Stereoselective synthesis monoterpenes

Another type of rearrangement involving 1,5-asymmetric induction is the ketene aza-Claisen rearrangement, used in the stereoselective synthesis of intermediate 16, a common precursor for the synthesis of monoterpene alkaloids (-)-a-skytanthine, (-)-jV-demethyl-<5-skytamhine, and (+ )-epidihydrotecomanine 649. 

Different approaches have been proposed for the stereoselective synthesis of methylcyclopentanoid monoterpenes with nepetalactone-type skeleton (3-oxobicyclo[4.3.0]nonan-2-one-type) and iridomirmecin-type skeleton (3-oxobicyclo[4.3.0]nonan-4-one-type). We will divide the discussion on the basis of the key reactions used in the S5mthetic strategy. 

Terpenes.- The first total synthesis of the biologically active marine natural product metachromin A (241) has been achieved using an ( )-stereoselective olefination with the phosphonate (240) as the key step. The olefination reaction of the a-cyanophosphonate (242) with ( , )-farnesal (243) has been studied under a wide variety of conditions with a view to optimising (Z)-stereoselectivity.Excellent (Z)-stereoselectivity was achieved and the resulting procedure applied to a stereoselective synthesis of plaunotol (244). Epimerisation and P-elimination of base-sensitive substrates can cause problems in phosphonate- and phosphine oxide-based olefinations. Such reactions have been excluded in a recent report of enantiospecific syntheses of iridoid monoterpene lactones by intramolecular phosphonate-olefination through the use of mild bases such as DBU and di(wopropyl)ethyl amine/lithium chloride. 

Since the chemical addition of HCN always results in mixtures of cis/trans-isomers, the stereoselective HNL-catalyzed addition is of great advantage in the synthesis of natural products. The syntheses of the natural monoterpenes cis-p-menth-8-ene-l,7-diol and cA-/ -menthane-l,7,8-triol are interesting examples for the application of this methodology (Scheme 9). ... 

In the laboratory of P. Kocovsky, novel pyridine-type P,A/-ligands were prepared from various monoterpenes. The key step was the Krohnke pyridine synthesis, and the chirality was introduced by the a,(3-unsaturated ketone component, which was derived from enantiopure monoterpenes. One of these ligands was synthesized from (+)-pinocarvone which was condensed with the acylmethylpyridinium salt under standard conditions to give good yield of the trisubstituted pyridine product. The benzylic position of this compound was deprotonated with butyllithium, and upon addition of methyl iodide the stereoselective methylation was achieved. The subsequent nucleophilic aromatic substitution (Sw/ r) gave rise to the desired ligand. 

Monosubstituted norbornenones may also be used as precursors for stereoselective rearrangements provided that the 7-substituent has a syn orientation to the carbonyl group. For example, dimethyl acetal 40 is used in the total synthesis of the iridoid monoterpene ( + )-dimethyl secologanoside 0-methyl ether (43)1068 as well as the synthesis of the civ-fused hydrindanone 471069. 

In this article the stereoselective syntheses of methylcyclopentanoid monoterpenes are reviewed. The chemical procedures performed for the synthesis of glycosidic and non glycosidic iridoids will be presented. 

The synthesis of modular pyridine-type /)1V-Iigands from monoterpenes is described (eq 45). An cr-picolyl-type lithiation with BuLi followed by a stereoselective methylation using Mel gives new /)1V-Iigands. ... 

S. Fuchs, Th. Beck, S. Burkardt, M. Sandvoss, and A. Mosandl, Biogenetic studies in Mentha x piperita. 1. Deuterium-labeled monoterpene ketones Synthesis and stereoselective analysis, J. Agiic. Food Chem. 47 3053 (1999). 

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