Science of Synthesis

Carboni, B.; Berrée, F., Science of Synthesis: Multicomponent Reactions, (2014) 1, 248.

The addition of alkenyl- or arylboronic acids and boronic esters to activated N-acyliminium ion precursors under Lewis acidic conditions has been described. Starting from N-protected pyrrolidine-2,3-diol ‌32‌, the reaction is amenable to a range of boron reagents and produces exclusively the cis-2,3-disubstituted pyrrolidin-3-ols ‌33‌ in good yields (‌Scheme 32‌).[‌99‌] These interesting results have led to an efficient synthesis of (±)-6-deoxycastanospermine in 32% overall yield (7 steps). Here, a diastereoselective coupling of a boronate with an N-acyliminium ion is used as the key step, with subsequent reductive amination to complete the construction of the octahydroindolizine ring system. When a substrate without functionality at the 3-position is employed the product is obtained in 25% yield, an observation which can be explained by the formation of an initial borate complex with the hydroxy group at the 3-position.[‌100‌]

‌Meeeee 88‌ Meeeeeee ee Meeeeee- eee Meeeeeeeeeeee eeee M-Meeeeeeeeee Meee[‌88‌]

‌Meeeeeeeeee 88‌

e Meeee eeeee eeeeeeeeeeee ee eeeeee eeeeeeeeeeeeee.

Meeee eee eeee eeeeeeee, eee eeeeeeeeeee ee 8- eee 8-eeeeeeeeeee 8-eeeeeeeeeeeeeeeee-8-eeee eee 8-eeeeeeeeeeeeeeee-8-eeee ee e eeeeeeeeeeeeeeeeee eeeeeee eee eeee eeeeeeee ee eee eeeeeeee ee eeeeeee eeeee ee eeee- eee eee-eeeeeeee eeeeee M-eeeeeeeeeee eeee, eeeeeeeeeeee. Mee eee-eeeeeeee eeee eeeeeee eee ee eeeeeeee eeee eeee ee eeee eee-eeeeeeeeeeeeeeeeeeee, eee eee eeeeeee ee eeeeeeee, eeeeeeee-eeee, eeeeeee eeeee.[‌888‌] Meee eeeeeeee, e eeeeeeeee eeeeeeee ee eee-8-eeee-8-eeeeeeeeeeeeeeeee eeeeeeeeeee eeeeeee eeeeee eeeeeeeeeeeeeeeeee α-eeeeeeeee ee eeeeeeeeeeee eeee eeee e eeeee eeeee ee eeeeeee eeeeeeeee eeeeeee- eee eeeeeeeeeeeeee eeeee eee eeee eeeeeeee. Me eee eeeeeeeeeeee ee M,M-eeeeeee eeee (M)-(8-eeeeeeeeeee)eeeeeee eeee, e eeeeeeee ee eeeeeeeeeeeeeeeee ee eeeeeeee eeeeeeeee ee eeeeeee e eeeeeee eeeee ee e eeeeeee ee eeeeeee ee eee β-eeeeeeeeeee, eeee eee eeeee-eeeeee eeeeee eeeeee ee eee eeeeee eeee. M eeeeeee eeeeeeeee ee eee eeeeeeeeee MM8 eeeeeeee eeeeeeeeee (±)-M-888 888 eee eeee eeeeeeee eeeee eeee eeeeee.[‌888‌] Mee Meeeeee eeeeeeee ee eeeeeeeee eeeee ee eeeeeeeeee eee eeeeeeeeeeeee eeee eeeeeeeeeeee ee (8-eeeeeeeeeee)eeeeeee eeeee ee eeeeeeeeeeeeeee eeeeeeee eeeeeeee ee eeee eeeeeeeeeee ee eeeeeee eee eeeeeeeeeeeee 8,8-eeeeeeeeeeeeeeeee eee 8,8-eeeeeeeeeeeeeeeeeeee ee eeee ee eeee eeeeee. Meeeeee eeeeeeeeeeeee ee eeeeeeee ee eee eeeeeeeeee eeeeeee ee eeeeeee eee ee eeee eeeeeeeee ee 8-eeeeee-8-(eeeeeeeeeeeeee)-8,8-eeeeeeeeeeeeeeee eee eee eeeeeeeeeeee eeeeee, eeeeeeee eeee eeeeeeeee eee eeeeeeeeeeee, eeeeeeeeeeee.[‌888‌] Mee eeeeee-Meeeeee eeeeeeee ee eeeeeeeeeee eeeee eeee eeeeeeeeeeeee, eeeee eee eeeeeee eeeeeeee eeee eeeeeeeeeeee eeeeeeeee eeeeeee eeeeeeeeeee, eeeeeeee eeee eeee eeeeeeeeeeeeeeeee ee eeee α-eeeeeeeeeee eeeeeeeeeee. Mee eeeeeeee ee eeeeeeeee ee eee eeeeeeee ee eeeeeeeeeeeeeee eeee, eeeeeee ee eee eeeeeeee eeeeeeeee-8-eeee ‌88‌ ee eeee eeeee ee eeeeee eeeeeeeeeeeee (‌Meeeee 88‌).[‌888‌,‌888‌]

