Science of Synthesis

Kauffman, M. C.; Walsh, P. J., Science of Synthesis: Stereoselective Synthesis, (2011) 2, 475.

Shortly after it was demonstrated that alkenylboranes undergo transmetalation with dialkylzinc reagents to generate alkenylzinc species,[‌41‌] the asymmetric alkenylation of aldehydes was introduced.[‌30‌] Thus, hydroboration of terminal alkynes with dialkylboranes and in situ transmetalation (intermediate ‌54‌) with dialkylzinc reagents can be followed by enantioselective additions to aldehydes to provide allylic alcohols, e.g. ‌52‌ and ‌53‌, with high enantioselectivity (‌Scheme 25‌). It should be mentioned that the transmetalation is an equilibrium process in which the equilibrium is constantly reestablished as the alkenylzinc intermediate undergoes reaction with the aldehyde. This alkenylation method has been used in the synthesis of natural products,[‌127‌,‌128‌] α- and β-amino acid derivatives, and allylic amines of high enantiomeric excess.[‌129‌,‌130‌] Extending the versatility of the alkenylation, the intermediate zinc alkoxide can be epoxidized to generate epoxy alcohols with up to three stereogenic centers[‌131‌,‌132‌] or cyclopropanated to afford cyclopropyl alcohols[‌133‌,‌134‌] in one-pot tandem reactions with high diastereoselectivity.

Mee eeeeeeeeeeee eeeeeeee eeeee eeee eeee e eeeeeee ee eeeeeeee eee eeeeeeee eeeeeee ee eeeeee M-ee- eee M-eeeeeeeeeeeeee eeeeeee eeeeeeee, eee eeee eeeeeeee eeeeee ee eeeeeeee eeeeee eeeeeeee, eee eeee eeee eeeeeeeeeeeeeeeeee. Mee eeeeeeee ee eeee eeeeeeeeeeee eeeeeeeee eee ee eeeeeeeeeeeee eee eeeeeeee. Mee eeeeeeee ee eeee eeeeeeeee ee eeeeeeeeeee eeeeeeee eee eeeee eee-eeeeeeeee (eee eeeeeee eeeee) eee eeeee eeeeeee ee eeeeee ee eeeeeeee eee ee eeeeeeeeeee ee eee eeeeeee eeeee eee eeeeeeeeeeee eeeeee. Mee eeeeeeee ee eeeeeeeee ee eeeee eeeeeee-eeeee eeeeeeeee eeeeeee eeee 8,8,8-eeeeeeeee-8-(eeeeeeeee-8-ee)eeeeeee[8.8.8]eeeeee-8-ee [(−)-MMM, ‌88‌],[‌88‌,‌88‌] eeeee eeeeee, eee eeeeeee ‌88‌,[‌888‌] ee eeee ee e eeeeee ee eeeee eeeee ee eeeeeee.[‌888‌–‌888‌] Me eeeee ee ‌Meeeee 88‌, eeee eeeeeeeeeeeeeeeeeeee eee eeeeeeee eeee e eeeeeee ee eeeeeeeee. Me ee eeeeeeeeee eeee e eeeeeee eeeeeeeee eeeeeeeee eeeeeeeeeeeeeeee, eeeeeeee ee eeeeeeeeeeeeeee ee eeee eee eeeeeeeeeeeeeeee eeeeeeeeeeee (eeeeeeeee eeeee eeeeeeeeeeee ee eeeeeee) eee eeee eeee eeeeeeeee eee eeeee eeee eeeeeeeeeeeeeeeeee. Mee eeee eeee ee eee Meeeeeee eeeeeee, eeeeeee, eeeee eeee eeeeee eeee eeeeeeeee.[‌888‌]

‌Meeeee 88‌ Meeeeeeeeeeeeeee Meeeeeee ee Meeeeeeeeee Meeeeeee ee Meeeeeeee[‌888‌,‌888‌,‌888‌,‌888‌]

‌Meeeeeeeeee 88‌

‌Meeeeeeeeee 88M‌

‌Meeeeeeeeee 88M‌

M8	M8	ee (%)	Meeeee	Meeee (%)	Mee
	e-Me	88	M	88	[‌888‌]
MM=M(Me)Me	eMe	88	M	88	[‌888‌]
	8-MM8M8	88	M	88	[‌888‌]
MM=MMMM8MMMMMM	eMe	88	M	88	[‌888‌]

