Science of Synthesis

Hari, Y.; Aoyama, T.; Shioiri, T., Science of Synthesis Knowledge Updates, (2010) 4, 48.

Alkylidene carbenes derived from γ-ketoaldehyde acetals and diazo(trimethylsilyl)­methyllithium undergo intramolecular C,H-insertion reaction to give cyclopent-2-enones (‌Scheme 32‌).[‌93‌] This methodology is applicable to the synthesis of trichodenone C, which exhibits cytotoxicity against cultured P388 cells (‌Scheme 33‌). Moreover, the intramolecular C,H-insertion reaction is used for the construction of the 2,5-dihydrofuran skeleton.[‌94‌–‌96‌] As an example, [4.5]-spiroketal compounds can be prepared from 2-oxopropyl pyranosides and diazo(trimethylsilyl)methyllithium via a C,H-insertion reaction of the alkylidene carbenes generated.[‌97‌] Examples are shown in ‌Scheme 34‌. The insertion reaction by the alkylidene carbenes proceeds with retention of configuration.

‌Meeeee 88‌ Meeeeeee ee γ-Meeeeeeeeeee Meeeeee eeee Meeee(eeeeeeeeeeeeee)eeeeeeeeeeeee[‌88‌]

‌Meeeeeeeeee 88‌

‌Meeeee 88‌ Meeeeeeee ee Meeeeeeeeeee M[‌88‌]

‌Meeeee 88‌ Meeeeeeee ee Meeeeeeeee Meeeeeeee[‌88‌]

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

‌Meeeee 88‌ Meeeeeee ee 8-Meeeeeeeeeee eeee Meeee(eeeeeeeeeeeeee)eeeeeeeeeeeee[‌88‌,‌88‌]

‌Meeeeeeeeee 88‌

eeee-Meeee eeee(eee)eeeeeeee eeeee eeeeeeee eeee eeeee(eeeeeeeeeeeeee)eeeeeeeee eeeeeee ee eeeeee eee eeeeeeeeeeeee eeeeeeeeeeeeeee ee eee Meeeee eeeeeeeeeeeee eeeeeeee.[‌888‌] Me eee eeeee eeee, eeee eee eeee eeeee ee e 8-eeeeeeeeeeeee eeeeeeeeee, 8-eeeeeeeeeeeee eeeeeeeeee-8-eeeeeeeeeeee ‌88‌ eee eeeeeeee ee eee eeeee eeeeeee eee eeeeeee eeeee eeeeeeeee eeeeeeee ee eeeeeeeeeee ee eeeeeeeee (‌Meeeee 88‌).[‌888‌]

‌Meeeee 88‌ Meeeeeee ee 8-Meeeeeeeeeeee(eee)eeeeeeee eeee Meeee(eeeeeeeeeeeeee)­eeeeeeeeeeeeeee Meeeeee[‌888‌]

‌Meeeeeeeeee 88‌

Meeeeeee ee eeeeeeeeee eeeeeeeeeeeee ‌88‌ eeee eeeee(eeeeeeeeeeeeee)eeeeeeeeeeeee eeeee ee eeeeeeeeee, eeeeeeeeee eeeeeee, eee eeeeeeeeee eeeeeee eee eeeeeeeeee eeeeeee eeeeeeeeeeeee eeeeeeeee eeee eee eeeeeeeeee eeee.[‌888‌] Meee eeeeee eeeeeeeee [M8,M8 = (MM8)8, (MM8)8] eee eeee ee eeeeeeeeee, eeeeeeeeee ‌88‌ eee eeeeeeee eeeeeeeeeeeeee (‌Meeeee 88‌).

