A facile one-pot cyanation of primary and secondary alcohols. Application of some new Mitsunobu reagents

Tsunoda, Tetsuto; Uemoto, Kaori; Nagino, Chisato; Kawamura, Megumi; Kaku, Hiroto; Itô, Shô

doi:10.1016/s0040-4039(99)01509-9

Cited by 48 publications

(28 citation statements)

References 15 publications

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“…At this stage we used a Mitsunobu reaction for C-1 elongation to the cyanide alternative to tosylation and S N 2 displacement with sodium cyanide. [14] Reduction of nitrile 26 with DIBALH led to aldehyde 27 and subsequent Brown allylation [10] gave us alcohol 9 in very good yield and a high d.r. of 16:1.…”

Section: Resultsmentioning

confidence: 99%

The Laulimalide Family: Total Synthesis and Biological Evaluation of Neolaulimalide, Isolaulimalide, Laulimalide and a Nonnatural Analogue

Gollner

Altmann

Gertsch

et al. 2009

Chemistry A European J

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We herein describe in full detail the first total synthesis of the antitumor agents neolaulimalide and isolaulimalide as well as a highly efficient route to laulimalide. A Kulinkovich reaction followed by a cyclopropyl-allyl rearrangement is used to install the exo-methylene group. The C(2)-C(16) aldehyde fragment is coupled with the C(17)-C(28) sulfone fragments by a highly (E)-selective Julia-Lythgoe-Kocienski olefination to deliver the key intermediates of all three syntheses. Various conditions for the Yamaguchi macrolactonization are applied to close the individual macrocycles. Finally a carefully elaborated endgame was developed to solve the problem of acyl migration in the case of neolaulimalide. All compounds were tested against several cell lines. The cytotoxicity of neolaulimalide could be confirmed for the first time since its original isolation and it could be shown that it induces tubulin polymerization as efficiently as laulimalide.

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Section: Resultsmentioning

confidence: 99%

The Laulimalide Family: Total Synthesis and Biological Evaluation of Neolaulimalide, Isolaulimalide, Laulimalide and a Nonnatural Analogue

Gollner

Altmann

Gertsch

et al. 2009

Chemistry A European J

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“…[55,58] Applications of (cyanomethylene)trialkyl-or triphenylphosphoranes (12, Figure 7), spearheaded by Itô and Tsunoda, have extended CϪC bond formation reactions. [4e,41,42,59,60] With the use of cyanomethylenetrimethylphosphorane 12 (R ϭ Me) primary and secondary alcohols can be transformed into nitriles with acetone cyanohydrin, [41] primary alcohols can be converted into amines [61] or into one-carbon-atom extended nitriles, [62] and primary, secondary, and tertiary alcohols can be used for alkylation of 1H-indole and 9H-carbazole derivatives. [63] The phosphorane reagents are generally less active at room temperature.…”

Section: Alternative Reagentsmentioning

confidence: 99%

“…The products available via the Mitsunobu reaction have been expanded or the procedure has been improved to include styrene oxides with a high level of stereoretention, [32] oxetanes, [29] lactones from hindered chiral alcohols with retention of configuration, [73] aldehydes from 1,1-disubstituted-1,2-diols, [85] carbamate esters, [57,86,87] γ-lactams from amino alcohols, [88] primary amines, [89] tertiary benzylamines, [40] alkylated hydrazines, [90] nitriles, [41,61] isocyanates, [31] thiocyanates, [91] hydroxyalkyl azides, [69,92] and cisor trans-1,2-diazides from epoxides or trans-diols. [93] Hydra- zine derivatives can be obtained directly from the azodicarboxylate and an alcohol, [94] vinylhydrazinecarboxylates from ketones in the presence of dimethyl azodicarboxylate, [95] and hydrazylmethyl uracil derivatives from N 3 -benzyluracil, TMAD, and N-hydroxymethylphthalimide.…”

Section: Product Expansionmentioning

confidence: 99%

Recent Advances in the Mitsunobu Reaction: Modified Reagents and the Quest for Chromatography‐Free Separation

Dembiński

2004

Eur J Org Chem

179

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“…Thus, the very high reactivity observed for the bond formation of C-N, C-C, and others 12,13) renders these reagents and these procedures highly valuable and competitive from a synthetic point of view. Furthermore, it is a new substantial finding that the reagents can behave not only as a Wittig reagent 14) but also as a Mitsunobu-type reagent.…”

mentioning

confidence: 99%

Preparation of (Cyanomethylene)trimethylphosphorane as a New Mitsunobu-Type Reagent.

