The utility of lithium and potassium tri-sec-butylborohydrides (Land K-Selectrides) and lithium triethylborohydride as reagents for the conjugate reduction and reductive alkylation of unsaturated ketones and esters is surveyed. In general, /3-unsubstituted cyclohex-2-en-l-ones undergo exclusive 1,4 reduction to ketone enolates which can be protonated or alkylated in high yield. Efforts to achieve with this method the reduction of ,/3-enoates to ester enolates are described, culminating in the first synthetic methodology which generally accomplishes this transformation. Many examples are presented and the dependence on various reaction parameters including solvent, temperature, nature of borohydride, and ester type is explored. The resulting ester enolates exhibit the same reactivity as those prepared by direct metalation of saturated esters, particularly with regard to alkylation, ,/3-, dienoic esters were found to be very resistant to conjugate reduction, and -acetylenic esters furnish only propargylic alcohols in good yield. A series of competition experiments between various carbonyl-containing substances is also reported which defines some relative rates of reduction.

An extensive series of 3-(1-indolinyl)benzylamines and related compounds was synthesized and tested for analgesic activity. After a detailed study of structure-activity relationships, 3-(1-indolinyl)benzylamine (2b) was selected for further investigation as the most interesting member of this novel class of compounds. It was active in both the phenylquinone writhing and tail-flick assays for analgesic activity. No motor deficits were observed in the rotorod test, and 2b was found to be free of any other effects on the central nervous system. The compound did not bind to opiate receptors, since it was inactive in inhibiting the stereospecific binding of [3H]naloxone in rat brain homogenates. Thus, 3-(1-indolinyl)benzylamine represents a novel analgesic with an unusual chemical structure and biological profile.

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In a program to discover histidine decarboxylase inhibitors, histidine derivative V was found to have analgesic properties in a number of our animal models. Subsequently, we synthesized the oxygenated analogues 2 and 3. The syntheses of these compounds, reported here, led

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