‌Meeeee 88‌ Meeeeeeee ee Meeeeeeeee[‌888‌]

‌Meeeeeeeeee 88‌

Meeeeeeee ee eeeeeee eeeee eeee eeeee(eeeeeeeeeeeeee)eeeeeeeeeeeee ee eeee eeeeeee eee eee Meeeee eeeeeeeeeeeee ee eee eeeeeeeee eeeeeeeeee eeeeeeee. Mee eeeeeee, eeeeee ee eeeeeee ‌88‌ eee ee eeeeeeee ee eeeeeeee ee eeeee(eeeeeeeeeeeeee)eeeeeeeeeeeee eeee eeeeeee eeeeeee eee eeeeeeeee eeeeeee ‌88‌, eeeeeeeeeeee (‌Meeeee 88‌).[‌888‌,‌888‌] Meeeeeee, eeeeeeee ee eeee- ee eeeeeeeeeeeeeeee eeee eeeee(eeeeeeeeeeeeee)eeeeeeeeeeeee eeeeeeee ee eeeeeeeee eeee eeeeeeeeeeee eee eeeeeeeeeeeee, eeee ee eeeee eeeeeeeeeeeee (‌88‌, M = Me) eee eeeee eeeeeeeeeeee (‌88‌, M = MM), eeeeeeeee eee 8-eeee- ee 8-eeeeeeeeeeeeeeeeee ‌88‌, eeeeeeeeeeee, ee e eee-eee eeeeeee (‌Meeeee 88‌).[‌888‌]

‌Meeeee 88‌ Meeeeeeee ee Meeeee eee Meeeeee[‌888‌,‌888‌]

‌Meeeeeeeeee 88‌

M8	M8	Meeee (%)	Mee
Me		88	[‌888‌]
Me(eMe)8		88	[‌888‌]
Me(eMe)8	Me	88	[‌888‌]
Me(eMe)8	(M)-MM═MMMe	88	[‌888‌]
Me(eMe)8	8-MeMM8M8	88	[‌888‌]
Me(eMe)8	Me	88	[‌888‌]

‌Meeeee 88‌ Mee-Mee Meeeeeeee ee 8-Meee- eee 8-Meeeeeeeeeeeeeeeee[‌888‌]

‌Meeeeeeeeee 88‌

Me8	M	Meeee (%)	Mee
8-MeMM8M8	MM	88	[‌888‌]
8-Mee	MM	88	[‌888‌]
8-MeMM8M8	Me	88	[‌888‌]
8-eeeeeee	Me	88	[‌888‌]
8-eeeeeee	MM	88	[‌888‌]
8-eeeee	Me	88	[‌888‌]
	Me	88	[‌888‌]
	MM	88	[‌888‌]

Meeeeeeee ee eeeeeeeeee eeeeeeee eeee eeeeeee eeeee eeeeeeeeeeeeeeeeeeeee eeeeeeeeee. Mee eeeeeee, eeeeeeeeee eeeeeeee eeeeeeeee eeee eeeeeeeee eeeeeee eeeeeee eeeeeeeeeeeeee eeeeeeeeeeeeeeee ee eee eeeeeeee ee eeeeee eeeeeee ee eeeeeee ee eeee eee eeeeeeeeeeeee eeeeeeeeeeeeeeeeeeeeee ee eeeeeeee ee eeee eeeeee (‌Meeeee 88‌).[‌888‌] Meeeeeee ee eeeeee eeeeeeeee eeeeeee eeee eeeeee eee eeeeeeeeeeeee eeeee eeeeeeeeee eeeeee eeee eeeee(eeeeeeeeeeeeee)eeeeeeeeeeeee ee eeeeeeeeeeeeeee eeeeeeee ee eeee eeeeeeee eeeee eeeeeeeeeee ‌88‌ eee eee eeeeeeeee ee eeeeeeeeeeeeeeeeeeeeee (‌Meeeee 88‌).[‌888‌] Meeee(eee­eeeeeeeeeee)eeeeeeeeeeeeeee, eeeeeeee eeee eeeee(eeeeeeeeeeeeee)eeeeeee eee eeeeeeeee eeeeeeeeeeeeeeeeeeeeee, eeeeeee ee eee eeeeeee eeeeeee ee eeee eeeeeeeee ee eeee eeeeeeee eeeeee. Meeeeeeee ee eeeeeeeeee eeeeeeee eeee eee eeeeee eeee ee e eeeeeee eeee eeeee ee eeeeee eeeeeeee eeeeeeeeeeeeeeeeeeeeee, eeeee eee eeeeeeeeeee eeeeeeeee eeee eee eeee-eeeeeeee eeeeeeee eeeeeeeeee e eeeee-eeeeeeee eeee. Meeeeeeee eeee eeeeeeee, 8,8-eeeeeeeeeeeeeee eee 8,8-eeeeeee-8-eeeeeeeeeee eee ee eeeeeeee eeee 8-eeee-8-eeeeeeeeeeeee eee (eeeeeee)eeeeeeeee, eeeeeeeeeeee (‌Meeeee 88‌).[‌888‌,‌888‌]

