The chemistry of lithiated phosphine oxides: the stereoselective synthesis of alkene-4,5-diols

Boesen, Thomas; Feeder, Neil; Eastgate, Martin D.; Fox, David J.; Medlock, Jonathan; Tyzack, Charles R.; Warren, Stuart

doi:10.1039/b008500f

Cited by 5 publications

(5 citation statements)

References 13 publications

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“…Hydroxyketone 10 can be made by the opening of THF 5 with TBAF (Scheme 4). 25 Keto-phosphinate ester 11 can be selectively synthesised by extended treatment of THF 5 with caesium fluoride in tert-butanol. The different reaction conditions and reaction times in these last two processes show that while the removal of the silyl group and subsequent ring opening are fast reactions, the fluoride-catalysed phosphoryltransfer from carbon to oxygen (alcohol 10 to phosphinate 11) is relatively slow.…”

Section: Methodsmentioning

confidence: 99%

“…Epoxide formation can occur only from the free alcohols 14 and 17 so benzoyl ester cleavage is responsible for the loss of stereochemical integrity in the above reactions, and modification of the cyclopropanation reaction conditions is necessary to avoid the ester cleavage. The solution to the problem came unexpectedly during the synthesis of olefin-diols 25 from related starting materials. The treatment of bis-benzoate 22 with LDA at −78 • C produced on work-up the acyl transfer product 10 (Scheme 7).…”

Section: Methodsmentioning

confidence: 99%

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Asymmetric cyclopropane synthesis via phosphine oxide mediated cascade reactions

et al. 2005

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A silyloxy-THF has been converted into a cyclopropane containing three stereocentres as mixture of diastereoisomers. The mechanism of the reaction has been established and the source of stereochemical leakage proposed. An alternative stereospecific cascade reaction has been discovered.Cyclopropanes appear in a range of natural products and medicinally active molecules. 1 Their asymmetric synthesis has therefore been the subject of much research effort. In previous work we have shown that benzoyloxy phosphine oxides 1 can be lithiated with concomitant benzoyl migration to give ketones 2. In the presence of trimethylsilyl chloride the reaction intermediate is intercepted to give silyloxytetrahydrofurans 3. 22 These heterocycles have been transformed into cyclopropanes 4 via a phosphoryl-transfer ring-closing mechanism (Scheme 1). 23, 24 We have previously shown that single enantiomers of (benzoyloxy)benzyl-substituted THFs, such as 5 (Scheme 2), can be converted into alkene-diols, 25 and Scheme 1 Reagents and conditions: i, LDA, THF, −78 • C; ii, LDA, Me 3 SiCl, THF, −78 • C; iii, t BuOK, t BuOH.Scheme 2 Reagents and conditions: i, t BuOK, t BuOH; ii, NaBH 4 , MeOH. The X-ray crystal structure of racemic 8 is also shown.it was hoped that these compounds could also be converted stereoselectively into cyclopropanes.When treated with potassium tert-butoxide in tert-butanol, the conditions previously used to make cyclopropanes (Scheme 2), silyloxy-THF 25 5 did not yield a single stereoisomer of benzoyloxy-cyclopropane 6, but a mixture of two nonbenzoylated isomeric cyclopropanes 7 and 8. The two cyclopropanes were both shown to be trans-isomers by reduction of trans-1,2-bisbenzoyl-cyclopropane 26 9 (Scheme 2). Sodium borohydride is mild enough to effect only a mono-reduction of the bis-ketone, but with poor stereoselectivity, to give a mixture of the same cyclopropanes 7 and 8. Racemic compounds 7 and 8 were useful in the accurate calibration of chiral HPLC (Daicel Chiralpak AD column), establishing that the major diastereoisomer formed from THF 5 was as single enantiomer (7), but that the minor diastereoisomer had an enantiomeric excess of only 64% (8). We therefore assumed that the major diastereoisomer formed from THF 5 was the expected one, albeit in de-acylated form. This was confirmed by X-ray T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Asymmetric cyclopropane synthesis via phosphine oxide mediated cascade reactions

et al. 2005

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“…Phosphane oxide-mediated olefin synthesis, i.e., reaction of lithium derivatives of alkyl diphenylphosphane oxides with aldehydes to give β-hydroxyphosphane oxides followed by separation of the stereoisomers, and stereospecific elimination of Ph 2 PO Ϫ with a sodium or a lithium base (HornerϪWittig olefin synthesis [21,22] ) seemed to offer a way out of the difficulties experienced with the non-stereoselective formation of the trisubstituted olefins rac-7 and rac-10 during the Julia-type reactions described above. Our concept was to convert the unsaturated lactone rac-12 into a π-allylϪpalladium complex and to trap this intermediate with a nucleophilic precursor of the diphenylphosphane ox- ide substituent.…”

Section: Synthesis Of Diphenylphosphane Oxides Rac-13b and Rac14bmentioning

confidence: 99%

Studies on an Oxidative 1,4‐Addition to s‐trans‐1,3‐Dienes, a Key Reaction in a Strigol Total Synthesis

et al. 2003

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Keywords: Oxidation / Olefination / Palladium / StereochemistryOxidation of 4,6-heptadienoic acid systems with hydrogen peroxide in the presence of a catalytic amount of diphenyl diselenide leads to 5-(3-hydroxypropenyl)dihydrofuran-2-one systems with defined relative configuration at the 4 and 7 positions (carboxylic acid numbering). A system having a six-membered ring as part of the s-trans-diene system was an intermediate in a strigol total synthesis; a second system lacking the six-membered ring is the subject of the present publication. We accomplished a stereoselective synthesis of

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“…However, the presence of the C-5 TBDMS blocking group, susceptible to removal at a late stage, rendered this path incompatible at the present time. On the basis of these considerations, we decided to install a benzoate protecting group on the secondary alcohol because we were full of hope that this functionality could be removed and replaced during the oxetane ring formation conditions (NaH, THF) like precedence …”

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confidence: 99%

“…Compound (+)- 17 was treated with NaH in DMF at 40 °C and the reaction was monitored by TLC. 1 H NMR analysis of aliquots showed that the fastest reaction was the removal of the benzoate ester . After complete cyclization, excess TBDMSCl/imidazole were added to give (−)- 18 in 71% overall yield.…”

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Chemoenzymatic Taxanes Approach Using Both Enantiomers of the Same Building Block. 2. Taxol CD Ring Unit

Uttaro¹,

Audran²,

Monti³

2005

J. Org. Chem.

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[reaction: see text] The enantioselective synthesis of the Taxol CD ring unit has been achieved starting from an enantiopure building block, the enantiomer of those previously utilized in the synthesis of the A ring unit. The key features of the present synthesis are astute use of both enantiomers of the same building block and complete control in the construction of five consecutive chiral centers.

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The chemistry of lithiated phosphine oxides: the stereoselective synthesis of alkene-4,5-diols

Cited by 5 publications

References 13 publications

Asymmetric cyclopropane synthesis via phosphine oxide mediated cascade reactions

Asymmetric cyclopropane synthesis via phosphine oxide mediated cascade reactions

Studies on an Oxidative 1,4‐Addition to s‐trans‐1,3‐Dienes, a Key Reaction in a Strigol Total Synthesis

Chemoenzymatic Taxanes Approach Using Both Enantiomers of the Same Building Block. 2. Taxol CD Ring Unit

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