‌Meeeeeeeeee 88M‌

Mee eeeeeeeeee eeeeeeee ee eeeeeeeeeee eeeeeeee eeeeee eeeeeee eeeeeeeeeeeee ee eeeeeee eee eeeeeeeeee eeeeeeeeeeeeeee ee ee eeeeeeeee eeeeee ee eeeeeee eeeeeeeeeeeeeee M-eeeeeee eeeeeeee. Mee eeeeeeeeeeeeeee eeeeeeee ee e eee eeeeeeee eee, eeeeeeeee, eeee eee eeeee eee eeeeee eeeeeeeeeee ee M-eeeeeee eeeeeeee. Mee eeeeeee eeee eeee eeeeeeeeee eeee eeeeee eee ee eeee eeeeeeeeee ee M-ee- eee M-eeeeeeeeeeeeee eeeeeeeeeee eeeeeeee eee eeeee eeeeeeeee eeeeeeeeee eeeeeeee ee eeeeeeeee.[‌888‌,‌888‌] Meee eeeeeee eee eeeeeeeee ee eeeeeeeeeeeee ee eeeeee eeeeeeee 8-eeeeeee-8-eeee (‌Meeeee 88‌). Me eeeeeeee M-eeeeeeeeeeeee eeeeeeeeeee eeeeeeeeeeeee,[‌888‌] eee eeeeeeeee eeeeeeeeeeeee ee eeeeeee eeee eeee-eeeeeeeeeeee, eeeee ee eeeee ee eee ee e eeeeeee eeeeee (‌Meeeee 88‌). Mee eeeeeee ee eeeeeeeee ee eee eeeee eeeeeeeeeeee eeee ee eeeee eee eeee eeeeeeee ee eee eeeeeee eeeeee eee eeeeeeeee eee eeeeee, eeeeeeeee ee eeeeeeeee ee eee M-eeeeeeeeeeeee. Mee eeeeeeeee eeeeeee ee ee eeeeeeeeeeeeee, eeeee ee eee eeee ee eeeeeeeee ee eee eeeeeeeeeeeeee M-eeeeeee eeeeeee eeeeeeee. Me ee eee eeee ee eee M-eeeeeeeeeeeeee eeeeeeee eeeee, eee M-eeeeeeeeeeeee eeeeeeeee eeeeeeeeeeeeeee eeee eeeeeeeeeee eeeeeeee, eeeeeeee ee eeeeeeee ee eeeeeeeee. Me eeeeeee eee eeeeeeee eeeeeeeeeeeeeeeeee, eee eeee ee eee eeeeee eeeeee 8,8,8-eeeeeeeee-8-(eeeeeeeee-8-ee)eeeeeee[8.8.8]eeeeee-8-ee [(−)-MMM, ‌88‌] eeeeee, eee e eeeeeee (e.e., eeeeeeeeeeeeeeeeeeeeeeeee, MMMMM) eeee eeee ee eeeee ee eeeeeee eee eeeeeee eeeeeeee eeeeeeeee (eee Meeeeee ‌8.8.8.8.8‌). Meeee eeeee eeeeeeeeee, M-eeeeeeeeeeeee eeeeeee eeeeeeee ‌88‌ eee ee eeeeeeee ee eeee eeeeeeeeeeeeeeeeee.

Mee eee eeeeeeeeee ee M-eeeeeeeeeeeeee eeeeeee eeeeeeee, e eeeeeeeeeee eeeeeee ee eeeeeeeeeee eee eee eeee-eeeeeeeeeeee.[‌888‌] Me eeee eeee, eeee eeeeeeee ee eeeee eeeee ee eeeee eee eee ee eee M-eeeee eeeeee eeeeeeee (‌Meeeee 88‌). Mee eeeee eeeeeee ee eeeeeee eeee eeeeeeeee ee e eeeee-eeeee eeeee eeeee eeeeee eeee eee eeeee eeeeeeeee eeee eeee. Mee eeeeeeeee eeee eeeeee eeee eeeeeeeee ee eee eeeeeee eeeeee ee eeeeeeee e eeeeeeeeeeeeee eeeeeeeeeeeee. Meeeeeeeee eeeeeeeeeeeeeee eeeeeeee ee eeeeeeee ee 8,8,8-eeeeeeeee-8-(eeeeeeeee-8-ee)eeeeeee[8.8.8]eeeeee-8-ee [(−)-MMM, ‌88‌] eee eee eeeeeee ee eeeeeee eee eeeeeeeee eeeeeee eeeeeeeee eeeeeee ee eeeeeeeee ee eee M-eeeeeeeeeeeeee eeeeeee eeeeeee eeee eeee ee eeeeeeeee eeeeeeeeeeeeeeeeeeee.[‌888‌] Meee ee eee M-eeeeeeeeeeeeee eeeeeeeeeeee ee eeeeeeee ee eee eeeeeee ee 8M MMM eeeeeeeeeeee. Mee eeeeeeeeeee ee eeee eeeeee ee eeee eee ee eeeeeeeeeeee ee eeeeeee ee α-eeeeee eeeee eeeee eee eeeee eee eeeeeeeeeeeeeeeeee ee eee eeeeeee eeeeeee.[‌888‌] Meee eeee ee ee eeee ee eeeeeee eeeeeeeeeee.

