Science of Synthesis

Bietti, M.; Dénès, F., Science of Synthesis: Free Radicals: Fundamentals and Applications in Organic Synthesis, (2021) 1, 542.

In 1994, the Kita group reported the direct azidation of 4-alkylanisoles using [bis(trifluoroacetoxy)iodo]benzene and azidotrimethylsilane.[‌175‌] Later, in 2001, Bols and Viuf reported the azidation of activated C—H bonds (typically benzyl ethers), using iodine azide (IN3) in refluxing acetonitrile.[‌176‌] Owing to the weak I—N3 bond, homolytic cleavage leading to the azidyl radical N3• is easily achieved upon heating. The azidyl radical can then play the role of a HAT reagent [BDE(H—N3) = 93.3 kcal · mol−1][‌177‌] for activated C—H bonds (‌Scheme 66‌). A disadvantage of this reaction is the requirement for an excess of iodine azide, a hazardous and explosive reagent, particularly as a solid. The Bols group later reported safer conditions with the use of 1.3–4 equivalents of the azidotrimethylsilane/(diacetoxyiodo)benzene combination to produce in situ the corresponding azidoiodinane reagent.[‌178‌] The procedure gives similar yields to those obtained with iodine azide but can be carried out under milder (and thus safer) conditions (25 °C). The addition of the azidyl radical to alkenes is sometimes observed as a side reaction. With the use of more reactive reagents or modified conditions, the range of C—H bonds that can participate in the azidation reaction can be extended to include aliphatic C—H bonds (see Section ‌1.12.6.1.3‌).

‌Meeeee 88‌ Meeeeeee M—M Meee Meeeeeeee eeee Meeeee Meeee[‌888‌]

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‌Meeeee 88‌ Meeeeeeee ee Meeeeeeeeee eee Meeeeeeeeeee(M)-Meeeeeee M—M Meee Meeeeeeeee[‌888‌]

Meeeeeeeeeeee, ee eeeee-eeeeeeee eeeeeeee ee eeeeee eeee eeee eeeeee eee, eeeee eeeee eeeeeeeeee, eee eeeee ee eeeeee eeeeeeeeee eeee eee eeeeeeeee eeeeeee eee eeeeee eeeeeeee. Mee eeeeeee eeeeeeeee eee eeeeeeee eeeeeeeeeeee(M) eeeeeee, eeeee ee eeeeeeeeeee eee MMM eeee eee eeeeeeeee (‌Meeeee 88‌). Mee eeeeee-eeeeeeee eeeeeee eee eee eeeeeeeeeeeeee(MM) eeeeeeeeeeee eeeeee eeeee eee MMM eeee eeeeeeeee ee eeee eee eeeeeeeee eeeeeee. Meeeeee ee ee eeeeeeeee ee eeeeeeee eee eeeeeeeeeeeee eeee eee eeeeeee eeeeee (“eeeeee eeeeeee” eeeeeeeee), eee eeeeeeeee eeeeeee ee eeeeeee eeeeeeee ee eeee ee e eeeeeee eeee eee eeeeeee eeeeeeeee eeee eeeeeeeeeeeee ee eee M—M eeee, eeee eeeeee e eeeeee eeeeeeeeeee eee eee eeeeeeeee eeeeeee ee eeeeeee eeeeeeee (eeeeeeeee ee eee 8:8 ee 8:8 eeeee). Mee eeeeee eeeeeeeeeeee eeee eeeeeeeeee-eeeee eeeeeeeee eee eeeeee eee eee eeeeeeeeeeeeeeeee ee eeeeeee eeeeeee eeeeeeee eee eeeee (e.e., eeeeeeeeee, eeeeeeeee, eeeeeeeeeee, eeeeeeeeeee). Me ee eeeeeeee eeeee ee eee eeeeeeeeeeee ee ee eeeeeeeeeeeeee(MM) eeeeeeeeeeee ee eee eeeeeeeee ee eeee eeeeeeeeeeeeee, eee eeeeeeeee ee eeeeeeeeeee eeee e eeeeee eeeeeeeee–eeeee eeeeeeee eeeee eee eeeee eeeeeee ee 88% eeeeeeeeeeee eeeeee.[‌888‌]

‌Meeeee 88‌ Meeeeeee Meeeeeeee eee eee M—M Meee Meeeeeeee Meeee Meeeeeeeeeee(M) Meeeeeeee[‌888‌]

Me 8888, Mee ee ee. eeeeeeee e eeeeee(M)-eeeeeeeee M—M eeeeeeeee ee β,γ-eeeeeeeeeee eeeeee eee eeeeee eeeeeeeeeee eeeeeeeeeee.[‌888‌] Mee eeeeeeeee (8.8–8.8 eeee eeeee) ee eeeeee ee eeeeeeeeee eee 88 eeeee ee 88 °M, ee eee eeeeeeee ee eeeeee(M) eeeeeeee (8 eee%) eee eeeeeeeeeeeeeeeee (8 eee%), eeee eeee eeeeeeee ee 8,8-ee-eeee-eeeeeeeeeeeeeee-8-eee (8 eeeee) ee e eeeeeeee eeeeee (‌Meeeee 88‌). Meeee eeeee eeeeeeeeee, eee eeeeeeeee eeeeeeee eeeeeee eeeeeeeeeee ee eeee eeeeeeeeee.[‌888‌]

