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benzylchloride1
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Total Synthesis of Carpanone from Catechol
I am currently working on the total synthesis of carpanone starting from catechol. Carpanone is a molecule that is composed of 6 rings with 5
stereocenters. The proposed synthesis starts from catechol which is methyleneated with dichloromethane in dimethyl sulfoxide to form
1,2-methylenedioxybenzene. The 1,2-methylenedioxybenzene is then nitrated in acetic acid with nitric acid and acetic anhydride to form
4-nitro-1,2-methylenedioxybenzene which is then reduced to form 4-amino-1,2-methylenedioxybenzene.
The resulting aniline will then be diazotized and hydrolyzed to form 4-hydroxy-1,2-methylenedioxybenzene, or sesamol. This will then be
subjected to a Williamson ether synthesis with allyl bromide, The resulting allyl ether will then be treated with potassium hydroxide in
dimethylsulfoxide to form 2-(trans-1-propenyl)-4,5-methylenedioxyphenol. This will then be subjected to a copper catalyzed phenolic cross coupling
reaction which completes the total synthesis. This will be an interesting synthesis of a complex natural product which can readily be conducted in an
amateur setting.
References: Fieser, Williamson; Organic Experiments, 3rd edition. The catechol methylenation can be found on the internet easily, Rhodium.
Experimental:
Step 1. Formation of 1,2-methylenedioxybenzene
27.5g of catechol, 50 ml dimethylsulfoxide, and 30 ml of 50% sodium hydroxide was placed in a 500ml flask. The catechol dissolved to form a very dark
colored, viscous solution. This solution was heated at 98 Celsius for 30 minutes. Meanwhile, a solution of 30ml dichloromethane in 75 ml of
dimethylsulfoxide was prepared in a 1000ml flask equipped with an mechanical stirrer and reflux condenser. The solution of bis sodiium catechol
phenoxide was added rapidly to the DCM-DMSO solution. The solution was not added in portions because the solution would freeze slightly below 98C,
clogging the addition funnel. About 25% of the solution was lost in this manner. The solution was then refluxed for 2 hours and steam distilled to
recover the product. The steam distillate was extracted with 2-25ml portions of dichloromethane and the extracts were dried over magnesium sulfate,
filtered and the solvent removed with a rotary evaporator leaving an water white oil with a characteristic odor. 14.5g of 1,2-methylenedioxybenzene
was obtained, for a percentage yield of 47%. An infrared specrum indicated that no catechol was present due to the absence of hydroxyl absorbtions
around 3500cm^-1.2 strong absorbtion bands centered around 1230 and 1045 cm6-1 indicate the presence of an ether. An absorbance around 1380cm^-1
indicates alkyl carbon due to the methylenedioxy group. This indicates that the first step in the synthesis was attempted.
Step 2. Nitration of 1,2-methylenedioxybenzene
After an unsucceful nitration of 1,2-methylenedioxybenzene using a acetic, sulfuric, nitric acid mix similar to the method used to nitrate
acetanilide, another method was tried.
2.0g methylenedioxybenzene was dissolved in 10 ml glacial acetic acid in a 100 ml flask, a stirr bar was added and the mixture was chilled in an ice
bath. 3.0ml of 70% nitric acid was added in small portions, truning the solution yellow. 3.0ml of acetic anhydride prepared from sodium acetate and
disulfur dichloride was added. Immediately, a yellow precipitate of the nitro compound formed. The mixture was stirred for a hour in the ice bath. 50
ml of cold water was added with swirling, and the mixture was filtered. The yello colored nitro compound was then washed with 100ml of cold water and
allowed to dry over night. I still need to recrystallize the product.
This file contains a sketic of the proposed synthetic route
[ Attachment: Carpanone Synthesis.skc (10kB)
This file has been downloaded 1211 times
[Edited on 10-11-2009 by benzylchloride1]
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Nicodem
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What is the reference for that synthetic route you depicted in the attachment? BTW, please use pictures instead.
As it is shown, it does not make much sense. Phenolic couplings requires phenols while you show an oxidation of a phenyl vinyl ether instead. All the
total syntheses of carpanone that I could find use 6-propenyl-sesamol for the phenolic coupling/Diels-Alder tandem reaction. The 6-propenyl-sesamol
is prepared by the base catalysed double bond isomerisation of 6-allyl-sesamol which itself is prepared via the Claisen rearrangement of
O-allyl-sesamol.
Are you sure you did not misinterpreted your source?