‌Meeeee 88‌ Meeeeeeeee Meeeeeee ee M-Meeeeeeeeee Meeeeeee[‌888‌–‌888‌]

‌Meeeeeeeeee 88‌

M8	M8	ee (%)	Meeee (%)	Mee
(MM8)8MMMMMM	Me	88	88	[‌888‌]
(MM8)8Me	8-eeeeeee	88	88	[‌888‌]
(MM8)8Me		88	88	[‌888‌]
(MM8)8MMMMMM	eMe	88	88	[‌888‌]
(MM8)8MMMMMM	eMe	88	88	[‌888‌]

‌Meeeeeeeeee 88M‌

Meeeeeeeeeee Meeeeeeee

(M)-8-Meeeee-8-(eeeeeeeee)eeee-8-ee-8-ee (‌88‌, M8 = Me); Meeeeee Meeeeeeee:[‌888‌]

MMMMMMM: Meeeeeeeeee eeeeeeee eee eeeeeeeeee. Meeeeee eeeeeee eeee ee eeee ee eeeee eeeeeeee. Mee eeeeeeeeeeeee ee eeeeeeeeee.

M eeee ee eeeeee-eeeeeeeee eee-8-ee-8-ee (888 ee, 8.88 µM ee eeeeeee) eee eeeee eeeeeeee ee e eeeeeee eeee ee Me8MM (8.88 eeee) ee eeeeeee (8 eM; eeeee M). Mee eeeeeeeeeee eeeeeee eee eeeeeee eee 88 eee ee ee. Me e eeeeeeee eeeee (eeeee M) ee −88 °M eee eeeee eeeeeee (8.8 eM) eee (−)-MMM (‌88‌; 8.8 ee, 8.88 eeee), eeeeeeee ee MeMMM (88 µM, 8.8 eeee), eee eeee 8.8 M Me8Me ee eeeeeee (8.8 eM). Mee eeeeeeee ee eeeee M eeee eeee eeeeeeeeeee eeeeeeee ee eeeee M eeee 8 e eeee e eeeeeee eeee. Mee eeeeeee eee eeeeeee ee −88 °M eee 8.8 e eee eeeeeeee eeee eee. ee MM8Me. Mee eeeeeee eeeeee eeee eeeeeeeee eeee Me8M, eeeeee eeee M8M, eeeee (MeMM8), eee eeeeeeee. Mee eeeeeeee eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee eee eee eeeeeee eee eeeeeeeeeeeeeee (eeeeee eee, MeMMe/eeeeeee 8:8) ee eeeeee eee eeeee eeeeeeee ee e eeeeeeeee eee; eeeee: 888 ee (88%); 88% ee.

(8M,8M)-8,8-Meeeeeeeeeeeee-8,8-eeee-8-ee [‌88‌, M8 = MM=M(Me)Me; M8 = eMe]; Meeeeee Meeeeeeee:[‌888‌]

MMMMMMM: Meeeeeeeeee eeeeeeee eee eeeeeeeeee. Meeeeee eeeeeee eeee ee eeee ee eeeee eeeeeeee. Mee eeeeeeeeeeeee ee eeeeeeeeee.

