Science of Synthesis

Pineschi, M.; Boldrini, C., Science of Synthesis: Advances in Organoboron Chemistry towards Organic Synthesis, (2019) 1, 220.

Epoxides (e.g., ‌91‌) react readily with lithiated bis[(pinacolato)boryl]methane at the less-hindered position. Functionalized 1,3-hydroxyboronates ‌92‌ are obtained through a subsequent one-pot copper-catalyzed cross-coupling reaction. The cross-coupling step is catalyzed by copper(I) chloride, without the need for an external ligand, with allylic halides being the best coupling partners. To achieve good conversion, the reaction requires heating to 60 °C in tetrahydrofuran (‌Scheme 26‌).[‌25‌] The reaction proceeds with retention of configuration at the more-substituted (non-reacting) carbon of the epoxide. Due to the instability of the direct coupling products ‌92‌ during chromatography on silica gel, they are isolated after derivatization of the hydroxy moiety as the tert-butyldimethylsilyl ethers ‌93‌. Aryl-substituted epoxides ‌91‌ give good yields and diastereomeric ratios and alkyl-substituted epoxides ‌91‌ give higher yields but with very low diastereomeric ratios. Cyclohexene oxide [‌91‌, R1 = H; R2,R3 = (CH2)4] gives good yield and diastereomeric ratio, but requires a longer time for the ring-opening step. Trisubstituted epoxides ‌91‌ also react with this protocol, but the first step requires harsher conditions (heating to 45 °C for 24 hours).

‌Meeeee 88‌ Meeee-Meeeeeeee Meeeeeeee ee Meeeeeee eeee Mee[(eeeeeeeeee)eeeee]eeeeeee eee Meeee Meeeeee[‌88‌]

‌Meeeeeeeeee 88‌

M8	M8	M8	ee	Meeee (%)	Mee
M	Me	M	8:8	88	[‌88‌]
M	8-Mee	M	88:8	88	[‌88‌]
M	8-MM8M8	M	88:8	88	[‌88‌]
M	8-Mee	M	88:8	88	[‌88‌]
M	8-Mee	M	88:8	88e	[‌88‌]
M	(MM8)8Me	M	8:8	88	[‌88‌]
M	Me	M	8:8	88	[‌88‌]
M	MM8MMMMMM	M	8:8	88	[‌88‌]
M	Me	M	8:8	88	[‌88‌]
M	(MM8)8		88:8	88e	[‌88‌]
Me	Me	M	8:8	88e,e	[‌88‌]
		M	8:8	88e,e	[‌88‌]
Me			88:8	88e	[‌88‌]

e Meee-eeeeeee eeee eeeeeeeee ee 88 °M eee 88 e.

e Meeeeeee ee eee eeee eeeee eeeeeeeee ee eee M—M eeee eeee M8M8/MeMM.

e Meee-eeeeeee eeee eeeeeeeee ee 88 °M eee 88 e.

Mee eee ee eeeee eeeeeee ‌88‌ eeeee eeee eeeee eeeeeee ee eeeee-eeeeeeee eeeeeeee eee eeee eeee eeeeeeee. Meeee eeeeeeee eeee eee eeeeeeeeeeee eeeeeeee eeee eee eeeeeeee ee (M)-8-eeeeeeeeeeeee (‌88‌) eee eeeeeeeee eee[(eeeeeeeeee)eeeee]eeeeeee eeeeeeeee 8,8-eeeeeeeeeeeeeeee ‌88‌, eeeee eee ee eeeeeeeeeee eeee 8,8-eeeee ‌88‌ ee eeeeeeee eeeeeeee/eeeeee eeeeeeeee eeeeeeeee. Meeeeeeeee eee eeeeeeeeeeee eeeeee eee eeeeee eeee ee eeeee eeeeeee ‌88‌ eeeeeeeee eeeee ee eeeee eeeeeeeeeeeeeeeeeeee (‌Meeeee 88‌).[‌88‌]

‌Meeeee 88‌ Meeee Meeeeee Meeee ee eee Meeee-Meeeeeeee Meeeeeee ee Meeeeeee[‌88‌]