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benzylchloride1
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The reference for the synthesis of carpanone is Organic experiments by Fieser, Williamson, this book has a procedure for the complete synthesis of the
desired product for students. My mistake, I forgot to draw the Clasien rearrangement leading to the ally phenol derivative, I will change the ISIS
draw image when I have a chance.
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mr.crow
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There are also many patents concerning benzodioxole methyleneation that may avoid the problems in the first step.
I haven't heard of the Claisen rearrangement being done in DMSO before. Ethanol is also a good solvent, I am not sure is base has any effect in this
case.
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Nicodem
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As long it is just a mistake, it does not really matter. I just found it impossible and was wandering what is all that about.
Why is the addition order reversed in the methylenation of catechole? Is there a particular reason? It only appears to have caused you troubles.
Nitration of 1,3-benzodioxole should work without acetanhydride. I do not understand why you could not get it nitrated with HNO3/H2SO4 in acetic acid,
because several literature examples use such conditions. Check J. Het. Chem., 28, 625-634 (10.1002/jhet.5570280316) for a detailed study
(yield was quantitative). At page 8 of patent US4554280 you have an example yielding 90% using just 65% HNO3 in acetic acid left stirring overnight.
What are you going to use for the reduction of the nitro compound? I would recommend you to use something simple, like hydrogenation over Pd-C which
can be done at 1atm, or reduction with sodium dithionite. Most metal-acid reduction systems are difficult to work up and some give lots of azo dyes
with electron rich nitroaromatics instead of cleanly reducing them to the amino product.
| Quote: | | I haven't heard of the Claisen rearrangement being done in DMSO before. Ethanol is also a good solvent, I am not sure is base has any effect in this
case. |
I think Benzylchloride1 made a mistake with that as well. The whole step of Claisen rearrangement and the subsequent step of double bond isomerisation
is missing. DMSO is probably used for the isomerisation, and not for the Claisen. The Claisen rearrangement is most commonly done solventless as long
as good care is taken in controlling the internal temperature (by keeping it bellow 250°C). Otherwise, clumsy chemists use reflux in
N,N-dimethylaniline (an effective and easy to wash off solvent). Ethanol can not be used, unless in a closed vessel, for the obvious reason of its low
boiling point.
[Edited on 10/11/2009 by Nicodem]
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DJF90
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1,2-dichlorobenzene is supposedly an effective solvent for aromatic claisen rearrangements. Not sure about ease of work up though. DMSO is high
boiling so that might relate to the use of it as a solvent in this step, and it likely stabilises the transition state also. Ethanol cannot be used
for a claisen rearrangement, it boils at a temperature far too low of whats needed.
The methylenation step would likely be higher yeilding using diiodomethane, obtainable via a finkelstein reaction on dichloromethane among other
methods. The use of alkali carbonate or hydride as base for forming the di-phenoxide would be advantageous also, preventing loss of diiodomethane to
Sn2 with hydroxide. DMSO should be fine as a solvent for the reaction, although you might consider using an alternative with lower boiling point to
aid ease of removal.
Using carbonate or hydride as the base, the reaction should be one pot. Why you added the phenoxide solution to the DMSO-DCM is beyond me, reverse
addition would have been far more applicable/advantageous.
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mr.crow
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Ethanol/water speeds up the Claisen reaction so it works at reflux temperatures. DMSO should work either way since its also polar.
You need a really strong polar aprotic solvent for the methyleneation because of the lower reactivity. DMSO and n-methyl pyrrolidone seem to be the
best, and sometimes a catalyst like CuO is used (according to various patents)
I think adding the phenoxide to the CH2Cl2 is done so there is always an excess of CH2Cl2 to prevent byproducts from forming (two catechols being
coupled together). There are of course different ways of doing it.
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DJF90
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Ethanol/water speeds up the claisen rearrangement? How so? I dont think I've ever seen a claisen run below 100C, of which your ethanol/water mix will
certainly boil below... and if such a reaction would work, I would suspect it would likely take a week or longer!
| Quote: |
You need a really strong polar aprotic solvent for the methyleneation because of the lower reactivity.
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Lower reactivity of what? The di-phenoxide or the dihalomethane (or di-chloro vs. di-iodo?)? Try and specify. Any solvent that promotes Sn2 reaction
should be applicable - chloride is a crappy leaving group hence the suggestion to use the di-iodomethane instead.
As to your suggestion of adding the di-phenoxide to the DCM is done so excess DCM is present to prevent the formation of bis-methylene bridged
catechols, there are two counter-arguments to this.
The first is that the solution of DCM-DMSO should be added rapidly - the Sn2 reaction (with DCM in particular, cf di-iodomethane) should be slower
than the rate of mixing, allowing DCM to be present in excess before the reaction "starts".
