Science of Synthesis

Lee, D.; Reddy Sabbasani, V., Science of Synthesis: Metal-Catalyzed Cyclization Reactions, (2016) 2, 655.

Ring-closing metathesis is a powerful tool to form various cyclic frameworks, yet diene ring-closing metathesis provides a mixture of E- and Z-isomers with unpredictable ratios except for small- and medium-sized rings where Z-isomers are preferred. In macrocyclic ring-closing metathesis, usually E-isomers form more favorably due to the equilibrium nature of the metathesis process although complete stereocontrol is yet to be realized. In contrast, achieving Z-selective metathesis has been an outstanding problem in macrocyclic ring-closing metathesis. However, several successful processes including catalyst-based control have been developed recently (see Section ‌2.10.2.2.2.2‌). In this regard, ring-closing alkyne metathesis to construct macrocycles containing an alkyne moiety followed by semireduction would be an attractive solution for the stereoselective synthesis of E- or Z-alkene-containing macrocycles (‌Scheme 127‌). From ring-closing alkyne metathesis products, Z-configured cycloalkenes can be synthesized by semihydrogenation with Lindlar catalyst. Alternatively, Birch reduction, trans hydrosilylation–desilylation, and trans hydroboration–protodeborylation lead to the corresponding E-alkene-containing macrocycles.

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‌Meeeee 888‌ Meee-Meeeeee Meeeee Meeeeeeeee–Meeeeeeeeeeeeeeee eee eee Meeeeeeeeee ee M-Meeeee-Meeeeeeeee Meeeeeeeeee[‌88‌,‌888‌]

Mee eeee-eeeeeee eeeeee eeeeeeeeee ee eeeee ‌888‌ eeeeeeeeee e eeeeeeeee eeeeeeee eeeeee eeeeee eeee eee Meeeeeee eeeeeeeee eeeeee eeeeeeeeee ee eeeeeeeeeeeeeeeeeeeeee(8) eee 8-eeeeeeeeeeee ee Meeeeee eeeeeeee ‌8‌ eeeeeeee eeeeeeeeeee eeeeee ‌888‌ ee eeee eeeeee (‌Meeeee 888‌). Meeeeeeeeeeeeeeee ee ‌888‌ eeeee M-eeeeeeeeee eeeeeeeeee ‌888‌, eeeee ee eeeeeeeeee ee eeeeeeeeeeee M (‌888‌).[‌888‌]

‌Meeeee 888‌ Meee-Meeeeee Meeeee Meeeeeeeee–Meeeeeeeeeeeeeeee Meeeeeee ee eee Meeeeeeee ee Meeeeeeeeeee M[‌888‌]

‌Meeeeeeeeee 888‌

M eeee-eeeeeee eeeeee eeeeeeeeee–eeeeeeeeeeeeeeeee eeeeeeee ee eeee eee e eeeeeeeeeeeeeee eeeeeeeee ee MMM8–8,88-eeeeeee (‌888‌) (‌Meeeee 888‌).[‌888‌] Me eeee eeeeeeeee, ee ee eeee eeeeeeeee eeeeeeeeee eeeeeeee eeeeeee, eeeeee eeee eee eeeeeeeeee(MMM) eeeeeeeee ‌888‌ ee eeeeeeeeeeeeeee, eeeeeeee eeeeeeee eeeee ‌888‌ eeee eeeeeeeeeee eeeeee ‌888‌ ee eeeeeee ee 88 °M. Meeeeeeeeeeeeeeee ee ‌888‌ eeeeeeee ee eeeeeeeeeeeeeeeee eeeeeee MMM8–8,88-eeeeeee (‌888‌).

‌Meeeee 888‌ Meee-Meeeeee Meeeee Meeeeeeeee–Meeeeeeeeeeeeeeee ee eee Meeeeeeee ee MMM8–8,88-Meeeeee[‌888‌]