Izumi

Kaku

Tsunoda

2003

CHEMICAL & PHARMACEUTICAL BULLETIN

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The Mitsunobu reaction is a very versatile method for the alkylation of various nucleophiles (HA) with alcohols (ROH) to give RA, utilizing the redox system of diethyl azodicarboxylate (DEAD)-triphenylphosphine (TPP) (Fig. 1). 1,2) Without any prerequisite activation of the alcohol, it is a unique alkylation reaction and widely applied to various phases of organic synthesis. However, the reaction has a serious limitation; the acidic hydrogen in HA has to have pK a lower than 11 for the reaction to proceed satisfactorily. If HA has a pK a higher than 11, the yield of RA is considerably lower, and with HA having a pK a higher than 13, the desired reaction does not occur. In order to overcome these drawbacks and expand the versatility of the original Mitsunobu reaction, stabilized trialkylphosphoranes such as (cyanomethylene)tributylphosphorane (CMBP) 3) and (cyano-methylene)trimethylphosphorane (CMMP) 4) have been developed to replace the DEAD-TPP system.These new reagents were designed based on the structural similarity between the ylide 2 and the betaine 1 generated as an important intermediate in the Mitsunobu reaction (Fig. 2). The ylide 2, which is another resonance form of trialkylphosphorane, was expected to behave similarly with 1 towards a mixture of ROH and HA to yield RA along with the by-products, trialkylphosphine oxide and acetonitrile (Fig. 3).In fact, the trialkylphosphoranes, especially CMMP, mediate the Mitsunobu-type reactions of various kind of nucleophiles (Fig. 4) with pK a of 11-23, such as N-methyltosylamide (3, pK a 11.7), 5,6) (cyanomethyl)phenylsulfone (4, pK a 12.0 in DMSO 7) ), 5,6) (methylthiomethyl)tolylsulfone (5, pK a 23.4 in DMSO 8) ), 5,6) benzyl phenyl sulfone (6a, pK a 23.4 in DMSO 9) ), 10) 3-[(phenylsulfonyl)methyl]pyridine (6b, pK a 16.7 in DMSO 9) ) 10) and geranyl phenyl sulfone (7, pK a 22.5 in DMSO 9) ).11)The useful attributes of the new Mitsunobu reaction are as follows. 1) These reactions with secondary alcohols proceed with the complete Walden inversion of the stereochemistry at the carbinyl carbon.2) The reaction of the DEAD-TPP redox system (the traditional Mitsunobu reaction) is not normally effective at higher temperature, whereas the reaction of CMBP and CMMP even at higher temperature can be carried out satisfactorily, because they are quite thermally stable although very sensitive to air and moisture. Furthermore, 3) in the traditional Mitsunobu reaction, one problem is the laborious purification of the product from dihydro-DEAD and triphenylphosphine oxide, whereas the use of the phosphoranes leads to an easy workup. Acetonitrile produced in place of dihydro-DEAD can be easily evaporated, and the removal of tributyl-or trimethylphosphine oxide can be attained by SiO 2 column chromatography because of its high polarity. As an alternative workup for the reaction with CMMP, aqueous treatment of the reaction mixture is also quite effective because of the good aqueous solubility of trimethylphosphine oxide.Thus, the very high reactivity observed for the bond for...

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A facile one-pot cyanation of primary and secondary alcohols. Application of some new Mitsunobu reagents

Cited by 48 publications

References 15 publications

The Laulimalide Family: Total Synthesis and Biological Evaluation of Neolaulimalide, Isolaulimalide, Laulimalide and a Nonnatural Analogue

The Laulimalide Family: Total Synthesis and Biological Evaluation of Neolaulimalide, Isolaulimalide, Laulimalide and a Nonnatural Analogue

Recent Advances in the Mitsunobu Reaction: Modified Reagents and the Quest for Chromatography‐Free Separation

Preparation of (Cyanomethylene)trimethylphosphorane as a New Mitsunobu-Type Reagent.

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