Preparation of Primary and Secondary Dialkylmagnesiums by a Radical I/Mg-Exchange Reaction Using sBu(2)Mg in Toluene

The treatment of primary or secondary alkyl iodides with sBu(2)Mg in toluene (25-40 degrees 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 sBu(2)Mg 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

Iron-Catalyzed Radical Zincations of Alkyl Iodides

We report a new iron-catalyzed I/Zn-exchange allowing to convert primary or tailored secondary alkyl iodides into the corresponding alkylzinc iodides. In the presence of a remote double bond at position 5, diastereoselective ring closures are observed. Quenching of these zinc reagents, after transmetalation to copper species (with CuCN center dot 2LiCl) or under Pd-catalysis, with typical electrophiles (allyl bromides, acid chlorides or aryl iodides) gave various polyfunctional products

Transition‐Metal Free Electrophilic Aminations of PolyfunctionalO‐2,4,6‐Trimethylbenzoyl Hydroxylamines with Zinc and Magnesium Organometallics

We reported a new electrophilic amination of various primary, secondary and tertiary alkyl, benzylic, allylic zinc and magnesium organometallics with O-2,4,6-trimethylbenzoyl hydroxylamines (O-TBHAs) in 52–99 % yield. These O-TBHAs displayed an excellent long-term stability and were readily prepared from various highly functionalized secondary amines via a convenient 3 step procedure. The amination reactions showed remarkable chemoselectivity proceeding without any transition-metal catalyst and were usually complete after 1–3 h reaction time at 25 °C. Furthermore, this electrophilic amination also provided access to enantioenriched tertiary amines (up to 88 % ee) by using optically enriched secondary alkylmagnesium reagents of the type s-AlkylMgCH2SiMe3

Exploiting Coordination Effects for the Regioselective Zincation of Diazines Using TMPZnX⋅LiX (X=Cl, Br)

A new method for regioselective zincations of challenging N-heterocyclic substrates such as pyrimidines and pyridazine was reported using bimetallic bases TMPZnX⋅LiX (TMP=2,2,6,6-tetramethylpiperidyl; X=Cl, Br). Reactions occurred under mild conditions (25-70 °C, using 1.75 equivalents of base without additives), furnishing 2-zincated pyrimidines and 3-zincated pyridazine, which were then trapped with a variety of electrophiles. Contrasting with other s-block metalating systems, which lack selectivity in their reactions even when operating at low temperatures, these mixed Li/Zn bases enabled unprecedented regioselectivities that cannot be replicated by either LiTMP nor Zn(TMP)2 on their own. Spectroscopic and structural interrogations of organometallic intermediates involved in these reactions have shed light on the complex constitution of reaction mixtures and the origins of their special reactivities

Reliable Functionalization of 5,6-Fused Bicyclic N-Heterocycles Pyrazolopyrimidines and Imidazopyridazines via Zinc and Magnesium Organometallics

DFT-calculations allow prediction of the reactivity of uncommon N-heterocyclic scaffolds of pyrazolo[1,5-c]pyrimidines and imidazo[1,2-b]pyridazines and considerably facilitate their functionalization. The derivatization of these N-heterocycles was realized using Grignard reagents for nucleophilic additions to 5-chloropyrazolo[1,5-a]pyrimidines and TMP2Zn center dot 2MgCl(2)center dot 2LiCl allowed regioselective zincations. In the case of 6-chloroimidazo[1,2-b]pyridazine, bases such as TMP2Zn center dot MgCl2 center dot 2 LiCl, in the presence or absence of BF3 center dot OEt2, led to regioselective metalations at positions 3 or 8. Subsequent functionalizations were achieved with TMPMgCl center dot LiCl, producing various polysubstituted derivatives (up to penta-substitution). X-ray analysis confirmed the regioselectivity for key functional heterocycles

Calculation-Driven Regioselective Functionalization of the Imidazo[1,2-a]pyrazine Scaffold via Zinc and Magnesium Organometallic Intermediates

Straightforward calculations such as determinations of pKa values and N-basicities have allowed the development of a set of organometallic reactions for the regioselective functionalization of the underexplored imidazo[1,2 a]pyrazine. Thus, regioselective metalations of 6 chloroimidazo[1,2-a]pyrazine using TMP-bases (TMP = 2,2,6,6-tetramethylpiperidyl) such as TMPMgCl∙LiCl and TMP2Zn∙2MgCl2∙2LiCl provided Zn- and Mg-intermediates, that after quenching with various electrophiles gave access to polyfunctionalized imidazopyrazine heterocycles. Additionally, the use of TMP2Zn∙2MgCl2∙2LiCl as base for the first metalation allowed an alternative regioselective metalation. Nucleophilic additions at position 8 as well as selective Negishi cross-couplings complete the set of methods for selectively decorating this heterocycle of the future