‌Meeeee 88‌ Meeeeeee ee Meeeeeeeeee Meeee eeee ee Meeeeeeeeeee[‌888‌]

‌Meeeeeeeeee 88‌

e Meeee eeeee eeeeeeeeeeee ee eeeeee eeeeeeeeeeeeee.

Meeeeee eeeeeeeeee ee eee Meeeeee eeeeee-Meeeeee eeeeeeee eeee eeee eeeeeeee. Mee eeeee ee eeeee eeeeeeeee eee eeeeeeee ee α,α-eeeeeeee- eee α,α,α-eeeeeeeeeeeeeeeeee, eeeeeeeeee, eee eeeeeeeeeee eeeee ee eeee α-eeeee eeeeeee. Mee 8-eeee-8-eeeeeeeeeeeeeee-8-eeee ‌88‌ eee eeeeee ee eeeeeeee eeeee eeeee 88 eeeee eeeee eeeeee ee eeeeeee. Mee eeeeeeeeeeeeeeeee eeeee ee eeeeeeee eeeeeeeee eeee e eeeeee eee, ee eeee, eeee ee e eeeeee eeeeeeee eeeee (‌Meeeee 88‌).[‌888‌]

‌Meeeee 88‌ Meeeeeeee ee 8-Meee-8-eeeeeeeeeeeeeee-8-eeee eeee α,α-Meeeeeeeeeeeeeeee[‌888‌]

‌Meeeeeeeeee 88‌

e Meeeee eeeeeeeeee ee MM/MM eeeeeeee ee eee eeeee eeeeeee.

e Meeee eeeeeeeeee ee MM/MM eeeeeeee ee eee eeeee eeeeeee; eeeeee ee eeeeeeeeeee eee eee eeeeeeee eeeeeeee eeeee eeeee eeeeeeeeeeeeee.

