Science of Synthesis

Eckhardt, M., Science of Synthesis, (2007) 25, 489.

2-Metalated homo or mixed heteroatom acetals of formaldehyde are useful formyl anion equivalents. The first synthetically valuable compound of this type, 1,3-dithian-2-yllithium, provides the platform for the subsequent development of chiral variants that permit diastereoselective additions to both aldehydes and ketones.[‌99‌,‌100‌] A modern formyl anion equivalent should combine a convenient access, mild and selective removal of the mask to liberate the aldehyde group, high asymmetric induction in the addition process (preferably in the sense of “reagent control”), and easy separation of possibly resulting diastereomers. Among the available reagents, 4-isopropyl-3-[(methylsulfanyl)methyl]-5,5-diphenyloxazolidin-2-one (‌56‌) in an enantiomerically pure form seems to fulfill these criteria best;[‌101‌–‌105‌] this auxiliary and its enantiomer are easily obtained from the commercially available enantiomers of 4-isopropyl-5,5-diphenyloxazolidin-2-one (‌55‌) via (methylsulfanyl)methylation (see ‌Scheme 23‌). The oxazolidinone (S)-‌56‌ can be efficiently deprotonated at the N,S-acetal carbon atom to generate the lithiated derivative ‌57‌. The lithiation step is best carried out with butyllithium in tetrahydrofuran at −78°C, and the lithiated species is then reacted with the aldehyde at −100°C to achieve the maximum yield and diastereoselectivity of the desired product ‌58‌.

Meeeee eee eeeeeeeee, α,β-eeeeeeeeeee, eee eeeeeeee eeeeeeeee eee eeeeeeeeee eeee, eeeee eeeeeeeeeeeeeeeeeeee eeeeeeeee eeee eeee eee eeeeeeee eeeeeeeee ee eeeeeeee eee eeeeeeeee eeeeeeeee. Meee eee eeeeeeeeeeeee, ‌88M‌ eee ‌88M‌, ee eee eeee eeeeeeee eee eeeeee. Me eeeeeeeee ee eeee eeeeeeeee ee eee eeee eeeeeeeeee ee eeee eeeeeeeeeeeee ee eeeeeeeeeeeeee ee eeeeeeeeeeeeeeeee. Mee eeeeee ee eeeeee eeee eeeeeeeeee eeeeee eeee eee eeeeee ee eeeeee eeeee eeeeeeeeee eee eee eeeee ee eeeeeeeeeeee eeeeeeee eee eeeeeee. Meee eeee eeeeeee eee eeeeeeee eeeeeeeeee eee eee eeeeeeee eee eeeee, eeeee eeeeeee ee eee eeeeeeee eeeee, eeeeee ee 8-eeeeeeeeeeeeeeee eeee e eeeeeeeeeee eeeeee eeeeeeeeeeee.[‌888‌]

‌Meeeee 88‌ Meeeeeeeeeeeeeeeee Meeeeeeee ee ee Meeeeeeeeee Meeeee ee Meeeeeeee[‌888‌]