‌Meeeee 88‌ Meeeeeeee ee Meeeeeeeee[‌888‌]

‌Meeeeeeeeee 88‌

Mee eeeeee(M) eeeeeeee eeeeeeeeee eeeeeee eee M—M eeee ee 8,8-ee-eeee-eeeeeeeeeeeeeee-8-eee ee eeee ee eeeeee-eeee eeeeeee, eee eeee ee eeeee eee ee ee eeeeeeee e eeeeeeee eeee eeee eee eeeeeeeee eeeeeeee (ee eeeeeee) eeeeeeee (‌Meeeee 88‌). Mee eeeeeeeee eeeeee-eeeeeeee eeeeeee eeeeeee eeee eee eeeeee(MM) eeeeeee eee, eeeeeeeee eeeeeeeee eeeeeeeeeee, eee eeeeeeeee eeeeeee ee eeeeeeee, eeeeeeee eeee eee eeeeeeeeeeee ee eee eeeeee(M) eeeeeeee eeeeeeee. Meeeeeeeee eeeee eeeeeeeeeee eeee eee eeeeeeee eeeee eeeeeeeeee eeeee ee eee eeeeeeeee. Meeee eeeee eeeeeeeeee, eeeeeeeeeee eeeeeeeee eeeeee eee eee eeeeeeee eeeeeeee eee eeee eeeeeeee eeeeeeee.

‌Meeeee 88‌ Meeeeeee Meeeeeeee eee eee Meeeeeeee ee Meeeeeeeee eeee Meeeee Meeeeeeeeee Meeeeeeeeee[‌888‌]

Meeee ee ee. eeeeeeee e eeee eeeeeeeee ee 8888 eee eee M—M eeeeeeeee ee eeeeeee, eeeeeeee, eee eeeeeeeee M—M eeeee eeeee eeee eee eee ee M-eeeeeeeeeeeeeeeeee (88 eee%) eee e eeeeeee eeeeeeeeeeeeeeee (8.8–8 eeeee).[‌888‌] Mee eee ee eee(8,8,8-eeeeeeeeeeeeee) eeeeeeeeeeeeeeee ee e eeeeeee eeee eeeeee eee eeeeeeeeeee ee eeeeeee eeee eee eeeeeeee ee eee M—M eeee eee eee eeeeeeeeeeee ee eee eeeee ee eeeeeeee eee eeeeeeeee eeeeee eeeeeeeee eeee eeee eee eeeeee eeee ee eeeeeee (‌Meeeee 88‌).

‌Meeeee 88‌ M-Meeeeeeeeeeeeeeeee-Meeeeeee Meeeeeeee ee e Meeeeeee M—M Meeeeeee[‌888‌]

Me eeee eeeeeeeee, eee-eeeeeeee eeeeeeeee ee M-eeeeeeeeeeeeeeeeee ee e eeeeeee eeeeeeeeeeeeeeee ee eeee ee eeeeeeee eee eeeeeeeeeeeee eeeeeeeeeee M-eeee eeeeeee, eee eeee ee eeeee ee ee eeeeeeee eee eeeeee-eeeeeeee eeeeeee ee MMM. Mee eeeeee-eeeeeeee eeeeeee ee eeee eeeeeee eeee e eeeeeee eeeeeeeeeeeeeeee eee eee eeeeeeeee eeeeeeeeeeeee eeeeeeeeee-eeee eeeeeee eeeeeeeee e eeeeeeee eeee, eeeeeeeeee eeee M-eeeeeeeeeeeeeeeeee, ee eeeeeee eee eeeeeeeee eeeeeeeeee eee eeeeeeeeee eee eeeeeeeeeee M-eeee eeeeeee. Meee eeeeeeeeeee eeeeeeeeeee ee eee eeeeeee eeeee, eeeeeeee eee eee ee M-eeeeeeeeeeeeeeeeee ee eeeeeeeeeeeeeeeee eeeeeeeeee. Meeeeeeeeeee, e eeeeeeee eeeee ee eeeeee ee eeeeeeeee ee eeeeeeee ee eee eeeeeeeee ee eee eeeeeeeeeee eeeeee ee ee eeeeeeeeeeeeeee eeeeeeee eeeeeeeee (88% eeeeeeeee ee eeeeeeeeeeeee).

Mee eeeeeee eeeeeeeee ee eeeeeeeeeee eeeeeeeee eeeeeeee eeee eeeeeeee eeeee eeeeee, eeeeee eeeeee ee eeeeeeeeee eee eeeeeeeeeeeeeee (‌Meeeee 88‌).[‌888‌]

‌Meeeee 88‌ M-Meeeeeeeeeeeeeeeee-Meeeeeee Meeeeeeee ee e Meeeeeeeeee M—M Meeeeeee[‌888‌]

‌Meeeeeeeeee 88‌

References