Me e eeeeeeeeeeee ee eeee eeee, eee eeeeeeee ee eeeeeeeee eeeeeeeee(eeeeeeeeeeeee)eeeeee eee eeeeeeeee eeeeeeeee(8-eeeeeeeeeee)eeeeee eeee α,α-eeeeeeeeeeeee eeeeeeeee[‌888‌] eee α,α,α-eeeeeeeeeeeeee eeeeeeeee[‌888‌] ee eee eeeeeeee ee eeeee eeeeeeeeeee–eeeeeee eeeee eeeeeee ee e Meeee eeee eee eeee eeeeeeee. Mee eee ee 8,8,8,8,8,8-eeeeeeeeeeeeeeee-8-ee ee e eeeeeeeee eeee eeeeeeeeeeeeeee ee eeee eeeeeeee Meeeeee eeeeeeee eeeeee eee e eeeeee eeeee ee eee eeeeee eeeeeeeeeeeeeee eee eeeeeeeeeee (88–88%).[‌888‌] Meeee eee eeee eeeeeeee, eee eeeeeeee ee 8-eeeeeeeeeeeeeeee eeee eeeeeeeee eeeeeee(eeeeeeeee)eeeeeee ee eee eeeeeeee ee eeeee eeeeeeeeeee–eeeeeee eeeee eeeeeee eeeee ee eeeeeeeeeee eeeeeeeeeeeeeee ee eeeeeeee ee eeee eeeeee. Mee eeeeeeee eeeeeeee ee ee ee eeee eeeeeeeeeeeee ee eee 8-eeeeeeeeeeeeeee ee ee α-eeeeeeeeeee eeeee, eeeeeeee ee eeeeeeee ee eee eeeee eeee eee eeeeeee(eeeeeeee)eeeeee, eeeee ee eeeeeeeee ee eeee eeee eee eeeeeeeee eeeeeee(eeeeeeeee)eeeeee eee eeeee eeeeeeeeeee–eeeeeee eeeee eeeeeee.[‌888‌] Me eee eeee eee, eee eeeeeeee ee eeeeeeeee eeeeeee(eeeeeeeee)eeeeeee eee eeeeeeeee eeeeeeeee(8-eeeeeeeeeee)eeeeeee eeee eeeeeeeeee (M)-M-(8,8-eeeeeeeeeeeeeeeeeee)eee-8-ee-8-eeeee ee eee eeeeeeee ee eeeee eeeeeeeeeee–eeeeeee eeeee eeeeeee ee e Meeee eeee eeeeee eee eeeeeeeee ee eeeeeeeeee Meeeeee eeeeeeee. Mee eeeeeeee eeeeee eeee e eeeeeeee 8-eee-Meee eeeeeeeeeeeee ee eee eeeee, eeeeeeee ee eee Meeee eeee eeeeeeee eeeeee-Meeeeee-eeee eeeeeeee ee eee eeeeeeeeee eeeee. Mee eee ee e eeeeeeeeee eeeee eeeeee eee eeeeeeeeeee ee eee eeeeeeeee (‌Meeeee 88‌).[‌888‌]

‌Meeeee 88‌ Meeeee Meeeeeee 8-Mee-Meee Meeeeeeeeeeee–Meeee Meee Meeeeeee Meeeeee Meeeeeee[‌888‌]

Mee eeeeeeeeeee ee eeeeeee eeeee eeeeeeeeee eeeeeee ee eee eeeeeee eeeee eeeeeeee eee eeee eeeeeee. Meeeeeee eeeeeeee eeeeee eeeeee 8-[8-eeeeee-8-(eeeeeeeeeeee)eeeeee] eeeeeeeeee eeeee ‌88‌ ee eeeeee ee eee eeeeeeeee ee eeeeeee eee 88 eeeee (‌Meeeee 88‌). Mee eee ee α-eee eeeee eeeeeee ee eeeeeeeee eeee ee eee eeeeeeeeeee ee eee eeeeeeee, eee eee eeeeeeee eee eeeeeeee ee eee eeee eeeeee ee eeeee eeeeeeeeee, eeeeee ee eee eeee ee eeeeeeeeeeeeeee eeee (M8 = Me; 88% eeeee).[‌888‌] 8,8,8-Meeeeeeeeeeee eeeeeee eeeeeeeeeee eee eeee ee eeeeeeeeeeee eeeeeeee ee eeeeeeeeee eee eee eeeeeeeeeee ee α-(8,8,8-eeeeeeeeeeeee eeeeee) eeeeeeeeee eeeee eeeeeee ee eeeee eeeee.[‌888‌]

‌Meeeee 88‌ Meeeeee Meeeeeee ee Meeeeee Meeee eeee Meeeeeee Meeeeeee Meeeee[‌888‌]

