Organomagnesium reagents occupy a central position in synthetic organic and organometallic chemistry. Recently, the halogen-magnesium exchange has considerably extended the range of functionalized Grignard reagents available for synthetic purposes. Functional groups such as esters, nitriles, iodides, imines, or even nitro groups can be present in a wide range of aromatic and heterocyclic organomagnesium reagents. Also various highly functionalized alkenyl magnesium species can be prepared. These recent developments as well as new applications of organomagnesium reagents in cross-coupling reactions and amination reactions will be covered in this Review.
Magnesiumverbindungen spielen eine zentrale Rolle in der präparativen organischen und metallorganischen Chemie. Seit kurzem ermöglicht der Halogen‐Magnesium‐Austausch den Zugang zu einer Reihe funktionalisierter Grignard‐Reagentien. Ester‐, Nitril‐, Iod‐ und Iminfunktionen und sogar Nitrogruppen können in einer breiten Reihe aromatischer und heterocyclischer Organomagnesiumverbindungen vorhanden sein. Auch hoch funktionalisierte Alkenylmagnesiumspezies können auf diese Weise generiert werden. Diese neuen Entwicklungen sowie die Anwendung von Organomagnesiumreagentien in Kreuzkupplungen und Aminierungsreaktionen werden in diesem Aufsatz eingehend beschrieben.
Sensitive functional groups are tolerated in an iodine–zinc exchange reaction catalyzed by Li(acac). Aryl and heteroaryl diorganozinc compounds with keto, aldehyde, or isothiocyanate substituents can be prepared by this method (see example in scheme; acac=acetylacetone, NMP=1‐methyl‐2‐pyrrolidinone). Such zinc reagents serve as substrates for a wide variety of coupling reactions.
The asymmetric preparation of tertiary alcohols and amines is an important synthetic problem that has been the subject of numerous studies. [1, 2] Copper-catalyzed S N 2' substitutions are an excellent method for setting up chiral centers in cyclic and acyclic systems. [3][4][5] Only a few of these reactions can be applied to the construction of quaternary carbon centers. [6] We have recently reported an efficient anti-S N 2' allylic substitution reaction with pentafluorobenzoates of trisubstituted allylic alcohols that produces quaternary centers with almost complete transfer of the chiral information.[7] Herein, we report applications of this method for preparing chiral tertiary alcohols 1 and amines and isocyanates such as 2 and 3, which bear a tertiary chiral center, with high enantioselectivity starting from the chiral allylic substitution products 4, which were obtained from the allylic pentafluorobenzoates 5 (Scheme 1).In a typical procedure the E pentafluorobenzoate 5 a (97 % ee, entry 1 of Table 1) was treated with Pent 2 Zn (2 equiv) and CuCN·2 LiCl (1 equiv) in THF at À30 to À10 8C for 14 h to afford the expected anti-S N 2' substitution product 4 a (70 %, 96 % ee) with an almost perfect transfer of chiral information. Functionalized diorganozinc reagents such as (EtO 2 C(CH 2 ) 3 ) 2 Zn [8] reacted in a similar way providing the corresponding chiral esters 4 b (68 %, 96 % ee) and 4 c (58 %, 96 % ee) with the same level of enantioselectivity. In all these substitutions, allylic pentafluorobenzoates were used as substrates. Other allylic alcohol derivatives such as 2,6-difluorobenzoate 5 c (99 % ee) underwent the allylic substitution with optimum enantioselectivity leading to the E alkene 4 d in 85 % yield and 98 % ee (entry 4). These substrates also gave excellent results with purely alkyl-substituted allylic reagents such as 5 d (99 % ee, entry 5). In this case, the substitution with Et 2 Zn provided the E alkene 4 e (80 %, 96 % ee) bearing a quaternary center with three different alkyl substituents. Although allylic acetates react only sluggishly with diorganozinc reagents, in the case of the allylic acetate 5 e (97 % ee), which bears small substituents (Me and Et) at the double bond, an efficient substitution with Pent 2 Zn took place providing the E alkene 4 f in 60 % yield and 95 % ee.This substitution reaction proceeded with a reliable transfer of chirality (entries 7 and 8) and was also performed with secondary diorganozinc reagents like iPr 2 Zn to furnish the sterically hindered alkene 4 i (73 %, 95 % ee; entry 9). Interestingly, functionalized allylic pentafluorobenzoates such as 5 i (99 % ee) and 5 j (99 % ee) provided useful chiral building blocks like 4 j (69 %), 4 k (90 %), and 4 l (80 %) in enantiomerically pure form (99 % ee; entries 10-12).With the chiral alkenes of type 4 in hand, we then developed a straightforward oxidation sequence for the conversion of chiral alkenes 4 to either the corresponding aldehydes 12 or carboxylic acids 13 (Scheme 2). The former intermediate undergoes st...
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