The second is that, once one halide has been displaced, the halomethylene group is bound to the now mono-phenoxide, and thus intramolecular
cyclisation (5-exo-trig) is far more entropically (and kinetically) favourable than the approach of another dihalomethane molecule to your phenoxide
and subsequent attack, unless of course you use the dihalomethane as your reaction solvent.
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mr.crow
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Here is a google book talking about the solvent effects
http://books.google.ca/books?id=55IGjy3CiAUC&lpg=PT16&am...
Wonder why they list ethanol/water if its at 170 degrees, doesn't make sense. The reaction is exothermic so you wouldn't want to speed it up 100 times
anyways.
Now for methyleneation the dichloride is very unreactive but more desirable then using di-iodo
Here is a paper, I can't remember where I found it. http://rapidshare.com/files/305281382/methylation_of_catecho... (will be deleted after 10 downloads or 90 days  )
The Methylenation of Catechols, J. Chem. SOC. (C), 1969
He talks about the formation of byproducts, and adds the catechol and NaOH to the solvent mixture.
[Edited on 11-11-2009 by mr.crow]
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Sedit
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To prevent loss after 10 downloads I saved it to my site and linked it.
File secured....
http://www.thevespiary.org/sedit/Chemistry%20-%20Organic/met...
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Nicodem
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Always check the original source when uncertain. In that review, there is no claim of the reaction rate being measured at reflux temperature.
Moreover, in the table the temperature of 170°C is explicitly mentioned, which means the kinetic measurement with ethanol/water solvent was done in a
closed vessel (see J. Org. Chem., 36, 2196-2199). The authors of the paper did not find any clear correlation of the reaction rate with the
solvent polarity. Instead they found out the best solvents are those that are more acidic and/or more protic. This is not even surprising given that
acid catalysed aromatic Claissen rearrangement (for example catalysed with BCl3) occurs at -40 to 0°C (which is a 10 magnitudes reaction rate
increase; see Helvetica chimica acta, 56, 14-75). Anyway, all this is pointless as the most practical way of doing a thermal aromatic Claisen
rearrangement is by doing it solventless. The reaction is over in few minutes at 200-220°C and all there is to do is take care the exotherm does not
increase the temperature too high (thus oil bath and slow heating!).
The papers you downloaded from this forum need not to be uploaded again. You can just post the link to the thread where you found them. For example:
Methylenation of catechol derivetives (Base cataylized)
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mr.crow
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Thanks Nicodem, Im a total noob when it comes to sources
That is indeed where I found the paper from, but forgot.
According to the book the claisen reaction does in fact work with ethanol at reflux temperature, but only for catechol mono-allyl ether and a base
catalyst. This is clearly not the case for benzylchloride1's compound though.
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benzylchloride1
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I am sorry for not getting to this sooner. Here is the corrected ISIS draw flow chart of the synthesis. I accidently forgot the whole part with the
Clasien rearrangement; my mistake. The procedure uses potassium tert-butoxide in dimethyl sulfoxide for the rearrangement reaction. I am going to try
sodium isoprpoxide which can be madeby drying 2-propanol with sodium hydroxide and distilling. It is not very pure, but it is a much stronger base
then just sodium hydroxide and small quantites dissolve in water with a hissing sound and the solid has a slight odor of isopropanol, even though it
is bone dry in appearance. I will post the infrared spectrum I ran of the 1,2-methylenedioxybenzene as soon as I have a chance. I am debating what to
do as far as the reduction of the nitro compound. I could use the procedure in Organic Syntheses Collective volume II where nitro compounds are
reduced with iron in an alcoholic solution, after the reduction, the solution is filtered from the iron and concentrated, leaving the amine or use
hydrazine dissolved in 2-propanol as the reducing agent. When I tried to nitrate 1,2-methylenedioxybenzene in a acetic acid, sulfuric acid mixture in
the cold, a purple mixture resulted after adding ice cold sulfuric acid to the solution of the methylenedioxybenzene in acetic acid. This indicated to
me that the formaldehyde ketal was hydrolyzed, producing catechol, which subsequently formed a carbo ation in the highly acid solution giving rise to
the intense dark purple color. After adding the nitric acid and working up the mixture, no solid was obtained, every thing had dissolved in the water
used for the work up, forming a dark brown solution. The nitration with acetic acid, nitric acid and an acetic anhydride works wonders. Actic
anhydride is very easy to make and using it in this synthesis should raise no objections. I am also going to investigate some methods of catechol
methyleneationthat use phase transfer catalysts, as I need around 50 more grams of the 1,2-methylenedioxybenzene. I will probably only obtain a gram
or less of product if every thing works well.
