Tandem Inter [4 + 2]/Intra [3 + 2] Cycloadditions of Nitroalkenes. Asymmetric Synthesis of Highly Functionalized Aminocyclopentanes Using the Bridged Mode (β-Tether) Process

Denmark, Scott E.; Dixon, J. A.

doi:10.1021/jo9802170

Cited by 34 publications

(17 citation statements)

References 78 publications

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“…While the C 6 −C 7 double bond of DNBF behaves as the dienophile in the condensation leading to 6 , it is part of the O 6 −N 6 −C 6 −C 7 fragment, which acts as a heterodienic moiety in the condensation pathway leading to 7 . The formation of 6 and 7 highlights the ambident Diels−Alder reactivity of DNBF while adding to the evidence that nitrobenzofuroxans are 10π-electron heteroaromatics of low resonance energy. 1a,5d,e In this regard, the behavior of DNBF may be compared to that of nitroalkenes, which are known to react as dienophiles or heterodienes, depending upon the experimental conditions and the systems at hand. − In particular, Denmark and co-workers have recently reported the formation of a number of dihydrooxazine N -oxide structures from Lewis-acid promoted [4 + 2] cycloadditions of nitroalkenes with various dienophiles, including cyclopentadiene. , …”

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confidence: 99%

Competitive and Consecutive Inverse and Normal Electron Demand Cycloadditions in the Reaction of 4,6-Dinitrobenzofuroxan with Cyclopentadiene

et al. 1999

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mentioning

confidence: 99%

Competitive and Consecutive Inverse and Normal Electron Demand Cycloadditions in the Reaction of 4,6-Dinitrobenzofuroxan with Cyclopentadiene

et al. 1999

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“…In addition, we have observed that the reaction selectivity has also been dramatically affected [22] [31]. With SnCl 4 , the [4 2] reaction generally proceeds through a ul-type transition structure (exo with respect to the OR group in the vinyl ether).…”

Section: Discussion ± 41 [4 2] Cycloadditionmentioning

confidence: 99%

Tandem Inter [4+2]/Intra [3+2] Cycloadditions of Nitroalkenes. Application to the Synthesis of Aminocarbasugars

Denmark

Juhl

2002

HCA

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Dedicated to Professor Dieter Seebach on the happy occasion of his 65th birthday The tandem inter [4 2]/intra [3 2] cycloaddition of nitroalkenes in the bridged mode was applied to the stereoselective synthesis of b-d-4-amino-2,4-dideoxycarbagulose, a representative aminocarbasugar. The synthesis required only five steps from known materials and delivered the protected aminocarbasugar (À)-20 in excellent yield (see Scheme 9). The success of the synthetic sequence relies on 1) the ability to incorporate Osubstituents at the nitroalkene moiety, 2) the identification of a suitably modified chiral dienophile, and in particular 3) the development of specific experimental conditions and protocols that allow for the formation and isolation of the highly sensitive nitroso acetals. The reduction of the C(1) carbonyl group of ()-19 gave unexpected stereoselectivity, which could be rationalized by a conformational inversion of the substrate (see Scheme 11).

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“…Thus, lactam 8b was synthesized as reported, 1a with slight modification: The S-enantiomer of 1-(2,4,6-triisopropylphenyl)ethanol ( 5), chosen to gain access to the desired antipodal series, was converted in high yield to the dichloroenol ether 6, which in turn was treated with 2 equivalents of n-BuLi, followed by allyl iodide, to yield ynol ether 7a (Scheme 2). Partial reduction of the triple bond was performed with DIBAL-H in toluene at 50°C, 6 instead of by catalytic hydrogenation with the Lindlar catalyst, to give enol ether 7b, now free of the 10-20% of over-reduced material previously observed on hydrogenation. 1a Diastereoface-selective cycloaddition of dichloroketene to 7b, followed by Beckmann ring expansion and dechlorination, then afforded lactam 8b in 38% overall yield for the five steps (82%/step).…”

Section: Methodsmentioning

confidence: 99%

Extending the Scope of the [2+2] Cycloaddition of Dichloroketene to Chiral Enol Ethers: Synthesis of (-)-Detoxinine

