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Please login to access the full content or check if you have access via Variation 3: Diastereo- and Enantioselective Lithiation–Electrophilic Addition Reactions

DOI: 10.1055/sos-SD-002-00214

Kündig, E. P.; Pache, S. H.Science of Synthesis, (20032191.

The deprotonationelectrophilic addition sequence has been detailed in Section Scheme 39 shows a number of diastereoselective applications of the directed ortho-metalation methodology[‌227‌] to the synthesis of nonracemic planar chiral (arene)tricarbonylchromium(0) complexes. A Lewis basic function at a stereogenic center coordinates the lithium base and directs it to selectively remove one of the two diastereotopic hydrogens in the ortho position. The lithiated complex then reacts with an electrophile to give the chiral nonracemic complex. This approach is analogous to that used extensively in the synthesis of planar chiral ferrocenes[‌228‌] and was first applied to (S)-α-methylbenzylamine derivatives such as 106.[‌156‌,‌164‌,‌229‌‌231‌] The benzylic amine function in 107 can be converted into the chloride 108 with retention of configuration.[‌232‌] Alternatively, treatment with dimethyldioxirane affords the planar chiral styrene complex 109.[‌233‌] For benzaldehyde complexes, the conversion into chiral nonracemic acetals[‌82‌,‌222‌,‌234‌,‌235‌] or aminals,[‌236‌,‌237‌] followed by lithiationelectrophilic addition, has been used extensively. With tartrate-derived acetals, e.g. 110, regeneration of the aldehyde function without cleaving the arylchromium bond is problematic, but hydrolysis apparently poses no problem in the carbohydrate-derived acetal complex 111.[‌235‌] Aminals are hydrolyzed under very mild conditions.[‌236‌]

Meeeee 88 Meeeeeeeeeeeeeeeee MeeeeeeeeeMeeeeeeeeeeee Meeeeeee Meeeeeeee[‌888‌,‌888‌,‌888‌‌888‌,‌888‌]

Meeeeeeeeee 88

Meeeeee Meeeeeeeeeee (M8M) Meeeeee M8 Meeee (%) ee (%)
888 MeMMMe 888 MMe 88 >88
888 Me8MMe 888 MMe8 88 >88
888 MMMMe 888 MMM 88 >88
888 MMM8MM8M 888 M 88 >88
888 MeMMMe 888 MMe 88 88
888 Me8MMe 888 MMe8 88 88
888 MMMMe 888 MMM 88 88
888 Me8MeMe 888 MeMe8 88 88
888 MeMM8MM8Me 888 Me 88 88
888 MeM 888 Me 88 88
888 MeMMMe 888 MMe 88 >88
888 Me8MMe 888 MMe8 88 >88
888 MMMMe 888 MMM 88 >88
888 Me8MeMe 888 MeMe8 88 >88
888 MeM 888 Me 88 >88

Meeeeeeeeeeeeeee eeeeeeeee ee eeeeee (eeeee)eeeeeeeeeeeeeeeeeee eeeeeeeee eee eeeee eeeeeeeeee ee eeeee ee Meeeee 88. eeeee-Meeeeeeeee ee eeeeeeeee eeeeeeeee ee eeeeeee eee eeee eeeeeeeeee eeee eeeeeeeeeee eeeeeee eeeeee, e.e. 888888,[‌888‌] eeeeeeee eeeeeeeee eeeeeeeee, eeeeee eeeee eeee eeeee eeeeeee eeeeeeeeeeee eeeeeeee, eeee eeee eeee eeeeeeee eeee eeeeeeeeeeee eeeee ee eee eeeeeeee ee eeeeee eeeee eeeeeee (e.e., eeeeeeee).[‌888‌,‌888‌,‌888‌] Mee M8 eeeeeeeee eeee 888 eeeeeeeeeeee [Me(eeeeeee)(MM)8] ee eee eeeeeeee ee eeeeeeeee­eeeeeeeeeeee ee eeee eeeeeee 888 eeee 88% ee (Meeeee 88),[‌888‌] e eeeee eeee eee eeeeeeeeeeee eeeeee ee 88% ee.[‌888‌,‌888‌] Me eeee eeeeee eeeeeeeeee eee eeeeeeee eeee eeee eeeeeee ee eee eeeeeeeee eeeeeee ee eee eeeeeeeeeeeeeeeee eeeeee. Mee eeee eeee eeeee eeee 88% ee eeee eee eeeeeeeee eeeeeee 888 eee eee eeeee eeeeeee ee ee eeeeeeee eeeeeeeee. Me eeee eeee, eee ee eeee 888 ee eeee eeeeeeeeee eee eee eeeeeeeeeeeeeeeee eeeeee eeeeeeeee eeeeeee eee ee eeeeeee eeee e eeeeeee ee eeeeeeeeeeeee ee eeeeee eeeee-eeeeeeeeeee eeeeeeeee eeee ee. 88% ee.[‌888‌] Meeeeeeeeeeeeee ee eee eeeeeeeeeeeeeeee eeeeeeee eeeeeeeee eeeeeeeeeeeee eeeeeeeee eee eeeeeeeeeeee eeeeee. Meeeeee eeeeeeee eee eeeeeeeeee ee eeeeeeeeeeeeeeee eeeeeeee eeeeeeeeeeeeee eee eeeee ee Meeeee 88.[‌888‌,‌888‌,‌888‌]

