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

Zincation of 4,4-dimethyloxazoline using TMPZnCl·LiCl

Various functionalized aryl and heteroaryl aluminum reagents were obtained by performing I-Li or Br-Li exchange reactions with the corresponding unsaturated organic halides in the presence of i-Bu2AlCl. By means of an appropriate catalyst, the resulting new aluminum species were directly acylated, allylated or arylated. 1,4-Michael additions to enones have also been achieved

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

Iron‐Mediated Electrophilic Amination of Organozinc Halides using Organic Azides

A wide range of alkyl‐, aryl‐ and heteroarylzinc halides were aminated with highly functionalized alkyl, aryl, and heterocyclic azides. The reaction proceeds smoothly at 50 °C within 1 h in the presence of FeCl3 (0.5 equiv) to furnish the corresponding secondary amines in good yields. This method was extended to peptidic azides and provided the arylated substrates with full retention of configuration. To demonstrate the utility of this reaction, we prepared two amine derivatives of pharmaceutical relevance using this iron‐mediated electrophilic amination as the key step

A Predictive Model Towards Site‐Selective Metalations of Functionalized Heterocycles, Arenes, Olefins, and Alkanes using TMPZnCl⋅LiCl

The development of a predictive model towards site‐selective deprotometalation reactions using TMPZnCl⋅LiCl is reported (TMP=2,2,6,6‐tetramethylpiperidinyl). The pKa values of functionalized N‐, S‐, and O‐heterocycles, arenes, alkenes, or alkanes were calculated and compared to the experimental deprotonation sites. Large overlap (>80 %) between the calculated and empirical deprotonation sites was observed, showing that thermodynamic factors strongly govern the metalation regioselectivity. In the case of olefins, calculated frozen state energies of the deprotonated substrates allowed a more accurate prediction. Additionally, various new N‐heterocycles were analyzed and the metalation regioselectivities rationalized using the predictive model

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

Preparation of polyfunctional arylzinc organometallics in toluene by halogen/zinc exchange reactions

A wide range of polyfunctional diaryl-and diheteroarylzinc species were prepared in toluene within 10 min to 5 h through an I/Zn or Br/Zn exchange reaction using bimetallic reagents of the general formula R’2Zn·2LiOR (R’=sBu, tBu, pTol). Highly sensitive functional groups, such as a triazine, a ketone, an aldehyde, or a nitro group, were tolerated in these exchange reactions, enabling the synthesis of a plethora of functionalized (hetero)arenes after quenching with various electrophiles. Insight into the constitution and reactivity of these bimetallic mixtures revealed the formation of highly active lithium diorganodialkoxyzincates of type[R’2Zn-(OR)2Li2]

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