Preparation of Primary and Secondary Dialkylmagnesiums by a Radical I/Mg‐Exchange Reaction Using sBu2Mg in Toluene

Abstract The treatment of primary or secondary alkyl iodides with sBu2Mg in toluene (25–40 °C, 2–4 h) provided dialkylmagnesiums that underwent various reactions with aldehydes, ketones, acid chlorides or allylic bromides. 3‐Substituted secondary cyclohexyl iodides led to all‐cis‐3‐cyclohexylmagnesium reagents under these exchange conditions in a highly stereoconvergent manner. Enantiomerically enriched 3‐silyloxy‐substituted secondary alkyl iodides gave after an exchange reaction with sBu2Mg stereodefined dialkylmagnesiums that after quenching with various electrophiles furnished various 1,3‐stereodefined products including homo‐aldol products (99 % dr and 98 % ee). Mechanistic studies confirmed a radical pathway for these new iodine/magnesium‐exchange reactions.


SI3
List of substrates (1a-1i) described in scheme 2 and of the electrophiles used a) List of substrates (1a-1i) described in Scheme 2 b) Structure of the electrophiles used

Optimization of the Preparation of Primary Dialkylmagnesiums
[a] Reactions were performed on a 0.5 mmol scale. Yields were determined by GC-analysis using undecane SI10

Preparation of Primary and Secondary Dialkylmagnesiums via a Radical I/Mgexchange Reaction using sBu2Mg in Toluene Preparation of sBu2Mg solution in toluene 20
A dry and argon flushed 250mL Schlenk-tube, equipped with a magnetic stirrer and a septum, was charged with sBuMgCl (2 M in diethyl ether, 10 mL, 20 mmol). Then sBuLi (1.7 M in cyclohexane, 12 mL, 20 mmol) was added dropwise at room temperature. After the addition was complete, the reaction mixture was stirred for 1 h. The solvents were then removed under vacuum affording a greyish solid. Dry toluene was then slowly added under stirring. Then salts were allowed to precipitate (ca. 24 h) and the solution was filtered via syringe filter (30 mm with 0.45 μm glass fiber membrane) and transferred to a dry argon flushed Schlenk-tube. The concentration of the sBu2Mg was determined via titration with benzoic acid (70 mg in 2 mL THF) and 4-(phenylazo)diphenylamine as indicator.

Preparation of secondary dialkylmagnesiums via an I/Mg-exchange reaction using sBu2Mg in toluene (TP3)
A dry and argon flushed Schlenk-tube, equipped with a magnetic stirring bar and a septum was charged with the respective secondary alkyl iodide (0.50 mmol) and dry toluene (2.0 mL). Then a solution of sBu2Mg (0.60 mL, 0.30 mmol) was added via syringe at room temperature and the reaction was stirred for 2 h. After that the corresponding electrophile (0.40 mmol) was added dropwise at -20 °C and the reaction mixture was stirred until completion. The reaction mixture was quenched with an aq. sat. NH4Cl solution and extracted with ethyl acetate (3×50 mL). The organic phase was then dried over Na2SO4, filtered and concentrated in vacuo. The crude product was subjected to column chromatography purification on silica yielding the corresponding product.
After the exchange was complete (4 h was added, and the reaction mixture was allowed to warm to room temperature in 1 h.
After the exchange was complete (4 h), 3-iodo-2-cyclohexen-1-one (67 mg, 0.30 mmol) was added at 0 °C and the reaction mixture was allowed to warm to room temperature in 1 h. [a] The reactions were performed on a 0.5 mmol scale. Yields were determined by GC-analysis using undecane (C11H24) as an internal standard.
[c] The reaction was performed in the presence of 1 equiv of additive.
[d] The reaction was performed in the presence of 3 equiv of additive.

Reaction with the cyclic iodo-acetal 12 in the presence of styrene
[a] The reaction was performed on a 0.5 mmol scale. Yield was determined by GC-analysis using undecane (C11H24) as an internal standard.