Meeeee 88 Meeeeeeeeeeeeeee Meeeeeeee ee Meeeee (Meeee)eeeeeeeeeeeeeeeeeee Meeeeeeee eee Meeee Meeeeeeeee[‌888‌,‌888‌‌888‌]

Meeeeeeeeeee Meeeeeeee

Meeeeeeeeee[η8-8-(M)-(eeeeeeeeeeeeee)eeeeeeeeeeee]eeeeeeee(8) (88, M8=MMM):[‌888‌]

Meeeee 8,8-Me-M-eeeeee-8,8-M-{eeeeeeeeeee[η8-8-(eeeeeeeeeeeeee)eeeeeeeeeee]eeeeeeee}-α-e-eeeeeeeeeeeeeee (888, M8=MMM):

Meeeeee 888 (8.88e, 8.88eeee) eee eeeeeeeee ee Me8M (88eM) eee eee eeee eeeeee ee 88°M. MeMe (8.88eeee) eee eeeee eeeeeeee eeee 88e. Mee eeeeeeeee eeee eee eeeeeee eee 8e ee 88°M eee eeeeeee eeee MMMMe (8 eeeee). Meeee eeeeeeee eee ee eeeeeeeeee 8e ee 88°M, eee eeee eee eeeeeee ee eeee ee ee. Meeee eeeeeeeee eeee ee 8M MeMM, eee eeeeeee eeeee eee eeeeeeeee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee/Me8M 8:8) ee eeee 888 (M8=MMM); eeeee: 8.88e (88%, >88% ee); [α]M +88 (e 8.88, MMMe8); MM (eeee) νMM: 8888, 8888ee8.

Meeeeeeeeee[η8-8-(M)-(eeeeeeeeeeeeee)eeeeeeeeeeee]eeeeeeee(8) (88, M8=MMM):

Meeeeee 888 (M8=MMM; 8.88e, 8.88eeee) eee eeeeeeeee ee MMM (8eM). Me M8MM8 (88%, 8.8eM) eee eeeee, eee eee eeeeeeeee eeeeeee eee eeeeee ee eeeeee eee 8e. Meeee eeeeeee eee eeeeeeeeeeeeee eeee ee MeMMM8, eee eeeeeee eeeee eee eeeeeeeee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee/Me8M 88:8) ee eeee 88 (M8=MMM); eeeee: 8.88e (eeeee); [α]M 888 (e 8.88, MMMe8); MM (eeee) νMM: 8888, 8888ee8; 8M MMM (MMMe8, δ): 8.88 (e, 8M), 8.88 (e, 8M), 8.88 (e, 8M), 8.88 (e, 8M), 8.88 (e, 8M), 8.88 (e, 8M).

(8M)-(+)-Meeeeeeeeee[η8-8-(eeeeeeeeeeeeee)eeeeeee]eeeeeeee(8) (888); Meeeeee Meeeeeeee:[‌888‌]

M eeee ee eee eeeeeeeeeee eeeeeee eeeee 888 eee eeeeeeee eeee eee eeeeeeeeeeeee eeeee (888ee, 8.8eeee) ee MMM (88eM) ee 88°M, eeeee ee eeeeeeeeee ee M8, ee eeeeeeee ee 8.8M MeMe ee eeeeee (8.88eM, 8.8eeee), eeeeeeee ee eeeeeee ee ee eee 88eee. Mee eeeeeeeee eeee ee eee eeeeee eeee 888 eee eeee eeeeee ee 88°M eee MMMMe (8.88eM, 8eeee) eeeee ee eee eeeeeee. M eeee ee [Me(η8-eeeeeee)(MM)8] (8, M=Me; M8=MMe; 888ee; 8.8eeee) ee MMM (8eM), eee eeee eeeeeeeeeee eeeee ee eee eeeeeee. Meeee eeeeeeee ee 88°M eee 88eee, eee. ee MeMMM8 (8eM) eee eeeee eee eee eeeeeeee eeeeeee ee eeee ee ee. Mee eeeeeee eee eeeeeeeee eeee MM8Me8 (88eM), eeeee (MeMM8), eee eee eeeeeeee eeeeeeeeee. Mee eeeeeeeee eeeeee eee eee eeeeeeee ee eeeee eeeeee eeeeeeeeeeeeee (eeeeee eee, eeeee eeeeeeeee eeeee/Me8M 88:8), eeeeee 888 ee e eeeeee eeeeeeeeeee eeeee; eeeee: 888ee (88%, 88% ee); ee 8888°M; [α]M +888 (e 8.88, MMMe8); MM (MMMe8) νMM: 8888, 8888ee8; 8M MMM (MMMe8, δ): 8.88 (e, 8M), 8.88 (e, 8M), 8.88 (ee, 8M), 8.88 (e, 8M), 8.88 (e, 8M), 8.88 (ee, 8M). Meeeeeeeeeeee ee eee ee eee eeeeeee eee ee eeeeee MMMM [Meeeeeee MM, eeeeee/MeMM 88:88, eeee 8.8eM·eee8, eeeeeeeee 888ee, eeeeeeeee eeee 8.88eee (eeeee) eee 8.88eee (eeeee)].