Catalytic Asymmetric Allylic C−H Activation as a Surrogate of the Asymmetric Claisen Rearrangement

Davies, Huw M. L.; Ren, Pingda; Jin, Qihui

doi:10.1021/ol0167255

Cited by 88 publications

(70 citation statements)

References 21 publications

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“…The competing direct COH activation is usually a fairly significant side reaction. In general, the donor͞acceptor-substituted carbenoids do not cyclopropanate trisubstituted alkenes but there are some exceptions (14). For example, extension of the chemistry to siloxycyclopentene 18 as substrate was not successful because in this case, cyclopropane 19 was the dominant product rather than allylic COH functionalization products 20 and 21 (Eq.…”

Section: Methodsmentioning

confidence: 99%

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Catalytic asymmetric reactions for organic synthesis: The combined C—H activation/Cope rearrangement

Davies

Jin

2004

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

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The development of new catalytic asymmetric reactions can lead to exciting new strategies for organic synthesis. This article describes the synthetic utility of the combined COH activation͞Cope rearrangement, achieved by dirhodium tetraprolinate-catalyzed reaction of vinyldiazoacetates with compounds containing allylic COH bonds. The transformation is highly diastereoselective and enantioselective. The product distribution, however, is highly substrate dependent, the major side products being either direct COH activation or cyclopropanation.T he field of chiral catalysis has experienced explosive growth over the last two decades (1, 2). By now, many of the classic reactions of organic synthesis can be achieved in a highly asymmetric manner. One of the new frontiers for asymmetric catalysis is the discovery of new catalytic asymmetric methods that do not have an established achiral counterpart (3). For some time we have been exploring the chemistry of donor͞acceptor-substituted rhodium carbenoids (2) as a possible source of these new catalytic asymmetric transformations (Eq. 1) (4). Because of the presence of the donor group (typically vinyl or aryl), 2 are much more stabilized than the conventional carbenoids, which contain only electron acceptor groups (typically ester, keto, phosphonate, sulfonate, cyano or nitro) (5, 6). Consequently, 2 undergo a range of transformations with unprecedented regioselectivity and stereoselectivity (4).Our studies into the chemistry of donor͞acceptor-substituted carbenoids have already led to a number of exciting methods for catalytic asymmetric synthesis. The dirhodium tetraprolinate complex Rh 2 (S-DOSP) 4 [S-DOSP is S-(N-dodecylbenzenesulfonyl)prolinate; see Eq. 2] is an exceptional chiral catalyst for these carbenoids, resulting in generally high levels of asymmetric induction (7). These methods include cyclopropanation of alkenes (Eq. 2) (8), [3 ϩ 4] cycloaddition between vinylcarbenoids and dienes (Eq. 3) (9), [3 ϩ 2] cycloaddition between vinylcarbenoids and vinyl ethers (Eq. 4) (10), and intermolecular COH activation (Eq. 5) (11). A common feature of all of these transformations is the opportunity for the stereoselective generation of multiple stereocenters in a single step.Intermolecular COH activation is a very exciting reaction because it represents an additional strategic reaction for organic synthesis. Complementary carbenoid versions of many of the classic synthetic reactions of organic chemistry have been achieved. ␤-Hydroxy esters, usually derived from an aldol reaction, are stereoselectively formed by COH activation ␣ to oxygen (Eq. 6) (12).

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Section: Methodsmentioning

confidence: 99%

“…Allylic COH activation can lead to ␥,␦-unsaturated esters, the typical products of a Claisen rearrangement (Eq. 8) (14), or O-silylated 1,5-dicarbonyl compounds, the typical products of a Michael addition (Eq. 9) (15).…”

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confidence: 99%

Catalytic asymmetric reactions for organic synthesis: The combined C—H activation/Cope rearrangement

Davies

Jin

2004

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

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“…C-H functionalization can provide complementary approaches to achieve transformations equivalent to some of the classic reactions of organic synthesis [40][41][42][43][44][45] . For example, C-H functionalization adjacent to oxygen can lead to products that would be commonly derived from an aldol reaction (Fig.…”

