-3-endo-bromocamphor, (-)-α-pinene, (-)- menthol]; n -> + π* and π -> π* transitions were also investigated in a vapour-phase and solvent-dependent c.d. study of, inter alia, (+)-pulegone, (-)-carvone [(4R)-(18)], (-)-fenchone, and (+)-camphene-1-carboxaldehyde.

Further papers in this section report intramolecular hydrogen-bonding in 2-arylaminomethylenecycloalkanones (menthone, carvomenthone, camphor), the effect of chlorinated solvents on the stability constants of hydrogen-bonded complexes between pyrrole and, inter alia, fenchone, and a correlation of half-wave oxidation potentials with the pKa values of the corresponding conjugate acids (e.g. 3-endo-cyanocamphor).

Absolute Configuration, Optical Purity, Asymmetric Synthesis, Resolution. — Reviews of interest in this section concern methods of determining absolute configurations, discriminating interactions between chiral strategies in optical resolutions, and asymmetric systhesis.

Yamaguchi has extended the use of [Eu(fod)3,] with Mosher's reagent esters (cf. Vol. 8, p. 4), to the determination of absolute configuration and enantiomeric purity of primary alcohols which are chiral at the adjacent carbon. However, methoxy peak separation for (4R, 8R)-(+)-p-menth-1-en-9-ol does not allow enantiomeric purity determination. The determination of absolute configuration and of stereoisomeric composition for enantiomeric (cf. ref. 126b) and diastereomeric (cf. Vol. 8, p. 4) secondary alcohols profits from better resolution in the 19Fn.m.r. spectrum. Rules for determining the absolute configuration of secondary alcohols (e.g. menthol) by observing 13C n.m.r. glycosidation shifts have been proposed (cf. Vol. 8, p. 40).

In contrast, Horeau has developed a simple kinetic method for determining the enantiomeric purity and absolute configuration of chiral secondary alcohols (e.g. menthol) based upon enantioselective esterification with α-phenylbutyric anhydride of known enantiomeric purity. Cholesteric phase formation on adding small amounts (<1 mg) of chiral molecules to nematic has been used to determine absolute configurations of molecules possessing one asymmetric carbon atom (via i.r. rotatory dispersion); the sign of the R-Cotton effect correlates well with absolute configurations [e.g. carvone (18), pulegone, limonene] expressed in ligand volume priority.