Mono and di-substituted alkyl and aryl quinoxalines are rapidly reduced in high yield to their respective 1,2,3,4-tetrahydro-derivatives by borane in THF solution. In the case of the 2,3-di-substituted compounds, reduction is stereoselective yielding exclusively the cis-isomers. Sodium borohydride in acetic acid also reduces alkyl and aryl quinoxalines, but proceeds with lower yields and often produces side products. Sodium borohydride in ethanol reduces quinoxaline and 2-methylquinoxaline in high yield; however, the reaction is very slow, whereas 2,3-dialkyl and 2-aryl quinoxalines are not efficiently reduced by sodium borohydride in ethanol. [3]. One approach to obtaining these compounds is direct reduction of the parent quinoxalines. Classical reagents for the conversion of quinoxalines to 1,2,3,4-tetrahydroquinoxalines include lithium aluminum hydride [4] and catalytic hydrogenation [4,5]. Both methods proceed with moderate to good yields but require substantial purification procedures and extended reaction times. In fact, we found a significant amount of starting quinoxaline unconsumed by LAH even after increasing the stipulated reaction time to six to twelve hours. More recently, the use of titanium chloride [6] or indium powder [7], yields mixtures of stereoisomers and offer no experimental improvement. We were considerably more intrigued by sporadic reports over the last three decades that featured the use of various boron reagents for the reduction of the diazine ring in the quinoxaline system. However, results from these prior studies were somewhat difficult to interpret. For example, pyridine-borane in acetic acid solution at room temperature after seven hours was shown to reduce 1a in 95% yield, while trimethylamine-borane was apparently ineffective [8]. Subsequently, 2-aminopyrimidine-borane was used for this same transformation [9] but the reported yield was only 54%. Use of the borohydride ion has a similar history. In 1973, Rao stated [10] that quinoxaline was unaffected by sodium borohydride in methanol, but showed that this reagent in acetic acid reduced quinoxalines in moderate to good yields, in the presence of an electron-withdrawing substituent on the fused benzene ring. Later papers demonstrated that both potassium borohydride in carboxylic acid media [11] and sodium cyanoborohydride with benzyl chloroformate in methanol [12] effectively reduced 1a but were accompanied by, respectively, alkyaltion or acylation at nitrogen.We report herein that borane in THF rapidly converts 1a-f to 2a-f (Scheme 1). As demonstrated in Table I, the reactions proceed in excellent yields and the reductions involving 1c and 1f are highly stereoselective, resulting in the syn addition of hydrogen to give 2c and 2f. We also examined sodium borohydride as a reducing agent for 1a-f and are now able to clarify prior ambiguities. In ethanol, sodium borohydride slowly reduces 1a and 1b to give excellent yields of 2a and 2b. In addition, we have extended the procedure of Rao [10] by using sodium borohydride in acetic a...
