Menthol groups, diastereoselective reactions

Michael addition to (+)-pu]egone [( + )-12] is not only possible with carbon nucleophiles, but also nitrogen and sulfur compounds. Thus, reaction of (+)-pulegone with benzylamine, followed by reduction of the carbonyl group with sodium borohydride, gives (1 / .3/ ,4,S )-8-(ben-zylamino)menthol (24)28, used for the formation of chiral 1.3-oxazines which react with Grignard reagents diastereoselectively (Section D. 1.3.1.4.). 

The chiral alcohols are mainly employed as esters or enol ethers. Esters with carboxylic acids can be obtained by any convenient esterification technique. Dienol ethers were obtained by transetherification with the ethyl enol ether of a 1,3-diketone, followed by Wittig reaction8 silyldienol ethers were obtained by the method of Danishefsky11-12 and simple enol ethers by mercury-catalyzed transetherification13. Esters and enol ethers have been used as chiral dienophiles or dienes in diastereoselective Diels-Alder reactions (Section D. 1.6.1.1.1.1.). (R)-l-Phenylethanol [(R)-4] has been used for enantioselective protonation (Section C.) and the (S)-enantiomer as chiral leaving group in phenol ethers for the synthesis of binaphthols (Section B.2.) the phenol ethers are prepared as described for menthol in the preceding section. (S)-2-Octanol [(S)-2] has found applications in the synthesis of chiral allenes (Section B.I.). 

Somewhat between diastereoselective and enantioselective approaches is the Cram s synthesis involving the oxazolines with chiral alkoxide leaving groups [26]. In this manner, bromine in oxazoline 596 was substituted with sodium alkoxides, derived from readily available natural alcohols such as menthol (597), fenchyl alcohol (598), bomeol (599), quinine (600), and quinidine (601) to give the respective chiral oxazolines 602-606, Scheme 10. The Meyers reaction of oxazolines 602-606 and 1-naphthylmagnesium bromide (608) was effected at low temperatures (-42 °C) affording the expected biaryl 609 with respective chiral induction. 

With this new methodology in hands, Hu et al. [166] explored the trapping of the 1,4-addition intermediate with a different electrophile for the development of a new MCR. RhjCOAc) was again the most active catalyst in the 1,4-addition/aldol-type intramolecular cascade reaction. Under the optimized reaction conditions, this three-component reaction worked well with a broad family of bifunctional substrates 135 bearing different substituents on the aryl group next to the enone moiety and a variety of alcohols 136 (Scheme 3.63). In all cases, 1-indanols 137 were obtained in 60-83% yield and with complete diastereoselectivity. Enantiopure 1-indanol was obtained employing a L-menthol-derived diazo compound. The intermolecular four-component version was also attempted, but the formation of the desired product was not observed. 

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