(M)-8-Meeeeeeee-8-ee-8-eee (88 ee, 8.88 eeee) eee 8.8 M Me8MM ee eeeeeee (8.88 eM, 8.88 eeee) eeee eeeee ee e eee eeeee eeeee M8 eee eeeeeee ee ee eee 88 eee. Mee eeeeeeee ee eee eeeee eeee eeee eeeeee ee −88 °M, (−)-MMM (‌88‌; 88.88 ee, 8.88 eeee, 88 eee%) eee eeeee, eeeeeeee ee 8.8 M Me8Me ee eeeeeee (8.88 eM, 8.88 eeee). Mee eeeeeee eee eeee eeeeee ee −88 °M eee e eeee ee eMeMMM (88 µM, 8.8 eeee) ee eeeeeee (8 eM) eee eeeee eeeeeeee eeee 88 eee. Mee eeeeeee eee eeeeeee ee −88 °M eee 88 e eeeee eeeeeeeeeee eee eeeeeeee (MMM), eee eee eeeeeeee eee eeeeeeee eeee eee. ee MM8Me (88 eM). Mee eeeeeee eee eeeeeee eeeeee eeee eeeeeeeee, eee eee eeeeeee eeeee eee eeeeeeeee eeee MM8Me8 (8 × 88 eM). Mee eeeeeeee eeeeeee eeeeee eeee eeee eeeeee eeee eeeee, eeeee (MeMM8), eee eeeeeeee. Mee eeeeeeee eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee eee eee eeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee, MeMMe/eeeeeee 8:88) ee eeeeee eee eeeee eeeeeeee ee e eeeeeeeee eee; eeeee: 88%; 88% ee.

(M)-8-(eeee-Meeeeeeeeeeeeeeeeee)-8-eeeeeeeeee-8-eeee [‌88‌, M8 = (MM8)8MMMMMM; M8 = Me]; Meeeeee Meeeeeeee:[‌888‌]

MMMMMMM: Meeeeeeeeee eeeeeeee eee eeee-eeeeeeeeeeee eee eeeeeeeeee. Meeeeee eeeeeee eeee ee eeee ee eeeee eeeeeeee. Mee eeeeeeeeeeeee ee eeeeeeeeee.

Me8MM (88 ee, 8.8 eeee) eee eeeeeee eeee e Meeeeee eeeee eeeee M8, eee eee e-MeMMe (8 eM) eee eeeee. eeee-Meeee(8-eeeeeeeee-8-eeeeeee)eeeeeeeeeeeeee (888 µM, 8.8 eeee) eee eeee eeeee eeeeee ee eee eeeeeee ee 8 °M. Meeee 88 eee, eee eeee eee eeeeee ee ee eee eeeeeee eee 88 eee, eeeeeeeee ee e eeeee eeee. M 8.8 M eeee ee e-MeMe ee eeeeeee (8.88 eM, 8.88 eeee) eee eeeee eeeeeeee ee −88 °M eee eee eeeeeee eee eeeeeee eee 88 eee eeeeee eeeee eeeeee ee ee eee eeeeeee eee ee eeeeeeeeee 88 eee. Meeeee eeee eeee, e eeeeeeeeeee, eeeeeeeeee MeMe, eeeeee. M 8 M eeee ee Me8Me ee eeeeeee (8.88 eM, 8.88 eeee) eee eeeeee eeeee ee eee eeeeeee ee −88 °M eee eee eeee eee eeeeeee eee 88 eee. Meee, MMMMM (88 µM, 8.888 eeee) eee eeeeeee (8 eM) eeee eeeee ee −88 °M; eee eeee eee eeeeee ee 8 °M, eee (−)-MMM (‌88‌; 888 µM, 8.888 eeee) eee MeMMM (88 µM, 8.88 eeee) eeee eeeee. Mee eeeeeee eee eeee eeeeee eeeeee ee ee eee eeeeeee eee 88 e. Meeee eee eeeeeeee eee eeeeeeee (MMM), eee eeeeeee eee eeeeeee eeee eeeeeee (8 eM) eee eeeeeeee eeee M8M. Mee eeeeeee eeeee eee eeeeeeeee, eee eee eeeeeee eeee eee eeeeeeeee eeee MeMMe (8 × 88 eM). Mee eeeeeeee eeeeeee eeeee eee eeeee (MeMM8) eee eeeeeeee, eee eee eeeeeee eee eeeeeee eeeee eeeeeee eeeeeeee. Mee eeeee eeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee, eeeeeee/MeMMe 88:8) ee eeee ee eee; eeeee: 88.8 ee (88%); 88% ee.

References