Section: C-h Functionalization By Metal Carbenoidsmentioning

confidence: 99%

Catalytic C–H functionalization by metal carbenoid and nitrenoid insertion

Davies

Manning

2008

Nature

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Novel reactions that can selectively functionalize carbon-hydrogen bonds are of intense interest to the chemical community because they offer new strategic approaches for synthesis. A very promising 'carbon-hydrogen functionalization' method involves the insertion of metal carbenes and nitrenes into C-H bonds. This area has experienced considerable growth in the past decade, particularly in the area of enantioselective intermolecular reactions. Here we discuss several facets of these kinds of C-H functionalization reactions and provide a perspective on how this methodology has affected the synthesis of complex natural products and potential pharmaceutical agents.I n 2006, 31 new chemical entities were introduced to the world pharmaceutical market and 2,075 molecules were in phase I or II of clinical development 1 . The majority of these were smallmolecule (relative molecular mass ,1,000) organic compounds 2 . As knowledge about the specific interactions of drugs in vivo increases, often so does the structural complexity of new drug targets. A major obstacle to the development of such drugs is the difficulty associated with synthesizing large quantities in an economical fashion, because complex multi-step syntheses are usually required. In the general media, it is often overlooked that the accessibility of the components required for these new treatments will often govern their eventual success or failure. Likewise, a design element of any pharmaceutical agent is the expectation that the target compounds can be made economically. Therefore, new strategies for synthesis can become enabling technologies, making available new targets and materials that would have been previously out of range. For example, new methodologies such as metal-catalysed crosscoupling 3 and olefin metathesis 4-6 have rapidly become central transformations in the synthesis of new pharmaceutical agents. Selective C-H functionalization is a class of reactions that could lead to a paradigm shift in organic synthesis, relying on selective modification of ubiquitous C-H bonds of organic compounds instead of the standard approach of conducting transformations on pre-existing functional groups. The reactive sites in each type of transformation are very different, as illustrated in Fig. 1.The many opportunities associated with C-H functionalization has made this field an active area of research. Organometallic chemists have focused much attention on developing 'C-H activation' strategies, whereby a highly reactive metal complex inserts into a C-H bond, activating the system for subsequent transformations 7-9 . One of the major challenges associated with this chemistry has been to render it catalytic in the metal complex 10 . A partial solution to this problem has been to use neighbouring functionality to direct less reactive metal complexes to the site for functionalization. Numerous reviews have been written about this method for C-H functionalization [11][12][13][14][15][16][17] . Here, however, we highlight another approach, in which a divalent c...

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“…64,163,164 Improvements in both yields and enantioselectivity were noted upon changing from an electron-donating (X = OMe) to an electron-withdrawing (X = Cl) aromatic substituent for aryl diazoacetate precursors, 67,163,165,166 as had previously been noted in intramolecular C-H insertion studies. 93,107 As seen in Scheme 16, insertion is favoured at positions α to oxygen, 62,167,168 with the same preference also holding true for insertion adjacent to nitrogen, 63,65,124,164,169,170 and at benzylic 64,171 and allylic 20,[172][173][174] sites. The use of hydrocarbon solvents (hexane, 2,2-dimethylbutane) for intermolecular C-H insertion processes has also been found to increase asymmetric induction, compared with the use of polar solvents, 64,173,175 a trend also observed for asymmetric cyclopropanation reactions.…”

Section: Scheme 16mentioning

confidence: 79%

“…93,107 As seen in Scheme 16, insertion is favoured at positions α to oxygen, 62,167,168 with the same preference also holding true for insertion adjacent to nitrogen, 63,65,124,164,169,170 and at benzylic 64,171 and allylic 20,[172][173][174] sites. The use of hydrocarbon solvents (hexane, 2,2-dimethylbutane) for intermolecular C-H insertion processes has also been found to increase asymmetric induction, compared with the use of polar solvents, 64,173,175 a trend also observed for asymmetric cyclopropanation reactions. 60 Control of regiochemistry is also possible for intermolecular C-H insertion reactions of donor/acceptor carbenoids in the presence of Rh 2 (S-DOSP) 4 .…”

Section: Scheme 16mentioning

confidence: 79%