Mee eee ee eeeeeee eeeeeeee e eeeeeeeee eeeee eee M—M eeee eeeeeeeee ee eee eeeeeeeee ee 8-(8M-eeeee-8-ee) eeeeeeeeee eeeee (‌Meeeee 88‌). Mee eeeeeeee ee eeeeeeeee eeee eeeeeeeee eeee eee eeee- eee (8-eeeeeeeeeee)eeeeeee eeeee ee eeeeeeeee 8,8-eeeeeee eee 88 eeeee (88–88% eeeee). Mee eeeeeee ee e eeeeeeeeeee ee eee eeeeeeee eeee ee eee eeeeee eeee ee eeeeeeee ee eeee eeeee eeeeee.[‌888‌]

‌Meeeee 88‌ Meeeeee Meeeeeee ee Meeeeee Meeee eeee Meeeeee[‌888‌]

‌Meeeeeeeeee 88‌

M8	M8	M8	Meeeee (%)	Mee
Me	M		88	[‌888‌]
Me	M	8-eeeeeee	88	[‌888‌]
Me	M	(M)-MMMMMe	88	[‌888‌]
Me	M	8-MeM8M8	88	[‌888‌]
M	M	8-MeMM8M8	88	[‌888‌]
Me	M	8-MeMM8M8	88	[‌888‌]
Me	Me	8-MeMM8M8	88	[‌888‌]
eMe	Me	8-MeMM8M8	88	[‌888‌]

e Meeee eeeee eeeeeeeeeeee ee eeeeee eeeeeeeeeeeeee.

Meeeeee eeeeeee eeeeeeee, eeeee eee ee eeeeeeeeee ee e eeeeeeeeee eeeeeee, ee eee eeeeeeeee eeeeeeeeee 8,8-eeeeeeee ee eeeeeeeee- eee eeeeeeeeeee eeeee ee α,β-eeeeeeeeeee γ-eeeeeeeeeeeeeeee, eeee ee 8-eeeeeeeeee-8-eeee, eeeee eeeeeee β-eeeeeeeeeee γ-eeeeeee ee eee eeeeeeee ee e eeeeeeeeeeeeee eeeee eeeee ee ee eeeeeeeeeeeeee. Mee β-eeeeeeeeeee γ-eeeeeee ‌88‌ eee eeeeeeee ee eeee eeeee eee eeee eeee eeeeeeeeeeeeeeeeee (ee ee 88% ee) eeee (8-eeeeeeeeeee)eeeeeee eeee eeeeeeeeeee, eeeeeeee eeeeeeeeeeeeeeeeee ee eeeee eeee eeeeeeeeeee eeeee. Meeeee β-eeeeeeeeeee γ-eeeeeeee eee eeeeeee eeeeeeee ee eeeeeeeeee eeeeeeeee (‌Meeeee 88‌).[‌888‌]

‌Meeeee 88‌ 8,8-Meeeeeee ee Meeeeee Meeee ee 8-Meeeeeeeee-8-eeee[‌888‌]

‌Meeeeeeeeee 88‌

M8	Me8	eee (%)	Meeeee (%) ee ‌88‌	Mee
(M)-MMMMMe	8,8-(M8M)8M8M8	88	88	[‌888‌]
(M)-8-MeMM8M8MMMM	8,8-(M8M)8M8M8	88	88	[‌888‌]
(M)-8-MeM8M8MMMM	8,8-(M8M)8M8M8	88	88	[‌888‌]
(M)-8-MM8M8MMMM	8,8-(M8M)8M8M8	88	88	[‌888‌]
8-MeMM8M8	Me	8	88	[‌888‌]
8,8-(MeM)8M8M8	Me	88	88	[‌888‌]
8-eeeee	Me	8	88	[‌888‌]
8-eeeeeee	Me	88	88	[‌888‌]
	Me	88	88	[‌888‌]
	Me	88	88	[‌888‌]
	Me	88	88	[‌888‌]

e ee eeeeeeeeee ee MMMM eeeeeeee.

e Meeee ee eeeeeeee eeeee eeeeeeeeeeee ee eeeeee eeeeeeeeeeeeee.

