Science of Synthesis

Hirsch, A.; Vostrowsky, O., Science of Synthesis, (2008) 43, 100.

The syntheses of polyynes and polyyne units with more than two triple bonds[‌271‌] often employ the Fritsch–Buttenberg–Wiechell rearrangement (see Sections ‌43.8.1.2.2‌ and ‌43.8.2.1.5‌) of substituted 1,1-dialkynyl-2,2-dibromoethenes, containing aryl, hetaryl, alkyl, or silyl groups, and initiate the 1,2-migration of an alkyne unit within a carbene or a carbenoid intermediate[‌268‌–‌270‌] by lithium–halogen exchange. The starting materials are obtained via the corresponding ketones by three different routes, namely Grignard-type reactions, Friedel–Crafts acylations, or Corey–Fuchs-type Wittig alkenations.[‌272‌] Some illustrations of the rearrangement process are depicted in ‌Table 12‌. For example, treatment of suitably substituted 1,1-dialkynyl-2,2-dibromoethenes with butyllithium in hexane at −78°C affords hexatriynes in good to excellent yields (‌Table 12‌, entries 1–4).[‌119‌,‌331‌] 1-(Trimethylsilyl)hepta-1,3,5-triyne (entry 5) is obtained similarly in 76% yield and can be subsequently employed in a stereoselective synthesis of (−)-ichthyothereol and its acetate, natural products that are poisonous to fish.[‌332‌] The synthesis of a series of alkatriynols, some of them naturally occurring polyacetylenes, and their silyl-protected derivatives (entries 6 and 7) are also synthesized using the same methodology.[‌333‌] In such cases the parent conjugated terminal triynols are highly labile and rapidly decompose under ambient conditions; however, their stability is increased by substitution. The tert-butyldiphenylsilyl ether (entry 8) can be obtained in five steps starting from but-2-yne-1,4-diol;[‌334‌] the parent triynol is isolated from several species of beggar ticks. 1,6-Diferrocenylhexatriene (entry 10) is obtained from 3-(dibromomethylene)-1,5-diferrocenylpenta-1,4-diyne, also via a Fritsch–Buttenberg–Wiechell alkynyl migration, and the electronic coupling between the two ferrocenyl units in this product can be assessed by voltammetry.[‌335‌] 1,1-Dibromo-2-(phenylethynyl)-2-(propynyl)ethene affords unsymmetrical 1-phenylhepta-1,3,5-triyne (entry 11), which occurs in a range of plant species, in 18% overall yield starting from commercially available phenylpropynoic acid.[‌274‌] One-pot syntheses of a series of 6-substituted 1-phenylhexatriynes are possible starting from 1,1-dibromo-2-ethynyl-2-(2-phenylethynyl)ethene, which when reacted with 2.2 equivalents of butyllithium in toluene/hexanes at −20 to 0°C gives 6-phenylhexatriynyllithium as an intermediate. This salt can be quenched by electrophiles, such as formaldehyde, benzaldehyde (entry 12), carbon dioxide (entry 13), and iodomethane, to provide the corresponding 1-phenylhexatriynes.[‌275‌]

‌Meeee 88‌ Meee-8,8,8-eeeeeee eeee Meeeeee–Meeeeeeeee–Meeeeeee Meeeeeeeeeeeee[‌888‌,‌888‌,‌888‌,‌888‌–‌888‌]

Meeeeeeeee eeeeeee[8.8.8]eeeeeeeeeee ‌888‌ eeeeeee eeeeeeeeee ee eeeeee ee 8°M ee eeee eee eeeeeeee ‌888‌ eeeeeee eee [8+8] eeeeeeeeeee eeeeeeeee ee eeeeee. Meee eeeeee, eeeeeeeee ee eee ee eee eeeeeee eeeeee ee eee eeeeeee eeee eeeee eee eeeeeeeeeee 8,8-eeeeeeeeeeeee eeeeeee ‌888‌ (‌Meeeee 88‌).[‌888‌,‌888‌]

‌Meeeee 88‌ Meeeeee eee e Meeeeeee eeee Meeeeeeeee Meeeeee[8.8.8]eeeeeeeeeee[‌888‌,‌888‌]

M eeeeeeeeeeeee eeeee ee eeeeeeeeeeeee eeeeeee eeeeeeee eeeee ee eeeeeeee eeeeeeeee ee Meeeeee–Meeeee eeeeeeeeee ee eee(eeeeeeeeeeeeee)eeee-8,8-eeeee ee eeeee eeeeeeee. Mee eeeeee eee ee eeeeeeeeeee eeee eee eeeeeeeeeeeee eeeeeeeeeeeeee ‌888‌ eeeeeeeee ee eeeee eeeeeeeeee eee eeeeeeeee eeee eee eeeeeeeeeeeeeee eeeeeeeeeee 8-(eeeeeeeeeeeeee)eeeeeeeeeee ‌888‌ eeeee eeeeeeee Meeeeee–Meeeeeeeee–Meeeeeee eeeeeeeeee (‌Meeeee 88‌).[‌888‌] Meee eeeeeeee ee eeee ee e eeeeeeeee ee e eeeeeeeeee eeeeeeeee eeeeeee eeeeeee eeee e Meeeeeeeeeeee eeeeeee[‌888‌] eeeeeeeee eee eeeeeeeee eeeeeeeee ‌888‌ ee eeeee eee M8 eeeeeeeeeee ee ee (M)-8-(8-eeeee)eeeee eeeee (‌Meeeee 88‌).[‌888‌]

‌Meeeee 88‌ Meeeeeeeeeeeeee Meeeeeeeeee Meeeeeeeeee eeee Meeeeee–Meeeeeeeee–Meeeeeee Meeeeeeeeeeeee[‌888‌,‌888‌]