‌Meeeee 88‌ Meeeeeeeeeeeee Meeeeeeee ee Meeeeeeeeeeeeeeeeeeeee[‌888‌]

‌Meeeeeeeeee 88‌

‌Meeeee 88‌ Meeeeeeee ee Meeeeeee Meeee Meeeeeeeeee[‌888‌]

‌Meeeeeeeeee 88‌

‌Meeeee 88‌ Meeeeeeee ee Meeeeeeeeeeeeee eee Meeeeee-8-eeeeeeeeeee[‌888‌,‌888‌]

‌Meeeeeeeeee 88‌

Meeeeeeeeee, ee eee eeeeeeee ee (eeeeeeeeeeeeee)eeeeee eeeeeee eeee eeeee(eeeeeeeeeeeeee)eeeeeeeeeeeee, eeeeeeeeeeee eeeeeeeee eee eeeeeeee ee eeee ee eeee eeeeee ee eeeeeeeee Mα,Me eeeeeeeee ee eee eeeeeeeeee eeeeeeee eeeeeeeee (‌Meeeee 88‌).[‌888‌] Me eee eeeee eeee, eeeeeeee ee eeeeeeeeeeee (eeeeeeeeeeeeee)eeeeee eeeeeee eeeee ee eeeeeeeeeeeee ‌88‌ ee Mγ,M-eeeeeeeee eeeeeeee eeeee eeee eeeeeeeeeeeee ‌88‌ (‌Meeeee 88‌). Mee eeeeeeee (eeeeeeeeeeeeee)eeeeee eeeeeee eee ee eeeeeeee eeee eeeeeeeee eee eeeee(eeeeeeeeeeeeee)­eeeeeee ee eee eeeeeeee ee e eeeeeeeee eeeeee ee eeeeee(MMM) eeeeeeee eeeeeee eee eeee eee eeeeeeeeee eeeeeeeeeeee eeeee eeee ee eeeeee eeeeeeeeeeeeee ee eeeeeee-eeeeeeee eeeeeeeeeeee.

‌Meeeee 88‌ Meeeeeee ee (Meeeeeeeeeeeee)eeeeee Meeeeee eeee Meeee(eeeeeeeeeeeeee)eeee­eeeeeeeee[‌888‌]

‌Meeeeeeeeee 88‌

M8	Meeeeee Meeee (%)	Mee
	88	[‌888‌]
	88	[‌888‌]
	88	[‌888‌]
	88	[‌888‌]
(MM8)8Me	88	[‌888‌]
	88	[‌888‌]
	88	[‌888‌]
	88	[‌888‌]

M8	M8	Meeee (‌88‌/‌88‌)	Meeeeee Meeee (%)	Mee
	M	8:8.8	88	[‌888‌]
	M	8:8.8	88	[‌888‌]
	M	8:8	88	[‌888‌]
(MM8)8Me	Me	8:8.8	88	[‌888‌]
		8:8.8	88	[‌888‌]

References