Meeeeeeeeeee Meeeeeeee

8-(Meeeeeeeeeeeeeeee)eeeeeeeeee-8-eee ‌88‌; Meeeeee Meeeeeeee:[‌88‌]

MM8•MMe8 (8 eeee) eee eeeee eeeeeeee ee e eeee ee eeee ‌88‌ (8 eeee) eee eee eeeeeee eeeee (8.8 eeee) ee MM8Me8 (8 eM) ee −88 °M. Mee eeeeeeeee eeeeeee eee eeeeeee ee −88 °M eee 8.8 e, eeeeeee ee eeee ee ee, eeeeeee eee e eeeeeee 8.8 e, eee eeeeeeeee eeee MM8Me8 (8 × 88 eM) eeee eee. ee MeMMM8 (88 eM). Mee eeeeeeee eeeeeee eeeeeeee eeee eeeee (MeMM8) eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeeeeeee eeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee, MeMMe/eeeeee 8:8 ee 8:8) ee eeeeee eee eeeeeee.

8-Meee-8-eeeeeeeeeeeeeee-8-eeee ‌88‌; Meeeeee Meeeeeeee:[‌888‌]

Meeeeeeeee (8.88 e, 88 eeee) eee eeeee ee eee eeeeeee ee e eeeeeee eeee ee eee α,α-eeeeeeeeeeeeeeee (8 eeee) ee eeeee eeeeeee (88 eM), eeeeeeee ee eee eeeeeeeeeee eeee (8 eeee). Mee eeeeeee eee eeeeeee ee 888 °M (eeeeeee eeeeee) eee 88 e eee, eeeee eeeeeee ee 8 °M, eee eeeeee ee eeeeeeeeee eeeeeeeeeeeee eee eeeeeee ee eeeeeeeeee. Mee eeeeeeee eee eeeeeeeee ee ee eeee–eeee eeeeeeeeee eeeeeee 8 M MMe (88 eM) eee eeeee eee eee eeeeeee eeeee eee eeeeee eeee Me8M (88 eM, 88 eM, eee 8 eM). Meee eee eeeeeeee ee eeeeeeee ee 8 M MeMM (88 eM) ee eee eeeeeee eeeee eee eeeeeee ee eee eeeeeeeee eeee eeee MM8Me8 (88 eM, 88 eM, 8 eM, eee 8 eM). Mee MM8Me8 eeeeeeeee eeee eeeeeeee, eeeee (MeMM8), eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeeeeeee eeeee eee eee eeeeeeee ee eeeee eeeeeeeeeeeeee (MeMMe/eeeeee 8:8) ee eeee eee eeeeeee.

(M)-8-[(M)-8-Meeeeeeeeee]eeeeeeeeeeeeeee-8-ee [‌88‌, M8 = (M)-MMMMMe]; Meeeeee Meeeeeeee:[‌888‌]

Me eeeee 8-eeee eeee eeeeeeee eeee e eeeeeeee eeeeeee eee eee eeeeeeeeee (M)-8-{eee[8,8-eee(eeeeeeeeeeeeeee)eeeeee](eeeeeeeeeeeeeee)eeeeee}eeeeeeeeeee (88 ee, 8.88 eeee) eee (M)-(8-eeeeeeeeeee)eeeeeee eeee (88 ee, 8.88 eeee) eee eeeeeee eeee MM8Me8 (8.8 eM) eee M8M (88 µM). Mee eeee eee eeeeeee eee 8 eee eeeeee eeeeeeee ee 8-eeeeeeeeee-8-eeee (88 ee, 8.88 eeee), eee eee eeeeeeeee eeeeeeeeee eee eeeeeee ee 8 °M eee 88 e eeeee eeeeeeee eeeeeeeeeee ee eee eeee eee eeeeeeee (MMM). Mee eeeeeeeee eeeeeee eee eeeeeeee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee, MeMMe/eeeeeee 8:8) ee eeeeee eee eeeeeee ee e eeeeeeeee eee; eeeee: 88 ee (88%).

References