[Edited on 13-11-2009 by benzylchloride1]
Attachment: Carpanone Synthesis.skc (11kB)
This file has been downloaded 841 times
[Edited on 13-11-2009 by benzylchloride1]
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Nicodem
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There's not much I can comment on your ambitious plans except good luck and a couple of trivial remarks:
Personally I think you will be sorry for choosing Fe + HCl as a reduction system. Sounds like lots of dirty work.
Using Na2CO3 as a base in the O-allylation of sesamol also sounds like a very bad idea if you value your starting material. Use dried and finely
ground K2CO3 in acetonitrile or acetone. Alternatively use KOH in ethanol. Is there a reason why you don't want to follow a literature example here? I
would be wandering the same about the nitro reduction, but I guess in that case you are limited by reagent choice. But surely you don't have troubles
obtaining K2CO3?
Quote: Originally posted by benzylchloride1  | | The procedure uses potassium tert-butoxide in dimethyl sulfoxide for the rearrangement reaction. I am going to try sodium isoprpoxide which can be
madeby drying 2-propanol with sodium hydroxide and distilling. It is not very pure, but it is a much stronger base then just sodium hydroxide ...
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I think you got it wrong. NaOH in DMSO is a considerably stronger base NaOiPr in DMSO (just compare the pKa's of H2O and iPrOH in DMSO: 31.2 vs. 29.3;
and t-butoxide is approximately equally basic as isopropoxide: pKa 29.4). I think your misconception of basicity comes from your comparison with water
as solvent which is something completely different. Water molecules solvate anions while DMSO does not (always keep this in mind with aprotic
solvents!). Therefore the more hydrophilic the anion, the more basic it is in DMSO compared to H2O as solvent. For example in water hydroxide is a
weaker base than ethoxide, but in ethanol as solvent it is the opposite (hydroxide is as stronger base there than ethoxide is!).
Of course, with less polar solvents one must not ignore the effect of the counterion which is something that you can often ignore with water as
solvent. For example, in water, LiOH, NaOH, KOH, RbOH and CsOH are all practically equally potent bases (the acidity of cations in water can be
neglected due to a very efficient solvation), but in other solvents this is not true any more. There the basicity increases from LiOH to CsOH. So if
you compare NaOH vs. tBuOK in DMSO, then they might be similarly strong bases, but if you compare KOH with tBuOK in DMSO, then KOH is stronger.
In this particular case tBuOK is only used out of convenience, simply because it is ubiquitous in organic labs, it dissolves in DMSO without problems
(unlike KOH which takes ages), and moreover it allows the experimenter not to be bothered with a theory he does not fully understand.
My advice is therefore not to bother with isopropoxides and such. Just use KOH, which is the most commonly used base for base catalysed double
isomerizations anyway.
| Quote: | | Here is the corrected ISIS draw flow chart of the synthesis. |
For being internet user friendly, I seriously think most people better appreciate a normal GIF attachment of a scheme so that it does not require
external software like ChemSketch. Like this:
[Edited on 15/11/2009 by Nicodem]
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benzylchloride1
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Nicodem, thanks for your help on this synthesis. I am considering using a catalyzed hydrazine reduction of the nitro compound, since the reduction
with iron would probably lead to a mess. I am planning on using potassium hydroxide as the base for the ether synthesis and the isomerization of the
double bond since I have plently of it. I ran a half scale methylenation of catechol, adding a solution of catechol in DMSO, along with a suspension
of sodium hydroxide to a refluxing solution of dichloromethane in DMSO, after steam distillation, extract with DCM, drying and removal of the solvent,
around 40g of 1,2-methylenedioxybenzene was left. I started from 55g of catechol, so the yield was 70%. I nitrated 20 g of the
1,2-methylenedioxybenzene with 75 ml glacial acetic acid, 10 ml 70% nitric acid and 2.0 ml acetic anhydride catalyst. The product precipitated as a
tannish crystalline material. The product was then recrystallized from methanol. It is currently drying a room temperature. The product from a 2 g
scale nitration by the same method melted at 147 degrees Celsius, which is the same as the literature melting point. I will be running test reduction
of the nitro compound this week. I am afraid that the hydrolysis of the diazonium salt to the phenol will give a very low yield of the desired
product, sesamol, 4-hydroxy-1,2-methylenedioxybenzene. I have converted aniline to phenol by this method, with 40% yields. Is there any way of
increasing the yields of this reaction?
