Diastereoselective Lithiation of N-Benzyl Pyrroloimidazolones Derived from l-Proline Hydantoin

Abstract

An N-benzyl pyrroloimidazolone derived from l-proline hydantoin undergoes asymmetric lithiation with n-BuLi/TMEDA in toluene to give products of electrophile quench (E+) that range from 87:13 to 91:9 diastereomeric ratio (dr). All products appear to have the same relative stereochemistry as determined by transmetalation of benzylic stannanes, which gave identical major diastereomers for several products as to what was observed by direct lithiation–substitution of the starting material. X-Ray crystallography of the major diastereomer of the benzophenone adduct established (R)-configuration at the benzylic center, i.e., anti stereochemistry with respect to the imidazolone. Lithiation of a selectively deuterated analogue of the starting material according to the optimized conditions, followed by benzophenone quench, gave diastereomeric products with far lower selectivity (53:47 dr) than lithiation of the non-deuterated analogue (91:9 dr) owing to a large primary kinetic isotope effect. These preliminary results imply that metalation of the N-benzyl pyrroloimidazolone may follow an asymmetric deprotonation pathway to give a benzylic carbanion that retains its configuration during electrophile quench.

Stereoselective Synthesis of N‐Propargyl Alkynes and Axial Chiral N‐Allenes with Epimeric Pyrroloimidazolone Auxiliaries

“…The required pyrroloimidazolone syn-10 was synthesized by modification of the procedure used to make the N-benzyl analogue previously. [13] Thus, deprotonation of L-proline hydantoin 14 with NaH in DMF and subsequent treatment with trimethylsilyl propargyl bromide [14] gave hydantoin 15 (Scheme 2). Hydrosilylation of 15 with Schwartz's reagent (Cp 2 ZrHCl) in THF followed by addition of chlorotriethylsilane (TESCl) afforded syn-10 as a single diastereomer in 79% yield.…”

“…asc.wiley-vch.de deuterated solvent for 13 C spectra according to published values. FT-IR spectra were obtained on Bruker ALPHA platinum ATR spectrometer as neat materials.…”

“…Second, the extent to which transmetalation of lithiated intermediates is required or affects the outcome of reactions using syn-10 or anti-10. Third, the ability to alter the configuration of the products (11,13) by using epimeric starting materials syn-10 or anti-10. These auxiliaries have been used previously to induce planar chirality in ferrocenes [11] and η 6 -arene Cr (CO) 3 complexes, [12] and for chiral induction at benzylic positions.…”

“…These auxiliaries have been used previously to induce planar chirality in ferrocenes [11] and η 6 -arene Cr (CO) 3 complexes, [12] and for chiral induction at benzylic positions. [13] Their epimeric forms typically result in reversal of the sense of diastereo-induction despite the fact that both auxiliaries are derived from L-proline.…”

“…Third, the ability to alter the configuration of the products ( 11 , 13 ) by using epimeric starting materials syn ‐ 10 or anti ‐ 10 . These auxiliaries have been used previously to induce planar chirality in ferrocenes and η 6 ‐arene Cr(CO) 3 complexes, and for chiral induction at benzylic positions . Their epimeric forms typically result in reversal of the sense of diastereo‐induction despite the fact that both auxiliaries are derived from L‐proline.…”