M eeeeeee eeeeeeee ee eeeeeeee ee eee eeeeeeeee ee eeeeeeeeee M (‌88‌) (‌Meeeee 888‌), eeeee eee eeeeeeeeeee eeeeee ‌888‌ ee eeeeeeee ee eeee-eeeeeee eeeeee eeeeeeeeee ee eeeee ‌888‌ eeee eeeeeeeeee eeeeeee ‌888‌. Meeeeeeeeeeeeeeee ee eee eeeeeeeeeee eeeeee ‌888‌ eee eeeeeeeeeeeeeeeee eeeeeeeee eee eeeeeeeee ee eeeeeeeeee M (‌88‌).[‌888‌] Meee eeeee eeee-eeeeeee eeeeeeeeee eeeee eeeeeeee eee eeeeeeeeee M (‌88‌) eeeeeeee eeeeeeeee eeee eeee ee eee eeeeeeee-eeeeeeeeee M-eeeeeeeee eeeee eeee-eeeeeee eeeeeeeeee eeeeeeeee ee ‌Meeeee 88‌ (Meeeeee ‌8.88.8.8.8.8‌).

‌Meeeee 888‌ Meee-Meeeeee Meeeee Meeeeeeeee–Meeeeeeeeeeeeeeee ee eee Meeeeeeee ee Meeeeeeeee M[‌888‌]

M eeeeeeeee ee eeeeeeeeee M (‌888‌) eeeeee ee e eeee-eeeeeee eeeeee eeeeeeeeee–eeeeeeeeeeeee eeeeeeee eee eee eeeeeeeeeeeeeee eeeeeeeeeeee ee eee M-eeeeeeeeee eeeeee eeee ee eee eeeeeeeee. Mee eeee-eeeeeee eeeeee eeeeeeeeee ee eeeee ‌888‌ eeeeeeeee ee eeeeeeee–eeeeeeeeee eeeeeee ‌8‌ ee eeeeeee ee 88 °M eeeeeeee eeeeeeeeee ‌888‌ ee 88% eeeee (‌Meeeee 888‌).[‌888‌,‌888‌] Meeeeeeeeee eeeeee ‌888‌ ee eeeeeee eeeeeeeeee ee eeeeeeeeeee eeeeeeeeeeee ‌888‌, eeeee ee eeeeeeeeeeeeeeeee eeeeeeeeeeee ee eee eeeeeeeeeeeee M-eeeeeeeeee eeeeeeeeeee eeeeeee eeeeeee eeeeeeeeee M (‌888‌). Meeeeee eeeeeeeee ee eeeeeeeeee M (‌888‌) eeee eeeeeee e eeee-eeeeeee eeeeee eeeeeeeeee–eeeeeeeeeeeeeeeee eeeeeeee ee eeeeeee eee eeeeeeeeeee M-eeeeee eeeee eeeeeeeeee eeeeeee ‌888‌ ee eeeeeeee,[‌888‌] eee e eeeee eee eeee e eeeeeeeeee eeeeeee eeeeeeee eee eee eeee-eeeeeee eeeeee eeeeeeeeee.[‌888‌] Meeee eeeee eeee-eeeeeee eeeeee eeeeeeeeee eeeee eeeeeeeee ee eeeeeeeeee M (‌888‌) eeeeeeeee eeeeeee eeee eee eeeee eeee-eeeeeee eeeeeeeeee eeeee eeeeeeee eeeeeeeee ee ‌Meeeee 88‌ (Meeeeee ‌8.88.8.8.8‌).

‌Meeeee 888‌ Meee-Meeeeee Meeeee Meeeeeeeee–Meeeeeeeeeeeeeeee ee eee Meeeeeeee ee Meeeeeeeee M[‌888‌]

M eeeee eeeeeeeee ee eeeeeeeeeeeeeee M (‌888‌) eee M (‌888‌) ee eeeee ee eee eeee-eeeeeee eeeeee eeeeeeeeee–eeeeeeeeeeeeeeeee eeeeeeee ee eee eee eeee (‌Meeeee 888‌).[‌888‌] Meeeeee eeeeee ee eee eeee-eeeeeee eeeeee eeeeeeeeee ee eeeeee ‌888‌ eee ‌888‌ eeeee eee ee eeee eeeeeeeee eeeeeeee eeee eeeeeeeeeeeeeee eee eeeeeeeeee(MMM) eeeeeeeee ‌888‌ eeeeeeee eeeeeeeeeeeeee eeeeeee eeee ee eeee eeeeeeee eeeeeeee.[‌888‌] Meeeeeeeeee, eee eeeeeeee eeee eeeeeeee–eeeeeeeeee eeeeeee ‌8‌ eeeee eeeeeeeeee eeeeeeee eee ee eee Meeee eeeeeee.[‌888‌] M eeeeeeeeeeeeeeeee eeeeeeee eeeeeeeeee eeeeeee eeeeeeeeeee ee eeee eeeeeeeeee eee ee eee eeeee eeeeeeeeee ee eee eeeeeee eeeeeeee ee eeeee eeee eeeeeeee.[‌888‌] Me eee eeeee eeee, eee eeeeeeee eeee eeeeeeeeee eeeeeee ‌888‌ eeeeeeee eeeeeeee eee eeeeeeeeeee eeeeeee ‌888‌ eee ‌888‌, eeeee eee eeeeeee eeeeeeeeeeeeeeee ee eeee M-eeeeeee eeeeeeeeeee eeeeeee eeeeeeee eeeeeeeeeeeeeee M (‌888‌) eee M (‌888‌), eeeeeeeeeeee.

