Fluorous quasi-racemic synthesis

A similar approach of fluorous quasi-racemic synthesis [20] was used to synthesize both enantiomers of mappicine at the same time in a coded mixture. The pyridine derivative 41 was split, and the carbonyl group was reduced enantioselectively by (+)- and (-)-DIP-Cl, respectively. The resulting enantiomerically pure alcohols were subsequently derivatized - the (1 ) enantiomer with BrSi(iPr)2CH2CH2QFi3 to yield (Ji)-4-2 and the (S) enantiomer with BrSi(iPr)2CH2CH2CgFi7 to yield the quasi-enantiomer (S)-43. The mixture of both quasi-enantiomers was then subjected to the reaction sequence leading to the fluorous mappicines (R)-44 and (S)-4S. These were separated by fluorous chromatography and deprotected to yield the two mappicine enantiomers (Scheme 3.21). 

Scheme 3.21 Fluorous quasi-racemic synthesis of both enantiomers of mappicine [20], (DIP = diisopinocampheylborane Rp is either QFn or CgFiy).

Enantiopure or enantioenriched compounds can be obtained by asymmetric synthesis or by separation of a racemic reaction mixture. Quasi-racemic FMS provides a new approach to enantiomeric compounds (see Scheme 13.2) [26, 27]. Quasi-racemic synthesis starts with two individual R- and 5-enantiomers attached to two different fluorous tags. After steps of mixture synthesis followed by F-HPLC demixing and detagging, two individual products as enantiomers are obtained (see Sections 13.2.1 and 13.2.2). The separation and identification of the final quasi-enantiomers are ensured by the phase-tag-based F-HPLC. In a more complicated quasi-racemic FMS, additional enantiomerically pure building blocks and fluorous tags can be used to generate more chiral centers and more than two products as stereoisomers (see Sections 13.2.3 to 13.2.8). 

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