Flow injection mass spectrometry analysis (FIA-MS) has been used extensively in reaction monitoring and optimization due to its simplicity and easy of use. Detection of enantiomers in stereospecific reactions has been reported. Reetz et al.  prepared isotopically labeled pseudoenantiomers and pseu-doprochiral compounds that behave chemically as a racemate or as a meso compound. Kinetic resolution of a racemate gives two products with different molecular weights, which enables the ratio to be determined with mass spectrometry. The authors used FIA-MS with a microplate autosampler to allow analysis of up to 1000 reactions/day. Guo et al.  reported an alternative mass-tagging approach to the measurement of enantiomeric excess by FIA-MS. In their method, an equimolar mixture of pseudoenantiomeric mass-tagged pairs of reagents was prepared that differ in a substituent remote to the chiral center. Szewczyk et al. developed a quantitative method to monitor the progress of the tagging experiment and to optimize the reaction by conversion of the product ketones into ESI-active derivatives . The method was used to monitor three experiments involving 33 different substrates with more than 170 determinations of yield. McKeown et al. incorporated mass spectrometry-sensitive linkers into the synthesis of combinatorial libraries . Upon photochemical cleavage after synthesis, these linkers can be monitored by high throughput FIA-MS to provide information about the yield of the synthesis and the photocleavage processes. A similar strategy that incorporates analytical constructs into the library synthesis for analysis and quality control was used by Lorthioir et al. . These researchers selected an analytical fragment that is highly sensitive in ESI-MS for this purpose. The usefulness of the method was demonstrated by assessment of synthesis of library compounds that are otherwise not detected in ESI-MS analysis due to low sensitivity. Congreve and Jamieson have recently reviewed strategies with high throughput analytical techniques for reaction optimization .
In library synthesis that involves a solid-state polymer-bead support, matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and secondary ion mass spectrometry (SIMS) have been used to monitor products of reaction either through direct analysis of bead-bound compounds or in situ analysis of the compounds after cleavage. These approaches have been reviewed extensively in the literature [5-20]. A recent development in the use of MALDI-TOF and SIMS in reaction monitoring and optimization was reported by Enjalbal et al. 
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