Remarkably pair- and regioselective carbon-carbon bond-forming reaction of zirconacyclopentane derivatives with Grignard reagents

Takahashi, Tamotsu; Seki, Takashi; Nitto, Yu; Saburi, Masahiko; Rousset, Christophe; Negishi, Ei‐ichi

doi:10.1021/ja00016a051

Cited by 173 publications

(43 citation statements)

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“…All of the steps proposed above have been independently and amply supported (Scheme 2). We believe that both the discovery of the Dzhemilev ethylmagnesiation and our mechanistic clarification 22 have not only clearly established the existence of both acyclic and cyclic carbozirconation processes but also alerted us to sharply and carefully distinguish some seemingly analogous carbometalation reactions of zirconocene derivatives. We were later further surprised by the existence of bimetallic (involving both Zr and Al) cyclic carbozirconation of alkynes and alkenes that may be viewed as a hybrid of acyclic and cyclic carbozirconation 23 (Scheme 3).…”

Section: Historical and Mechanistic Background Of Carbometalation Of mentioning

confidence: 80%

Discovery of ZACA reaction − Zr-catalyzed asymmetric carboalumination of alkenes

Negishi¹

2010

Arkivoc

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This paper is dedicated to Professor U. M. Dzhemilev in recognition and appreciation of his pioneering contributions to organometallic chemistry Abstract A single-stage, i.e., degree of polymerization of one, and enantioselective version of the ZieglerNatta alkene polymerization was envisioned as a potentially significant and useful method for catalytic asymmetric C-C bond formation, shortly after the corresponding alkyne version involving Zr-catalyzed alkylalumination of alkynes was discovered in 1978. However, the discovery of such an asymmetric reaction proved to be a major challenge. At least three widely observable unwanted side reactions, i.e., (1) cyclic carbometalation, (2) β-H transfer hydrometalation, and (3) alkene polymerization, represented by the Ziegler-Natta polymerization, were noted and were to be avoided. With Zr as the metal at the catalytic center, we eventually came up with a notion that di-or multiple alkylation of Zr was to be avoided for achieving superior acyclic asymmetric carbometalation. This, in turn, led us to avoid the use of highly nucleophilic alkylmetals containing alkali metals and Mg. Aluminum used in ZieglerNatta polymerization that can selectively monoalkylate Zr proved to be one of a very limited number of favorable metals. Even so, undesirable cyclic carbozirconation can occur in nonpolar solvents via intricate bimetallic routes to cyclic organozirconium species. The vastly different reactant-catalyst stoichiometry and the absence of polymerization promotors, such as methylaluminoxane, in our investigations permit us to ignore the Ziegler-Natta polymerization as a serious and unwanted side reaction, although use of limited amounts of promotors can in some cases accelerate otherwise sluggish ZACA reactions. Selection of the currently used Zr catalysts including (R)-and (S)-(NMI) 2 ZrCl 2 , dichlorobis(neomenthylindenyl)zirconium was made by screening 15 or so known chiral zirconocene derivatives. Systematic scientific design and screening of chiral ligands are clearly highly desirable, and efforts along this line are ongoing. Even at the current level of development, however, the ZACA reaction shows considerable promise as an efficient and selective method for catalytic asymmetric C-C bond formation, which has already been used to significantly modernize and improve syntheses of natural products including deoxypolypropionates and isoprenoids of biological and medicinal interest.

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Section: Historical and Mechanistic Background Of Carbometalation Of mentioning

confidence: 80%

Discovery of ZACA reaction − Zr-catalyzed asymmetric carboalumination of alkenes

Negishi¹

2010

Arkivoc

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“…However, in 1991 the reaction was unexpectedly shown to proceed by a multistep catalytic cycle involving b CÀH activation [28] (Scheme 5). Fortunately, each of the steps in the catalytic cycle was stoichiometrically observable, and the key to the [28] which was not clarified in independently reported other mechanistic suggestions. [29] Failure to achieve methylmagnesation is readily explained by the absence of a b CÀH bond in Me.…”

Section: Discussionmentioning

confidence: 99%

Principle of Activation of Electrophiles by Electrophiles through Dimeric Association—Two Are Better than One

Negishi

1999

Chem. Eur. J.

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Electron-deficient metal compounds can be significantly activated as electrophiles through dimeric (or polymeric) association with either the same or different electrophiles. Although this phenomenon has played an important role in many reactions, such as the Friedel ± Crafts reaction and the Ziegler ± Natta polymerization, it has apparently only recently been fully recognized. Its widespread exploitation promises to lead to many new synthetically useful reactions as well as ready and accurate interpretations of mechanistic and structural phenomena in acid-catalyzed and -promoted reactions.

