LiCl-Mediated Preparation of Highly Functionalized Benzylic Zinc Chlorides

Metzger, Albrecht; Schade, Matthias A.; Knöchel, Paul

doi:10.1021/ol7030697

Cited by 158 publications

(82 citation statements)

References 32 publications

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“…From the latter perspective, Si may be more promising despite its inherently low reactivity [212]. Only a few limited cases with other metals, such as Cu, Li, and Mg, were reported for this type of coupling [183,213,214]. …”

Section: 5-dienes and 15-enynes Via Pd-catalyzed Cross-couplings Wmentioning

confidence: 99%

Pd‐Catalyzed Cross‐Coupling with Organometals Containing Zn, Al, Zr, and so on – The Negishi Coupling and Its Recent Advances

Kamada

Kim

et al. 2013

Metal‐Catalyzed Cross‐Coupling Reactions and More

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The Pd-or Ni-catalyzed cross-coupling reactions of organometals containing Zn, Al, Zr, and B as well as related reactions of those containing Mg and several other metals collectively have emerged as arguably the most widely applicable organic skeleton construction method discovered and developed over the past several decades, allowing synthetic chemists to prepare practically all types of organic compounds. In this chapter, some of the seminal and critically important discoveries and early developments in the 1970s as well as their current scope are briefly discussed. Some of the notable discoveries and developments include (i) identification of superior properties of Pd as a critical element for crosscoupling relative to Ni, (ii) the broad scope of Pd-or Ni-catalyzed cross-coupling with respect to metal countercations including Zn, Al, Zr, B, and Mg, (iii) the hydrometallation-Pd-catalyzed cross-coupling sequential processes for selective syntheses of alkenes, dienes, oligoenes, and oligoenynes, (iv) double metal catalysis involving Pd or Ni and added metal compounds containing Zn, In, Li, and others, and (v) realization of high turnover numbers (TONs) (≥10 3 -10 9 ) through the use of chelating phosphines, such as bis-[2-(diphenylphosphino)phenyl] ether (DPEphos) and 1,1 -Bis(diphenylphosphino)ferrocene (dppf).The Zr-catalyzed alkyne carboalumination and the Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction) have provided efficient and selective routes to (E)-trisubstituted alkenylalanes and 2-substituted chiral alkylalanes, respectively. These reactions provide two additional examples of prototypical transition metal-catalyzed organometallic reactions. Significantly, they can be readily combined with the Pd-or Ni-catalyzed cross-coupling for the synthesis of trisubstituted alkenes embracing a wide variety of natural products, such as terpenoids, carotenoids, and others, as well as various chiral organics including deoxypolypropionates and saturated terpenoids. The Zr-catalyzed alkyne carboalumination has been applied to the synthesis of a large number (>100) of natural products, while the ZACA reaction has been transformed from a mere scientific novelty to a full-fledged asymmetric synthetic method that is catalytic in both transition metal (Zr) and chiral auxiliaries through a series of breakthroughs.

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Section: 5-dienes and 15-enynes Via Pd-catalyzed Cross-couplings Wmentioning

confidence: 99%

Pd‐Catalyzed Cross‐Coupling with Organometals Containing Zn, Al, Zr, and so on – The Negishi Coupling and Its Recent Advances

Kamada

Kim

et al. 2013

Metal‐Catalyzed Cross‐Coupling Reactions and More

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“…This method has been extended to the preparation of benzylic zinc reagents [13]. A remarkable chemoselectivity is observed and functional groups, such as an acetyl group, are perfectly compatible with such synthesis.…”

Section: Reviewmentioning

confidence: 99%

“…Its half-life at 25 °C is approximately two days. The copper(I)-mediated acylation of 26 provides the expected diketone 27 in 74% yield (Scheme 5) [13–14]. …”

Section: Reviewmentioning

confidence: 99%

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

Knöchel¹,

Schade²,

Bernhardt³

et al. 2011

Beilstein J. Org. Chem.

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SummaryIn this review we summarize the most important procedures for the preparation of functionalized organzinc and organomagnesium reagents. In addition, new methods for the preparation of polyfunctional aryl- and heteroaryl zinc- and magnesium compounds, as well as new Pd-catalyzed cross-coupling reactions, are reported herein. Experimental details are given for the most important reactions in the Supporting Information File 1 of this article.

