Quantitative addition of organolithium and Grignard reagents to camphor (1) and fenchone (2) proceeds via precomplexation of the ketone with CeCl3 at room temperature. Excellent addition using catalytic or substoichiometric amounts of CeCl3 is demonstrated for the first time.

The new optically active 1,3-diols 5-8 with (1R)-(+)-camphor and (1R)-(-)-fenchone skeleton were synthesized in high yields from the homoallylic alcohols 1-4 using a very effective ozonolysis followed by reduction. The absolute configuration of (1R, 2S, 12R)-6a was determined by a single crystal X-ray study.

The aldehyde 3, prepared by ozonolysis of 2-allyl-2-nitrocyclododecanone, gave the ring-enlargement product 5 (85%) by treatment with (i-Bu)(2)AlH. Its transformation to the tetradecano-14-lactone (8) via the aldol ester 6 and other routes (best is reduction with Bu(3)SnH, AIBN, toluene) was difficult. Remarkable is the smooth denitrification of 3 (loss of HN0(2)) to the conjugated dione 4 by chromatography on silica gel or base treatment.

An improved strategy for synthesis of 1-chloro-bicyclo[2.2.2]octane is described in which the key compounds 1-norbornyl substituted ethyl formate (3) or 1-norbornylcarbaldehyde (7) were prepared from 1-norbornyllithium (1). The latter appeared as a useful precursor for the synthesis of various organic bridgehead substituted derivatives.

The new chiral nonracemic homoallylic exo-alcohols 6, 7, 10 with (1R)(+)-camphor (1) and endo-alcohols 8, 9, 11 with (1R)-(-)-fenchone (2) skeleton were synthesized in high yields by the stereoselective addition of allyl and substituted allylic Grignard reagents 3-5 to 1 and 2, respectively. The addition of the 2-butenyl (crotyl) reagent 5 occurred with high selectivity leading exclusively to alpha-methylallyl alcohol 10 with ketone 1 and to (Z)-2-butenyl alcohol 11 with ketone 2. The absolute configurations of the homoallylic alcohols 6-11 were determined by NMR methods.

The activity and efficiency of anhydrous CeCl3 depend strongly on the drying procedure. Deactivation of CeCl3 occurs during the drying process as a result of hydrolysis by the hydrate water, when heating above 90 degrees C. The highly active CeCl3, prepared by an improved drying procedure, is demonstrated to activate rapidly (in catalytic and stoichiometric amounts) ketones at room temperature, providing excellent addition of organometallic reagents. Copyright (C) 1996 Elsevier Science Ltd