Recovery of Carbonyl Compounds from <i>N</i>,<i>N</i>-Dialkylhydrazones

Enders, Dieter; Wortmann, Lars; Peters, René

doi:10.1021/ar990062y

Cited by 136 publications

(75 citation statements)

References 72 publications

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“…The auxiliary itself is liberated in an altered form that hinders recycling. [4] Given these limitations, it is apparent that asymmetric a-alkylation of ketones remains an unsolved problem. Herein, we report a substantial advance in this field through the development of chiral N-amino cyclic carbamates (ACCs).…”

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confidence: 99%

Simple and Efficient Asymmetric α‐Alkylation and α,α‐Bisalkylation of Acyclic Ketones by Using Chiral N‐Amino Cyclic Carbamate Hydrazones

Lim

Coltart

2008

Angew Chem Int Ed

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Ketone a-alkylation is fundamental to organic synthesis. Remarkably, however, only one effective asymmetric version of this transformation applicable to acyclic systems is available. [1][2][3] Introduced over 25 years ago, this method is based on the alkylation of metalated SAMP/RAMP hydrazones, and has enabled numerous total syntheses.[1] Unfortunately, its further development has been impeded as a result of certain inherent limitations. For instance, the dialkyl hydrazones used are only weakly acidic, so azaenolate formation requires exposure to lithium diisopropylamide (LDA) for 2-10 h.[1a] Alkylation must then be conducted at an extremely low temperature (À110 to À78 8C),[1a] making large-scale applications impractical. Moreover, removal of the costly auxiliary under recommended [1a] conditions (ozonolysis or quaternization/hydrolysis) limits functional group compatibility. The auxiliary itself is liberated in an altered form that hinders recycling.[4] Given these limitations, it is apparent that asymmetric a-alkylation of ketones remains an unsolved problem. Herein, we report a substantial advance in this field through the development of chiral N-amino cyclic carbamates (ACCs). These auxiliaries significantly diminish the drawbacks associated with the use of chiral dialkyl hydrazines, yet still provide excellent stereoselectivity. In addition, the auxiliaries exhibit a unique directing effect that overrides the inherent selectivity of LDA, thus enabling the asymmetric a,a-bisalkylation of ketones, a previously unattainable transformation.Hydrazones possessing an electron withdrawing group (1, Scheme 1), which we term activated hydrazones, are readily formed from the corresponding substituted hydrazines (e.g., hydrazides, sulfonyl hydrazides, etc.) and ketones under mild conditions, and are rapidly hydrolyzed under similarly mild conditions, making them excellent candidates for auxiliarybased synthetic methods. We anticipated that the enhanced acidity of these activated hydrazones would enable rapid metalation over a range of temperatures. Moreover, the substantial electron density imparted to the electron withdrawing group in the derived azaenolates (2) should lead to tight metal cation binding, in a manner analogous to, for example, chelation of hydroxamate anions. In the context of asymmetric transformations, this could potentially bring high facial selectivity during alkylation, even at temperatures well above À110 to À78 8C, as required of SAMP/RAMP systems. Collectively, these factors suggested that chiral hydrazines substituted with a conjugated electron-withdrawing group could provide the basis of a simple method for asymmetric ketone a-alkylation.We focused our initial studies along these lines on the easily accessible ACCs.[5] Thus, 3 was prepared by amination of the corresponding oxazolidinone and was then condensed with 3-pentanone to give 8 (Table 1). This activated hydrazone 8 was readily deprotonated with LDA at À78 8C and allylated in excellent yield (90 %). The auxiliary was also easily remo...

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confidence: 99%

Simple and Efficient Asymmetric α‐Alkylation and α,α‐Bisalkylation of Acyclic Ketones by Using Chiral N‐Amino Cyclic Carbamate Hydrazones

Lim

Coltart

2008

Angew Chem Int Ed

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“…An X-ray structure analysis of the crystalline hydrazone 36 ( Figure 5) established its (1S,4R,5R,9S,2ЈS)-configuration, so all that remained to do was cleave the two hydrazones 35 and 36 to the corresponding ketol enantiomers 37 and 38. This, however, turned out to be more difficult than anticipated, as all the acidic or reductive methods attempted for the cleavage of hydrazones [21] led to decomposition. Fortunately, ozonolysis with reductive work-up employing thiourea went smoothly, and the (-)-(1R,4S,5S,9R)-configured 37 as well as the (+)-(1S,4R,5R,9S)-configured enantiomer 38 were isolated in 40 % and 34 % yield, respectively.…”

Section: Resultsmentioning

confidence: 99%

From Vetiver to Patchouli: Discovery of a NewHigh‐Impact Spirocyclic Patchouli Odorant

2005

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Keywords: Fragrances / Olfactory properties / Patchouli / Spiro compounds / Structure-activity relationshipsIn the course of synthetic work on new vetiver odorants, a new, potent patchouli odorant was discovered. Its structure was elucidated as 1-hydroxy-1,4,7,7,9-pentamethylspiro-[4.5]decan-2-one (15/16), and both diastereoisomers were synthesized from the previously reported 4,7,7,9-tetramethyl-1-methylenespiro[4.5]decan-2-one by epoxidation with mchloroperoxybenzoic acid, reduction with lithium aluminum hydride, and subsequent oxidation with pyridinium chlorochromate or Dess-Martin periodinane. The 1,4-unlike-isomer 15 was found to be the diastereoisomer with the most powerful odor, and its excellent odor threshold of 0.067 ng/L air triggered the synthesis of the derivatives 19, 22, 23, and 26 possessing a different methyl substitution pattern or ring size. Glycol cleavage in the oxidation step was circumvented

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“…B. Natriumperborat, Natriumpercarbonat, metallische Peroxide, organische Hydroperoxide, Percarbonsäuren), die eine naturgemäß schlechte Atomökonomie ergeben. [7][8][9][10] …”

Section: Einführungunclassified

Palladium‐ und Gold‐Palladium‐Katalysatoren für die Direktsynthese von Wasserstoffperoxid

Edwards

Hutchings

2008

Angewandte Chemie

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Recovery of Carbonyl Compounds from N,N-Dialkylhydrazones

Cited by 136 publications

References 72 publications

Simple and Efficient Asymmetric α‐Alkylation and α,α‐Bisalkylation of Acyclic Ketones by Using Chiral N‐Amino Cyclic Carbamate Hydrazones

Simple and Efficient Asymmetric α‐Alkylation and α,α‐Bisalkylation of Acyclic Ketones by Using Chiral N‐Amino Cyclic Carbamate Hydrazones

From Vetiver to Patchouli: Discovery of a NewHigh‐Impact Spirocyclic Patchouli Odorant

Palladium‐ und Gold‐Palladium‐Katalysatoren für die Direktsynthese von Wasserstoffperoxid

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