Iron-catalyzed sequential hydrosilylation

Abstract

Highly regio-, diastereo- and enantioselective iron-catalyzed sequential hydrosilylation of o-alk-n-enyl-phenyl silanes with alkynes is reported for various 5-, 6-, and 7-membered benzosilacycles in 60-94% yields with up to 95:5 rr, 95:5 dr, and 99% ee. Chiral fully carbon-substituted silicon-stereogenic benzosilacycles could also be obtained via triple hydrosilylation reactions. The unique electronic effect of ligands is observed while adjusting the regioselectivity and enantioselectivity in hydrosilylation reactions. A possible mechanism has been proposed by variable time normalization analysis (VTNA) and H/D exchange experiment.

Fig. 1. Benzosilacycles and their synthesis.

A Silasubstitution strategy, B Metal-catalyzed construction of benzosilacycles, C This work: Construction of 5-, 6-, 7-membered benzosilacycles by iron catalysts. The green colour is about the construction of 5-membered benzosilacycles, blue colour is aboult the construction of 6-membered benzosilacycles and purple colour is about the construction of 7-membered benzosilacycles. The pink colour is about “Si”.

Fig. 2. The scope of 2-vinylphenyl silanes and 2-allylphenyl silanes.

^aStandard conditions: 1a (0.60 mmol), 2a (0.50 mmol), cat. Fe-3 (0.025 mol), LiOtBu (0.075 mmol), toluene (1 mL). ^bStandard conditions: 4a (0.3 mmol), 2a (0.3 mmol), cat. Fe-4 (0.015 mmol), LiOtBu (0.045 mmol), toluene (0.6 mL). ^cStandard conditions: 4a (0.30 mmol), 2a (0.30 mmol), cat. Fe-5 (0.015 mmol), LiOtBu (0.045 mmol), toluene (0.6 mL). ^dIsolated yield in the parentheses. ^eYields were determined by ¹H NMR using TMSPh as an internal standard. A The scope of 2-vinylphenyl silanes; B The scope of 2-allylphenyl silanes.

Fig. 3. The scope of chiral benzosilacycles.

^aStandard conditions: 7a (0.50 mmol), cat. Fe-5 (0.010 mmol), NaBHEt₃ (0.030 mmol). ^bStandard conditions: 7a (0.30 mmol), cat. Fe-5 (0.006 mmol), NaBHEt₃ (0.018 mmol), cat. Fe-3 (0.015 mmol), 2a (0.30 mmol), LiOtBu (0.045 mmol), toluene (0.6 mL). ^cStandard conditions: 11a (0.30 mmol), L (0.006 mmol), NaBHEt₃ (0.018 mmol), THF (0.6 mL). ^dStandard conditions: 7a (0.36 mmol). ^eYields were determined by ¹H NMR using TMSPh as an internal standard. ^fIsolated yield in the parentheses. A The scope of benzosilacycles with two Si–H bonds; B The scope of benzosilacycles with vicinal chiral carbon and silicon-centers; C The scope of 7-membered benzosilacycles.

Fig. 4. Gram scale reaction and further derivatization.

^aeq.1 Gram scale reaction of 1a, ^beq.2 Gram scale reaction of 7a, ^ceq.3 further derivatization of 3a, ^deq.4-6 further derivatization of 10a. A. Gram scale reaction of 1a and 7a. B further derivatization of 3a and 10a.

Fig. 5. Mechanistic experiments to explore the active intermediate.

eq.7-8 Deuterium-labeling experiments.

Fig. 6. variable time normalization analysis.

a–c VTNA analysis of catalyst, d-f VTNA analysis of silane, g–i VTNA analysis of alkyne.

Fig. 7. The proposed mechanism in sequential hydrosilylation.

The proposed mechanism starts from intramolecular hydrosilylation, followed by intermolecular hydrosilylation.

Fig. 8. The primary models to predict the regiochemical outcome^a.

A–H The primary models to predict the regiochemical outcome to explain the selectivity in the construction of 5- and 6-membered benzosilacycles.