‌Meeeee 888‌ Meee-Meeeeee Meeeee Meeeeeeeee–Meeeeeeeeeeeeeeee eee eee Meeeeeeee ee Meeeeeeeeeeeeee M eee M[‌888‌]

Mee eeeeeee ee eee eeee-eeeeeee eeeeee eeeeeeeeee–eeeeeeeeeeeeeeeee eeeeeeee ee eeeeeee eeeeeeeeeeee ee eee eeeee eeeeeeeee ee eeeeeeeeeee M (‌888‌) (‌Meeeee 888‌).[‌88‌,‌888‌] Meeeeeeeeee eeee-eeeeeee eeeeee eeeeeeeeee ee eeeeeeeeee eeeeeeeeeee eeeee ‌888‌ eeeeee eeeeeeee eeee Meeeeee eeeeeeeeee ‌8‌ (88 eee%, eeeeeeeeeeeee) ee eeeeee eeeeeeeeeee ‌888‌ ee 88% eeeee. Mee eee eeeeee eeee ee eee 88-eeeeeeee eeee ee eeee eeeeeeeee ee eeeeeeeeeeeeeeeee ee eeeeeeee ‌888‌. Meeeeeeeee eeeeeeeee ee eeee eeeeee eeeeeeee ee eeeee-eeeeeeee-eeee eeeeeeeee (eeeee eeee-eeeeeee eeeeeeeeee eeee Meeeeeʼ eeeee-eeeeeeeeee eeeeeeee ‌88‌) eeeee ee e eeeee eeeeeeeee ee eeeeeeeeeee M (‌888‌).[‌888‌] Me eeeeeeeeee, eee 88-eeeeeeee eeeeee M-eeeeee ee eeeeeeeeeee M (‌888‌) eee eeee ee eeeeeeeee ee eeeee eeee-eeeeeee eeeeeeeeee. Meee M eeeeeeeeeee ee eeee eeeeeeee eeeee eeeeeeee eeeeeeeee eeeeeeee–eeeeeeeeee eeeeeeeee eeee ee ‌88‌.[‌88‌] Meee, eeeeeeeee ee eeeeeeeee ‌888‌ eeee eeeeeeee eeeeeeee ‌88‌ (8 eee%) eeeeeee eeeeeeeeeee M (‌888‌) ee 88% eeeee eeee e 88:8 M/M eeeee.[‌88‌] Meeeeee eeeeeeee ee eeeeeeee eee eeeeeeeee eeeeeee ee eeeeee eeee eee eeeeeeee eeeeee ee eeeee e eeeeee-eeee eeeeeeeeeeeee eeeeeeee ee eee eeeeeeee–eeeeeeeeeee eeeeeee. Meeeeeee eeee eeeeeee eeeeeeeeeeee eee eeeeeeeeeee eeeee ee eee M-eeeeeeeee eeee-eeeeeee eeeeeeeeee eeeeeeee, eeeeeeeee eeeeeeeeeeee ee eeeeeeee eeeeeeeeee eee eeee eeeeeeeeee ee eeeeeeeee ee eeeeeee eeee eeeeeeeee eeeeeeeeee eeeee eeeeeeeeeee eeee M eeeeeeeeeee.

‌Meeeee 888‌ Meeeeeeeee ee Meee-Meeeeee Meeeee Meeeeeeeee–Meeeeeeeeeeeeeeee eeee Meeee Meee-Meeeeee Meeeeeeeee eee eee Meeeeeeee ee Meeeeeeeeee M[‌88‌,‌888‌]

References