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Enantiomerically pure diarylmethylamines are important intermediates in the synthesis of biologically active compounds. [1] Cetirizine hydrochloride (1) stands out from several drug candidates as a commercially important nonsedating antihistamine agent. Binding studies indicate that the R enantiomer displays a better pharmacological profile than the racemate. [2] Despite the importance of enantiopure diarylmethylamines, synthetic accesses and especially asymmetric (catalytic) processes for their synthesis are rather limited. [3] While there are several synthetic routes to, for example, enantiopure cetirizine that utilize resolution techniques, [4] stoichiometric amounts of chromium complexes, [5] or diastereoselective approaches with chiral auxiliaries, [6] to the best of our knowledge there is only a single report on an asymmetric catalytic addition of an organometallic arylation agent to an imine derivative. Hayashi and Ishigedani described a highly enantioselective rhodium-catalyzed process for the arylation of N-sulfonylimines with aryl stannanes (up to 96 % ee). [7] For quite some time we have been engaged in the asymmetric transfer of a phenyl group from organozinc reagents and have developed a protocol for the highly enantioselective transfer of a phenyl group to aldehydes using ferrocene (R p ,S)-2 and cyrhetrene (R p ,S)-3. [8] However, a major difficulty in the development of asymmetric processes for the transfer of a phenyl group remains the much higher reactivity of diphenylzinc relative to dialkylzinc and the concomitant rapid uncatalyzed background reaction.Recently, we developed a catalytic procedure for the enantioselective addition of diethylzinc to masked N-formylimines by employing catalytic amounts of [2.2]paracyclophane-based ketimines. [9,10] We now report on the combination of both methods, which leads to the first highly enantioselective addition of phenylzinc to imines and gives rise to optically active diarylmethylamines in very high enantiomeric excesses.At the outset of our study we examined the use of different N,O-ligands (Scheme 1) in the phenylation of N-[p-tolylmethyl-(toluene-4-sulfonyl)]formamide (7 a, Table 1). This class of N-acylimine precursors is readily available in a one-pot synthesis from benzaldehyde, amide, and p-tolylsulfinic acid. [11] The addition to the imine then proceeds by deprotonation of amide 7 a, followed by elimination of the sulfinate to form N-formylimine 8 a. Addition of the zinc reagent gives rise to the N-formylamine 9 a. We started out by employing the reaction conditions developed for the enantioselective transfer of a phenyl group to aldehydes using a mixed zinc reagent formed in situ from diphenylzinc and diethylzinc. This reagent selectively transfers only the phenyl moiety to the substrate to afford N-formylamine 9 a in very high yield without formation of the corresponding ethylation product. [12] The ligand screening (Table 1) showed that ferrocene (R p ,S)-2 and cyrhetrene 3, which represent the best ligands for the enantioselective transfe...

Small amounts of simple methoxy poly(ethylene glycol)s (MPEGs) have a beneficial effect on catalyzed asymmetric aryl and alkyl transfer reactions onto aldehydes. The enantiomeric excesses of the products are improved, and this "MPEG effect" allows a reduction of the catalyst loading by a factor of 10.