‌Meeeeeeeeee 88‌

Mee eeeeeeeeeeeeee ee eee eeeeeeeeeeee M,M-eeeeee ee eee eeeeeeeeeeee eeeeeeee ee eeee eeeeeeeee eeeee eee 8-eeeeeee eeeee eee eeee eeeeeeeee. Me ee eeeeeeeeeeee, eee eeeeeeeeeeee eeeeee ‌88M‌ (M8 = Me, eee ‌Meeeee 88‌), eeeeee eeee eee eeeeeeeeeeeee (M)-‌88‌ ee eeeeeeeee eeee eeeeeeeeeeee eee eeee eeeeeeeeeeee, ee eeeeeee ee eee eeee eee eeee eeeeeeeeeeee eeeeee eeeee ee eeeeee eee eeeee eeeeee ‌88‌ eeee eeeeeeeee eeeeeeeeeeeeeeeeeeee (‌Meeeee 88‌;[‌888‌] eeee: eee eee eeeeeeeeee eee eeeeeeeeee eeeeee eee ee eeeeeeee ee eeee eee-eee eeeeeeeee eee e eeeeeeee eeeeeeeeee eeee eee ee eeeeeeee). Mee eee eeeeeeeeeeeee-eeeeeeeee eeeeeeeeeeee eeeeee ‌88‌, eeeeeee ee eee eeeeeeee eeeee ee eeee eee 8-eeeeeeeeeee ‌88‌ ee eeeeeeeeeeee ee eeeeeeeeee eeee eeeeeee(MM) eeeeeeeeeeeeeeee ee e eeeeeee ee eeeeeeeeeeee, eeeeeeeeeeeeeee, eee eeeee ee eeee eeeeeeeeeee, eeeeeeee ee eeeeeeeee ee eee eeeeeeeeeeee eeeeeeeeee ‌88‌ eeee 8,8-eeeeeeeeeeee[8.8.8]eeeee-8-eee.[‌888‌] Meeeeee, eeeee eee eeeeeeeeee ‌88‌ ee eeeeee ee eee eeeeeeee ee eeeeeeeeeeeee ee eeeeeeeeeeeeeeeeeeeee, eee eeeeeeee eeeeeeee ‌88‌ ee eeeeeeeeee ee eeeeeeeeeeeee. Me e eeeeee, ee ee eeeeeeeeee eeeeeee eeeeeee ee eeee, eee eeeeeee eeee eeeeeee eeeeeeee eeeeee ee eeeeeee eee eeeeeee eeeeeee ‌88‌, eeee eeeeeeeeeeeeee eeeeeeeee ee eeeeeee eeeeeeeee eeeeeeee, ee eeee e eeeeeeeeee eeeeeeeeee eeeee ee eeeee eee eeeeeeeeeeeee eeeeee. Mee eeeeee eeeeeeeee ‌88‌ eee eeeeeee ee eeeeeeeee ee eeee eeeee. Meeeeeeeeeeee, eeee eeeeeeee eeeeee ee eee eee ee e eeee eeeee eeeeeee(MM) eeee. M eeeeee ee eeeeeeeeeee eeeeeeee ee eeeeeeeee eee M,M-eeeeee eeee eeee eeeeeeee eee eeeee eeeeee eeee ee eeeee ee eeee ee eeeeeeeeeeeee.

‌Meeeee 88‌ Meeeeeeee ee e 8-Meeeeeeeeee eeee e Meeeee M,M-Meeeee[‌888‌]

Meeeeeeeeeee Meeeeeeee

(M)-8-Meeeeeeee-8-[(eeeeeeeeeeeeee)eeeeee]-8,8-eeeeeeeeeeeeeeeeee-8-eee [(M)-‌88‌]:[‌888‌]

MeMe (88.88 eM, 88.8 eeee) eee eeeee eeee eeeeeeee ee e eeeeeeeeee ee (M)-8-eeeeeeeee-8,8-eeeeeeeeeeeeeeeeee-8-eee [(M)-‌88‌; 88.88 e, 88.8 eeee] ee MMM (88 eM) eeeeeeeeee ee 8°M. Meeee eee eeeeeeee, eee eeee eee eeeeeee eee 88 eee, eee eeee MMMM (888 eM) eee MeMMM8Me (8.88 eM, 88.8 eeee) eeee eeeee ee eeeeeeeeee. Meeee eeeee eeeeeee eee 8 e ee ee, eee eeeeeee eee eeeeeeee eeee eee. ee MM8Me eee eeee eeeeeee eeee Me8M. Mee eeeeeee eeeee eee eeeeeeeee, eee eee eeeeeee eeeee eee eeeeeeeee eeee MM8Me8 (8 ×). Mee eeeeeeee eeeeee eeee eeeee (MeMM8) eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeee eeeeeee eee eeeeeeee ee eeeee eeeeeeeeeeeeee (eeeeee eee, eeeeeee/Me8M 8:8) ee eeeeee e eeeee eeeee; eeeee: 88.8 e (88%); ee 888–888°M.

(8M)-8-Meeeeeeee-8-[(8M,8M)-8-(eeeeeeeeeeeeee)-8-(eeeeeeeeeeeeee)-8-eeeeeeeeeee]-8,8-eeeeeeeeeeeeeeeeee-8-eee (‌88‌); Meeeeee Meeeeeeee:[‌888‌]

MMMMMMM: Meeeeeeee eeeee eeeeeeeeeeee eeeeee eeeee ee eeeeeeeeee ee e eeeee eeeeeeeeee, eee ee ee eee eee eeeeeeeeeee eeeee eeeeeeee.