‌Meeeeeeeeee 88‌

M8	M8	M8	M8	ee	Meeee (%)	Mee
M	M	M	Me	8:8	88	[‌88‌]
M	M	Me	M	88:8	88	[‌88‌]
M	Me	M		8:8	88	[‌88‌]
M	M	(MM8)8		88:8	88	[‌88‌]
M	Me	M	Me	8:8	88	[‌88‌]
M	M	Me	M	8:8	88	[‌88‌]
(MM8)8		M	M	8:8	88	[‌88‌]
M	M	M	MM=MM8	8:8	88	[‌88‌]

Meeeeeeeeeee Meeeeeeee

8,8-Meeeeeeeeeeeeee ‌88‌; Meeeeee Meeeeeeee:[‌88‌]

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8,8-Meeee ‌88‌; Meeeeee Meeeeeeee:[‌88‌]

Me e eeeeee eeeeee eeee M8, ee 8-eM eeee eee eeeeeeee eeee e eeeeeeee eeeeeee eee. Mee[(eeeeeeeeee)eeeee]eeeeeee (‌88‌; 88 ee, 8.88 eeee) eee eeeee eee eeeeeeeee ee MMM (8.8 eM). Mee eeee eee eeee eeeeee eeee e eeeeee-eeeee eee. MMMM (88 ee, 8.888 eeee) eee eeeee ee e eeeeeeee 8-eM eeee eee eeeeeeeee ee MMM (8.8 eM), eee eee eeee eee eeeeee eeee e eeeeee-eeeee eee. MeMe (8.8 ee, 8.888 eeee, 88 eee%) eee eeeeeee eeee e eeeee 8-eM eeee eeeeeeee eeee e eeeeeeee eeeeeee eee, eee eee eeee eee eeeeee eeee e eeeeee-eeeee eee. Mee eeeee eeee eeeeeee eeee eee eeeeee eee eee eeeee ee eee[(eeeeeeeeee)eeeee]eeeeeee (‌88‌) eee MMMM eeee eeeeee ee 8 °M ee ee eee–eeeee eeee. Mee eeee ee MMMM eee eeeeeeeeeee eee eeeeeee ee eee eeeeeeeeeeeeee eeee, eee eee eeeeeee eee eeeeeee ee 8 °M eee 88 eee. Meee, (M)-8-eeeeeeeeeeeee (‌88‌; 8.8 eeee) eee eeeee ee eeeeeee, eee eee eeee eee eeeeee ee 88 °M, eeeeeee ee eeee eeeeeeeeeee eee 88 eee, eee eeeeeeeeeee eee eeeeeee ee eee eeee eeeeeeeeee MeMe. Me eeeee eeeeeee ‌88‌ (8.8 eeee) eee eeee eeeee ee eeeeeee. Mee eeee eee eeeeee eeee eeee, eee eee eeeeeee eee eeeeeee ee 88 °M eee 88 e eee eeee eeeeee ee ee. Mee. ee MM8Me eee eeeee eee eee eeeeeee eee eeeeeeeee eeee Me8M (8 ×). Mee eeeeeeee eeeeeeee eeee eeeee (MeMM8), eeeeeeee, eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeee eeeeeee eee eeeeeeeee ee MMM (8.88 eM). M eeeeeee eee eee eeeee, eee eee eeeeeee eee eeeeee ee 8 °M ee ee eee–eeeee eeee. 8 M ee MeMM (8.88 eM) eee 88% ee M8M8 (8.88 eM) eeee eeeee. Mee eeee eee eeeeee eeee e eeeeee-eeeee eee eeee eee eeeeeee eeee e eeee eeeeee eee eee eeeeeee eee eeeeeee ee eeee ee ee, eeeeeee ee eeee eeeeeeeeeee eee 8 e, eee eeee eeeeee ee 8 °M ee ee eee–eeeee eeee. Mee. ee Me8M8M8 eee eeeee eee eee eeeeeee eee eeeeeeeee eeee Me8M (8 ×). Mee eeeeeeee eeeeeeee eeee eeeee (MeMM8), eeeeeeee, eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeeeeeee eeeee eeeeeee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee, eeeeeee/MeMMe). Meeeeee eee eeee eeeeeee eee eeeeeeeeee eeeeeeeeeeee ee e eeeeee eeeeeeeeee eeeee e 8:8 eeeeeee ee M8M eee MeMM eeee e 88 °M eeeee eeee.

References