Ceccon¹,

Poisson²,

Greene³

2005

Synlett

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Allylic oxidation of a known lactam, obtained by asymmetric [2+2] cycloaddition of dichloroketene to a chiral enol ether, followed by Beckmann ring expansion and dechlorination, affords a potential intermediate for the synthesis of various natural products. The usefulness of this intermediate is first demonstrated by an asymmetric synthesis of (-)-detoxinine.The [2+2] cycloaddition of dichloroketene to chiral enol ethers has already proven highly effective for the synthesis of several natural alkaloids, 1 including the simple azasugars (-)-2-epilentiginosine and (+)-lentiginosine. 1b To demonstrate that this chemistry can also provide access to the more complex indolizidine and pyrrolizidine azasugars, we have selected for synthesis (+)-castanospermine (1), (-)-swainsonine (2), and (+)-australine (3), popular synthetic targets that are potent inhibitors of glycosidases and of potential use in cancer chemotherapy ( Figure 1). 2 A common intermediate in our synthetic strategy appeared to offer also an approach to the unusual amino acid (-)-detoxinine (4), 3 the parent structure of the depsipeptide metabolites of the detoxin complex, which has been isolated from various strains of streptomyces and displays a unique detoxification effect in both plant and animal cells. 4 In this communication, we describe a non-chiral pool, stereoselective synthesis of (-)-detoxinine. Figure 1The pivotal intermediate in our program was anticipated to be allylic alcohol III (Scheme 1). Since a preparation of highly diastereomerically enriched lactam II from enantiopure 1-(2,4,6-triisopropylphenyl)ethanol was already available from previous work in our laboratory, 1a its allylic oxidation to access III seemed worth examining, particularly in view of the encouraging literature precedent with SeO 2 on related systems. 5 Scheme 1Thus, lactam 8b was synthesized as reported, 1a with slight modification: The S-enantiomer of 1-(2,4,6-triisopropylphenyl)ethanol (5), chosen to gain access to the desired antipodal series, was converted in high yield to the dichloroenol ether 6, which in turn was treated with 2 equivalents of n-BuLi, followed by allyl iodide, to yield ynol ether 7a (Scheme 2). Partial reduction of the triple bond was performed with DIBAL-H in toluene at 50°C, 6 instead of by catalytic hydrogenation with the Lindlar catalyst, to give enol ether 7b, now free of the 10-20% of over-reduced material previously observed on hydrogenation. 1a Diastereoface-selective cycloaddition of dichloroketene to 7b, followed by Beckmann ring expansion and dechlorination, then afforded lactam 8b in 38% overall yield for the five steps (82%/step). The diasteromeric purity of 8b was found, as previously, to be excellent (ca. 95%, 1 H NMR); furthermore, the minor diastereomers, conveniently, filtered out over the subsequent steps of the synthesis.It was found that allylic oxidation of 8b under Sharpless conditions (SeO 2 , t-BuOOH, ClCH 2 CH 2 Cl, reflux) did indeed lead to the formation of the desired product, but initially in only 35% yield. 8 Optimiz...

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Tandem Inter [4 + 2]/Intra [3 + 2] Cycloadditions of Nitroalkenes. Asymmetric Synthesis of Highly Functionalized Aminocyclopentanes Using the Bridged Mode (β-Tether) Process

Cited by 34 publications

References 78 publications

Competitive and Consecutive Inverse and Normal Electron Demand Cycloadditions in the Reaction of 4,6-Dinitrobenzofuroxan with Cyclopentadiene

Competitive and Consecutive Inverse and Normal Electron Demand Cycloadditions in the Reaction of 4,6-Dinitrobenzofuroxan with Cyclopentadiene

Tandem Inter [4+2]/Intra [3+2] Cycloadditions of Nitroalkenes. Application to the Synthesis of Aminocarbasugars

Extending the Scope of the [2+2] Cycloaddition of Dichloroketene to Chiral Enol Ethers: Synthesis of (-)-Detoxinine

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