8.88 M MeMe (8.88 eM, 8.8 eeee) eee eeeee ee e eeee ee (M)-8-eeeeeeeee-8-[(eeeeeeeeeeeeee)eeeeee]-8,8-eeeeeeeeeeeeeeeeee-8-eee [(M)-‌88‌; 888 ee, 8.88 eeee] ee MMM (8 eM) eeeeeeeeee ee −88°M. Meeee eeeee eeeeeee eee 88 eee, eee eeeeeee eee eeeeee ee −888°M, eee MeMMM (888 μM, 8.88 eeee) eee eeeee. Mee eeee eee eeeeeee ee eeee ee −88°M eeeeee 88 eee, eee eeee MMMMe (888 μM, 8.88 eeee) eee eeeee. Mee eeeeeee eee eeeeeee eee 8 e ee ee, eee e eeeeeeeee eeeeeeeeeee eeee eeeeee eee eeeeeeeeeee ee eee eeeeeeee ee MM8Me8, eeeeee eee eeeeeeee eee eeeeeeee ee eee eeeeeeeeeeee ee eee. ee MM8Me. Mee eeeeeee eeeee eee eeeeeeeee, eee eee eeeeeee eeeee eee eeeeeeeee eeee MM8Me8 (8 ×). Mee eeeeeeee eeeeeee eeeee eee eeeeeeee eeee eeeee (MeMM8) eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeee eeeeeee eee eeeeeeeeee eeee eee eeeeee (8 ×) eee eeeeeeeeeeeeee (MeMM/MM8Me8) ee eeee eee eeeee eeeeeeee ee e eeeeeeeee eeeee eeeeeeeeee e eeeee eeeeee ee eee M8 eeeeee (ee 88.8:8.8); eeeee: 8.88 e (88%); ee 888–888°M.

(M)-8-(Meeeeeeeeeeeee)-8-eeeeeeeeeeeee (‌88‌); Meeeeee Meeeeeeee eee M,M-Meeeee ee Meeeeeee ee Meeeeee Meeeeeeeee:[‌888‌]

MMMMMMM: Meeeeee eeeee eee eeeeee eeeee eeeeeeee. Meeeee eeeeeeee eee eeeeeeee eee eeeeeeeee.

Me(MMMMM8)8 (8.888 e, 8.88 eeee) eee eeeee ee e eeeeeee eeee ee eee eeeeee eeeeeeeeeeeee ‌88‌ (8.888 e, 8.88 eeee) ee MMM/MeMM/M8M (8:8:8, 8 eM) eeee ee ee. Meeee eee eeeeeeee, eeeeeeee eee eeeeeeeee eee 8 eee, M8M eee eeeee, eee eeee eee eeeeeee eee eeeeeee eeee Me8M. Mee eeeeeee eeeee eee eeeeeeeee eee eee eeeeeee eeeee eee eeeeeeeee eeee Me8M (8 ×). Mee eeeeeeee eeeeeee eeeee eee eeeeeeee eeee eeeee (MeMM8) eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee ee eeee eee eeeee eeeeeeeeee, eeeee eee eeeeeeeeeee ee MMM/M8M (8:8, 8 eM). Meee eeee eee eeeeee ee 8°M eee MeMM8 (88 ee, 8.88 eeee) eee MMM (88 μM, 8.88 eeee) eeee eeeee ee eeeeeeeeee eeee eeeeeeee. Meeee eeeee eeeeeeeee, eee eeeeeee eee eeeeeee eee 88 eee, eeeeee eee. ee MM8Me eee Me8M eeee eeeeeeeeee eeeeeee eeeeeeeeeeeee ee e eeeee. Meee eeeeeeee eee eeeeeee ee eeeeeeeeee. Me eee eeee eeeeee ee eeeeeeeeee eeee eee. ee MM8Me eeee, M8M, eee Me8M, eee eeee eeeee eeeee eeee eeeeee ee eeeeeee eee eeeeee eeeeeeeeeeeee (M)-‌88‌ ee e eeeee eeeee; eeeee: 8.888 e (88%). Mee eeeeeeee eee eeeeeee eeee Me8M, eee eeeeeee eeeee eee eeeeeeeee, eee eee eeeeeee eeeee eee eeeeeeeee eeee Me8M (8 ×). Mee eeeeeeee eeeeeee eeeee eee eeeeeeee eeee eeeee (MeMM8) eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee ee eeee eee eeeee eeeee eeeeeeee, eeeee eee eeeeeeee ee eeeee eeeeeeeeeeeeee (eeeeee eee, eeeeeee/MeMMe 8:8); eeeee: 8.88 e (88%); >88% ee.

References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) M 8, 888.