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Abstract
In the course of the experimental work, more than 50, structurally diverse monoterpene-based enantiopure aminodiols, alicyclic-condensed heterocycles and β-amino acid derivatives were prepared and characterized.
Functionalization of the enantiomeric monoterpenes (11, 60, 140 and 151) was achieved by applying simple synthetic steps, including stereoselective transformations.
The optical purity of (1S)-(+)-3-carene 60 remained intact in further reactions; the formation of the new asymmetric centers was controlled by stereoselective steps. Novel, optically active epoxy alcohol 111 was subjected to a stereoselective epoxide ring-opening procedure, resulting in variously substituted aminodiols. Carane-based aminodiols 114-123were prepared with moderate to good overall yields.
Transformation of readily available (1R)-(-)-myrtenol 11 by well-known methods resulted in enantiopure key intermediate 127 in good yield, a corresponding precursor for optically active pinane-based aminodiols 128-133 and 135-137. Analogously, pinane-based aminodiol 142, an enantiomer of 132, was successfully prepared by using a similar synthetic protocol to that for 132.
The ringclosure of pinane- and carane-based aminodiols proved to be highly regioselective, furnishing exclusively carane-fused 1,3-oxazines 144-148 and pinane-fused oxazolidines 134 and 150. Formation of regioisomer carane-based spiroderivative 143 or pinane-based six-membered heterocycle 149was not observed.
Simple synthetic procedures for the synthesis of enantiomerically pure pinane-based β-lactams 152 and Boc-protected 153 involved regio- and stereoselective CSI addition to enantiopure apopinene 151. The optically active β-amino amides and 1,3-diamines were derived from 152 and 153. The consecutive lactam-opening procedure and tosylation reaction furnished amino amides 161, 163 and 167-177. By subsequent reduction, only diamines bearing a tertiary amino function (160, 162, 164 and 178-182) could be synthetized, and hence a series of variously substituted β-amino acid derivatives were prepared.
The optically active monoterpene-based tri- and bidentate ligands and monoterpene-condensed heterocycles were applied as catalysts in the asymmetric addition of Et2Zn to benzaldehyde. The general applicability of the catalysts and the influence of structural factors on the catalytic activity were studied.
Carane-based tridentate catalysts 114-123 exerted low enantioinduction in the asymmetric addition of Et2Zn to benzaldehyde, affording the R or the S enantiomer of 1-phenyl-1-propanol 55. A moderate ee value (ee = 37%) was achieved by utilizing N-(S)-1-phenylethyl derivative 120.
In comparison, improved catalytic activity was observed with pinane-based tridentate ligands 128-133 and 135-137, yielding (R)-55. N-Benzyl aminodiol 132 furnished the best ee value (ee = 61%) in the test reaction. The quantum chemical molecular modeling studies performed correlated well with our experimental findings. Increasing enantioinduction was observed in sequence NH2 < NRR < NHR. The catalytic activity of enantiomer 142 was weaker (ee = 39%) yielding (S)-55.