‌Meeeeeeeeee 88‌

M8	Meeee (%)	Mee
8-e-MeM8M8	88	[‌888‌]
8-Me(MM8)8M8M8	88	[‌888‌]
	88	[‌888‌]
	88	[‌888‌]
	88	[‌888‌]
	88	[‌888‌]
	88	[‌888‌]

Mee Meeeeee–Meeeeeeeee–Meeeeeee eeeeeeeeeeeee eee eeee ee eeeeeeeee eeee eeeeeeeee eeee eeee eee ee eeee eeeeeeeeeeeee eeeee eeeeee eee eeee eeeeeeee. Meee eeeeeee eeeeeeee eeeeeeeeeeeeee eee eeeee eeeeee ee eeeeeeee eeee eeeeee eeeeeee ee eeeeee eeeee; eeee, eeeeeeeeeeee ee eee eeeeeeee eeeeeeeee eeeeeeeeeee eeeeeeeeeeeee ‌888‌ (M8 = Me; e = 8) ee eee eeeeee eeeeeeeee ‌888‌ (M8 = Me; e = 8) eeeeee eee eeeeeeeeeee eee(eeeeeeeeeeeeeeee)eeeeeeee ‌888‌ (M8 = Me; e = 8) ee ‌888‌ (M8 = Me; e = 8). Mee eeeee ee eeeee eee eeeeeeee eee eeee ee eeeeeeeee eeee eee eeeeeeeeeeeee eeeeeeeeeeeee ‌888‌ (M8 = Me; e = 8) ee 88% eeeee, eeeeeee eee eeeeee eeeeeee eee eeeeeeeeeeeeeee ‌888‌ (M8 = Me; e = 8) ee 88% eeeee (‌Meeeee 88‌).[‌888‌] M eeee eeeeee eeeeee ee eeeeeeee eeee eee eeeeeeeee 8,8-eee(eeeeeeeeeeeeeeee)eeee-8,8,8,8-eeeeeeee ‌888‌ (M8 = MMMM; e = 8) ee eeeeeeeeee ee eeeeeeeee eeee eeeeeeeeeeee ee eeeeee ee −88 ee −88°M; ee eeee eeee eee eeeee ee eee eeeeeeeeeeeee ‌888‌ (M8 = MMMM; e = 8) ee 88% (‌Meeeee 88‌).[‌888‌]

‌Meeeee 88‌ Meeeee Meeeeeee eeee Meeeeee–Meeeeeeeee–Meeeeeee Meeeeeeeeeeeee ee Me(eeeeeeeeeeeeeeee)eeeeeeee[‌888‌,‌888‌]

Meeeeeee Meeeeee–Meeeeeeeee–Meeeeeee eeeeeeeeeeeeee eeeeeee eeeeeeeeee eee eeeeeeeeeeee ee eeeeee eeeeeeeeeee eee eeeeeeee eeeeeeeeee eeeeee-eeee eeeeeee eee eeeee e eeeeee eeeeeeee eee eee eeeeeeeee ee eeeeeeee eeeeeee eeeeeeee eeeeee eee eee eeeeeeeee ee eeeeee-eeee eeeeeeee.[‌8‌–‌8‌] M eeeeee ee eeeeeeee eee eeeeeeee ee ‌Meeeee 88‌ [eee eeee ‌Meeeee 88‌, Meeeeee ‌88.8.8.8.88‌, eee eeeeeeee ee Meeeeee–Meeeeeeeee–Meeeeeee eeeeeeeeeeeeee ee eeee eee(eeee-8,8-eeeeee) eeee eee eeee ee eeeeeeeeee ee eeeeeeeeeeeeee eeeeeeeeeeeee;[‌888‌,‌888‌] eee eeee Meeeeee ‌88.8.8.8.8‌]; eeee, eee eeeeeeeeeeee ‌888‌ eee ‌888‌ eee eeeeee eeee ‌888‌ eee ‌888‌ ee eeeeee ee ee. 88%.[‌888‌,‌888‌] Meee eee eeeeeeee eeeeeee ‌888‌ ee eeeeeeeee eeee eee eeeeeeeee ‌888‌ eeeee eeee eeee ee eeeeeeeeeeeee.[‌888‌]

‌Meeeee 88‌ Meeeeeeee ee Meeeeeee Meeeeeeeeeee ee Meeeeeee Meeeee eee Meeeee-Meee Meeeeeee[‌888‌,‌888‌]

Meeeeeeeeeee Meeeeeeee

8-(eeee-Meeeeeeeeeeeeeeeeee)-8,8,8-eeeeeeeeee (‌Meeee 88‌, Meeee 8):[‌888‌]

8.8 M MeMe ee eeeeee (8.88 eM, 8.88 eeee) eee eeeee eeeeeeee ee 8-(eeee-eeeeeeeeeeeeeeeeeee)-8-(eeeeeeeeeeeeeeee)eeee-8,8-eeeee (888 ee, 8.888 eeee) ee eee eeeeee (88 eM) eeeeeeeeee ee −88°M. Mee eeee eee eeeeeee ee −88°M eee 88 eee, eee eeee ee eee eeeeee ee ee eeee 88 eee. Me8M (88 eM) eee eee. ee MM8Me (88 eM) eeee eeeee eee eee eeeeeee eeeee eee eeeeeeeee, eeeeee eeee eeeee (8 × 88 eM), eee eeeee (MeMM8). Meeeeee eeeeeee eee eeeeeeeeeeee ee eee eeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee, eeeeee) eeeeeeee eee eeeee eeeeeeee ee e eeeeeeeee eee; eeeee: 888 ee (88%).

References