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“…A later report (30) on a closely related reaction with ''cationic'' chiral zirconocene derivatives should be noted. Clearly, from the results presented above, the Zr-catalyzed carbometallation is multimechanistic (23,(31)(32)(33)(34)(35)(36) and sensitive to several critical factors including ligands (22), solvents (23), and metal countercations of alkylmetals. With respect to metal countercations, the following generalizations may be presented as useful guidelines (36).…”

Section: Design Of Protocolsmentioning

confidence: 99%

“…With respect to metal countercations, the following generalizations may be presented as useful guidelines (36). (i) Alkylmagnesium derivatives readily dialkylate dihalozirconium derivatives, leading to the formation of zirconacyclopropanes (or alkenezirconocenes) that can undergo cyclic carbozirconation (32). It should be noted here that others (37)(38)(39)(40) have developed mutually related Zr-catalyzed asymmetric COC bond-forming reactions that are thought to involve cyclic carbozirconation (32).…”

Section: Design Of Protocolsmentioning

confidence: 99%

An efficient and general route to reduced polypropionates via Zr-catalyzed asymmetric C—C bond formation

Negishi

Tan²,

Liang³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

104

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An efficient and general method for the synthesis of reduced polypropionates has been developed through the application of asymmetric carboalumination of alkenes catalyzed by dichlorobis(1-neomenthylindenyl)zirconium [(NMI) 2ZrCl2]. In this investigation, attention has been focused on those reduced polypropionates that are ␣-monoheterofunctional and either -ethyl or -n-propyl. The reaction of 3-buten-1-ol with triethylaluminum (Et 3 Al) or tripropylaluminum ( n Pr3Al) in the presence of (NMI)2ZrCl2 and isobutylaluminoxane gave, after protonolysis, (R)-3-methyl-1-pentanol as well as (R)-and (S)-3-methyl-1-hexanols in 88 -92% yield in 90 -92% enantiomeric excess in one step. These 3-monomethyl-1-alkanols were then converted to two stereoisomers each of 2,4-dimethyl-1-hexanols and 2,4-dimethyl-1-heptanols via methylalumination catalyzed by (NMI) 2ZrCl2 and methylaluminoxane followed by oxidation with O 2. The four-step (or three-isolation-step) protocol provided syn-2,4-dimethyl-1-alkanols of >98% stereoisomeric purity in Ϸ50% overall yields, whereas (2S,4R)-2,4-dimethyl-1-hexanol of comparable purity was obtained in 40% overall yield. Commercial availability of (S)-2-methyl-1-butanol as a relatively inexpensive material suggested its use in the synthesis of (2S,4S)-and (2R,4S)-2,4-dimethyl-1-hexanols via a three-step protocol consisting of (i) iodination, (ii) zincation followed by Pd-catalyzed vinylation, and (iii) Zr-catalyzed methylalumination followed by oxidation with O 2. This three-step protocol is iterative and applicable to the synthesis of reduced polypropionates containing three or more branching methyl groups, rendering this method for the synthesis of reduced polypropionates generally applicable. Its synthetic utility has been demonstrated by preparing the side chain of zaragozic acid A and the C11-C20 fragment of antibiotics TMC-151 A-F. O ligo-and poly(alkene)s with methyl groups bonded to alternating carbon atoms in the main chain (compound 1 in Fig. 1) are important structural units in both polymer materials chemistry (1) and natural products chemistry. The latter includes those reduced polypropionates that contain (i) two methylbranched asymmetric carbon centers, such as zaragozic acid A (compound 2 in Fig. 1) (2), and (ii) three methyl-branched asymmetric carbon centers, such as antibiotics TMC-151 A-F (compound 3 in Fig. 1) (3). The degree of polymerization of poly(propylene) usually exceeds 10 3 . As a consequence, most of the methyl-branched carbon centers may be considered to be ''virtually achiral,'' rendering their absolute configuration practically insignificant. On the other hand, their relative stereochemistry, termed tacticity, is of crucial importance in various respects. In the cases of reduced polypropionates, where the degree of polymerization is mostly Ͻ10, typically 2-4, both absolute and relative configurations of compound 1 (Fig. 1) are critically important. It is therefore essential to construct each methyl-bearing asymmetric carbon center with the correct absolute configurati...

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Remarkably pair- and regioselective carbon-carbon bond-forming reaction of zirconacyclopentane derivatives with Grignard reagents

Cited by 173 publications

References 0 publications

Discovery of ZACA reaction − Zr-catalyzed asymmetric carboalumination of alkenes

Discovery of ZACA reaction − Zr-catalyzed asymmetric carboalumination of alkenes

Principle of Activation of Electrophiles by Electrophiles through Dimeric Association—Two Are Better than One

An efficient and general route to reduced polypropionates via Zr-catalyzed asymmetric C—C bond formation

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