Science of Synthesis

Hopkinson, M. N.; Gouverneur, V., Science of Synthesis Knowledge Updates, (2011) 2, 111.

Hypervalent iodine(III) reagents are known to undergo rapid oxidative addition to palladium complexes[‌62‌] and could be expected to be superior to organic halides as substrates for gold-catalyzed cross-coupling reactions. Treating the alkynyliodine(III) reagent ‌24‌ with indole in the presence of gold(I) chloride (5 mol%) in dichloromethane affords 3-[(triisopropylsilyl)ethynyl]indole (‌25‌, R1 = H) in 65% yield as the only product (‌Scheme 12‌).[‌63‌] This compound results from a direct alkynylation process involving C(sp2)–H bond functionalization at the 3-position of indole. Performing the reaction in diethyl ether (0.05 M) results in an increase in the yield of ‌25‌ (R1 = H) to 86%. Importantly, other metals including palladium(0) do not catalyze this process, implying that the observed reactivity is not due to other transition-metal contaminants in the reagents.[‌60‌] The alkynylation process can be applied to a range of diversely substituted indoles, affording the corresponding silylated alkynes in good yields. Unlike alternative Sonogashira alkynylation procedures catalyzed by palladium, this process can be performed with bromo and iodo substituents on the heterocycle with no loss of the halogen functionality. 3-Methylindole, with a blocked 3-position, undergoes alkynylation at the 2-position to give ‌26‌ in 76% yield. The process can also be performed with free or N-protected pyrroles affording either the 2-alkynyl or 3-alkynyl products, e.g. ‌27‌ or ‌28‌, respectively, depending on the nature of the substituent on nitrogen. Whilst thiophenes are unreactive under these conditions, the addition of trifluoroacetic acid (1.2 equiv) to the reaction mixture in acetonitrile (0.2 M) allows for the analogous preparation of 2-alkynyl- or 3-alkynylthiophenes such as ‌29‌ and ‌30‌, respectively, in moderate to good yields. These compounds have found extensive use as organic materials.[‌64‌]

‌Meeeee 88‌ Meeeeeeeeeee ee Meeeeee, Meeeeeee, eee Meeeeeeeee eeee ee Meeeeeeeeeeee(MMM) Meeeeee[‌88‌,‌88‌]

‌Meeeeeeeeee 88‌

Mee eeeeeeeeeee eeeeeeee eee eeeeeeeee eee eee eeeeee eeeeeeeeeeee eeeeeee (‌Meeeee 88‌). Mee eeeee eeee eeeeeeee e eeee(M)/eeee(MMM) eeeee eeeee. Meeeeeeee eeeeeeee ee eee eeeeeeeee­eeee(MMM) eeeeeee ‌88‌ ee eeee(M) eeeee eeee ee eee eeeeeeeeeee(MMM) eeeeeee ‌88‌. Meeeeee–Meeeee-eeee eeeeeeeeeeeeeee ee eeee eeeeeee eeeeeee e eeeeeeeeeeee(MMM) eeeeeee eeeee eeeee eeeeeee eee eeeee-eeeeeee eeeeeee eee eeeeeeeeee eeee(M) eeee eeeeeeeee eeeeeeeeeee. Me eee eeeeee eeee, eee eeee(M) eeeee eee ee e π-eeee, eeeeeeeeee eee eeeeeeeee eeeeee ee eeeeeeeeeeee eeeeee ee eee eeeeeeeeeee. Meee eeee eeeee eeee ee eee eeeeeeeee(M) eeeeeee ‌88‌, eeeee eeeee eeeeeee e β-eeeeeeeeeee ee eeeeeeee eee eeeeeee eee 8-eeeeeeeeeee eeee. Meeeeeeeeeeee, eee eeeeee eeeeeeeee eeeee eeee ee eee eeeee eeeeeeeee(M) eeeeeeeeeee ‌88‌, eeeee eeeee eeeeeee eee eeeeee eeeeeee eeee α-eeeeeeeeeee eeeeeeee ee e 8,8-eeeee. Meee ee eeeee eeeeeeeeeee eeeeeee eee eeeeeeee ee eeeeeeeeeee eeeeeee eeeee eee eeeeeeee. Mee eeee ee eee eeeeeeeeeeeeeee eeee eeeeeeee ee eee eeee ee eeeeeeeeee ee eeee eee eeeee eeeeeeeeee.

‌Meeeee 88‌ Meeeeeeee Meeeeeeeee ee Meeeeeeeeee Meeeeeeeeeee[‌88‌,‌88‌]

Meeeeeeeeeee Meeeeeeee

[(Meeeeeeeeeeeeeeee)eeeeeee]eeeeeee eee -eeeeeeee ‌88‌–‌88‌; Meeeeee Meeeeeeee:[‌88‌]

MMMMMMM: Meeeee(MMM) eeeeeeee eee eeeeee eeeeeeee.

Meeeeeeeeeeee(MMM) eeeeeee ‌88‌ (888 ee, 8.888 eeee, 8.8 eeeee) eee eeeee ee e eeeeeeee eeee ee MeMe (8.8 ee, 8.888 eeee, 8.88 eeeee) eee eee eeeeeeeeeeeee eeeeee ee eeeeeee (8.888 eeee, 8.8 eeeee) ee Me8M (8 eM) eeeee eee. Mee eeeeee eee eeeeee eee eee eeeeeee eee eeeeeee ee ee eee 88–88 e. Me8M (88 eM) eee eeeee eee eee eeeeeee eeeee eee eeeeee eeee 8.8 M ee MeMM (8 × 88 eM). Mee eeeeeee eeeeee eeee eeeeeeee eee eeeeeeeee eeee Me8M (88 eM). Mee eeeeeee eeeeee eeee eeeeeeee, eeeeee eeee eee. ee MeMMM8 (88 eM) eee eeeee (88 eM), eeeee (MeMM8), eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee.

8-Meeeee-8-[(eeeeeeeeeeeeeeeee)eeeeeee]eeeeeeeee (‌88‌); Meeeeee Meeeeeeee:[‌88‌]

Me e eeeeeeee eeee ee MeMe (8.8 ee, 8.888 eeee, 8.88 eeeee) ee MeMM (8 eM) eee eeeee 8-eeeeeeeeeeeeeee (88 μM, 8.88 eeee, 8 eeeee) eeeee eee. Meeee 8 eee, MMM (88 μM, 8.88 eeee, 8.8 eeeee) eee eeeeeeeeeeeee(MMM) eeeeeee ‌88‌ (888 ee, 8.888 eeee, 8.8 eeeee) eeee eeeee. Mee eeeeee eee eeeeee eee eee eeeeeee eee eeeeeee ee ee eee 88 e. Me8M (88 eM) eee eeeee, eee eee eeeeeee eeeee eee eeeeee eeee 8.8 M ee MeMM (8 × 88 eM). Mee eeeeeee eeeeee eeee eeeeeeee eee eeeeeeeee eeee Me8M (88 eM). Mee eeeeeee eeeeee eeee eeeeeeee, eeeeee eeee eee. ee MeMMM8 (88 eM) eee eeeee (88 eM), eeeee (MeMM8), eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Meeeeeeeeeee ee eeeee eeeeeeeeeeeeee (eeeeee eee, eeeeeee) eeeeeeee e eeeeeeeee eee; eeeee: 88 ee (88%).

References