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“…[2] However, sensitive functional groups, such as aldehyde or ketone functionalities with a acidic hydrogen atoms, are only tolerated in special cases. [3] Furthermore, the reactivity of unsaturated zinc reagents toward acidic hydrogen atoms of alcohols and phenols precludes the performance of Negishi cross-coupling reactions [4] of aromatic iodides containing these functionalities. In contrast to organozinc reagents, organoindium reagents have been shown to be compatible with water and several important functionalities.…”

Section: Yi-hung Chen and Paul Knochel* Dedicated To Professor Rolf Hmentioning

confidence: 99%

Preparation of Aryl and Heteroaryl Indium(III) Reagents by the Direct Insertion of Indium in the Presence of LiCl

2008

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Functionalized organometallic compounds are key intermediates in organic synthesis. [1] In particular, organozinc reagents are compatible with a wide range of functional groups and have broad application in synthesis.[2] However, sensitive functional groups, such as aldehyde or ketone functionalities with a acidic hydrogen atoms, are only tolerated in special cases.[3] Furthermore, the reactivity of unsaturated zinc reagents toward acidic hydrogen atoms of alcohols and phenols precludes the performance of Negishi cross-coupling reactions [4] of aromatic iodides containing these functionalities. In contrast to organozinc reagents, organoindium reagents have been shown to be compatible with water and several important functionalities.[5] However, in classical syntheses of these organoindium compounds through Li/In or Mg/In transmetalation, the corresponding organometallic precursors require protecting groups. Recently, we reported that LiCl accelerates dramatically the insertion of zinc [6] or magnesium [7] into organic halides. Herein, we report a preparation of polyfunctional aryl and heteroaryl indium(III) reagents 1 through the direct insertion of indium metal in the presence of LiCl into iodides 2. To the best of our knowledge, only allyl, propargyl, [5] pentafluorophenyl, [8] and benzyl indium(III) reagents [9] have been prepared by the direct treatment of the corresponding halides with indium metal. Commercially available indium does not react with aryl iodides. However, when LiCl (2-4 equiv) [10] was added to indium powder (2-4 equiv) that had been activated with 1,2-dibromoethane and TMSCl [11] in THF, an efficient insertion occurred within 20 min to 24 h at 30-50 8C to provide polyfunctional aryl and heteroaryl indium(III) species 1 in 70-97 % yield (Scheme 1).Thus, the treatment of 4-iodoacetophenone (2 a) with activated indium powder (4 equiv) in the presence of LiCl (4 equiv) in THF at 50 8C for 24 h provided the desired aryl indium(III) reagent 1 a in 96 % yield, as indicated by iodolysis (Table 1). [12] No insertion occurred in the absence of LiCl.Similarly, the iodoketones 2 b and 2 c were converted into the corresponding keto-substituted indium derivatives 1 b (50 8C, 24 h) and 1 c (35 8C, 2 h) in 93 and 90 % yield, respectively. The functionalized aryl iodides 2 d-g with an ester or aldehyde functionality also reacted smoothly with indium metal in the presence of LiCl to give the organoindium(III) reagents 1 d-g in 70-86 % yield. The presence of an electronwithdrawing group or metalation-directing group increased the insertion rate considerably. This method was extended to the preparation of heteroaryl indium(III) reagents. Heterocyclic iodides (and a heterocyclic bromide), some of which contained a ketone, aldehyde, or ester functionality, reacted smoothly with indium powder in the presence of LiCl to furnish the heteroaryl indium(III) compounds 1 h-m in 78-97 % yield (Table 1, entries 8-13). This method provides access to organoindium reagents containing a range of important and sensitive funct...

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LiCl-Mediated Preparation of Highly Functionalized Benzylic Zinc Chlorides

Cited by 158 publications

References 32 publications

Pd‐Catalyzed Cross‐Coupling with Organometals Containing Zn, Al, Zr, and so on – The Negishi Coupling and Its Recent Advances

Pd‐Catalyzed Cross‐Coupling with Organometals Containing Zn, Al, Zr, and so on – The Negishi Coupling and Its Recent Advances

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

Preparation of Aryl and Heteroaryl Indium(III) Reagents by the Direct Insertion of Indium in the Presence of LiCl

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