[Edited on 16-11-2009 by benzylchloride1]
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Arrhenius
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I was going to suggest SnCl2*2H2O mediated reduction of the nitro group, because it's quick and easy. But it requires >3eq to fully reduce the
nitro group. Yields are typically 80-100%. If you have the means, catalytic hydrogenation is probably the best option.
Well, now that I've looked up the price, the tin(II) chloride method looks a quite reasonable. If you use ~4eq tin, and 1eq HCl, the reaction should
go in about 15-30 minutes at room temp. If you want, I'll look in my notebooks for a procedure.
[Edited on 16-11-2009 by Arrhenius]
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sonogashira
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| Quote: Originally posted by benzylchloride1 | I am afraid that the hydrolysis of the diazonium salt to the phenol will give a very low yield of the desired product, sesamol,
4-hydroxy-1,2-methylenedioxybenzene. I have converted aniline to phenol by this method, with 40% yields. Is there any way of increasing the yields of
this reaction?
[Edited on 16-11-2009 by benzylchloride1] |
Maybe you can try (instead of nitration) bromination and Cu(I) catalysed addition of OH?
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benzylchloride1
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The nitrated product weighed 20 grams, for a percentage yield of 75%, based on 1,2-methylenedioxybenzene. Infrared spectra of
1,2-methylenedioxybenzene, and 4-nitro-1,2-methylenedioxybenzene taken with my new spectrophotometer are attached in PDF format. You will have to
select a program that can open PDF files on your computer in order to open these files.
Attachment: IR of 1,2-methylenedioxybenzene (1.2MB)
This file has been downloaded 689 times
Attachment: IR of 4-nitro-1,2-methylenedioxybenzene (1.1MB)
This file has been downloaded 668 times
[Edited on 17-11-2009 by benzylchloride1]
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Nicodem
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Somehow you managed to lose the .pdf extensions in the attachments, so those trying to open them should either specify Adobe Reader as the program to
open them or to save them renaming them by adding the .pdf.
The IR look fine. 1,3-Benzodioxole corresponds to the spectra at SDBS. So does the spectra of the nitro derivative.
Congratulations, two out of many steps are done. 
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unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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benzylchloride1
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A synthesis progress report:
The reduction of 4-nitro-1,2-methylenedioxybenzene in 2-propanol with iron filings and hydrochloric acid was successful. Around a 60% yield of the
(3,4-methylenedioxy)aniline was obtained after redistillation of the crude product. The product was slightly yellow in color and would crystallize
after standing in a cold room for several hours. The infrared spectrum of the product matched the reference spectrum on the Aldrich website. The
diazotization and hydrolysis of the diazonium salt with a large excess of copper (II) nitrate was unsuccessful; upon steam distillation of the
reaction mixture, a yellow crystalline material was obtained that did not melt below 100 C; and the IR spectrum did not match the Aldrich reference
spectrum for sesamol. I am working on the bromination of 1,2-methylenedioxybenzene with sodium bromide, ammonium persulfate in methanol, catalyzed by
a small quantity of sulfuric acid. Does any one have a procedure for the copper (I) catalyzed hydrolysis of aryl bromides? I have also completed the
synthesis of the allyl bromide required for the Williamson ether synthesis. I synthesized allyl alcohol via the method in Vogels Textbook by the
dehydration of glycerin with formic acid; the method works extremely well, but much of the alcohol is lost in purification. Allyl alcohol is one of
the most unpleasant chemicals I have ever worked with! I synthesized the allyl bromide by distilling a mixture of allyl alcohol, constant boiling
hydrobromic acid and sulfuric acid. The procedure can be found in Vogel and gives around an 80% yield of the allyl bromide.
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Sedit
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Benzylchloride do you have a reference by any chance on the use of Cu(NO3)2 for the formation of diazonium salt?
[Edit]
Im assuming you are speaking of this correct? The use of the Cu(II) to form the phenol FROM the diazonium ion.
[Edited on 11-12-2009 by Sedit]
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Arrhenius
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For direct hydroxylation of aryl halides see:
Tetrahedron (2006) 62(19) 4728-4732 (microwave conditions)
Angewandte Chemie International Edition (2009) 48(46), 8729-8732 (Cu(I) cat., phen (ligand), KOH)
Angewandte Chemie International Edition (2009) 48(46), 8725-8728.
This last one is probably your best bet, as they show numberous beta-diketone ligands that work. They also show proline as a ligand (70% yield), but
with CsOH as the hydroxide source. Other examples shown use KOH.
Here's the supporting info on that paper: http://www3.interscience.wiley.com/cgi-bin/fulltext/12264930...
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Vogelzang
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| Quote: Originally posted by benzylchloride1 | The nitrated product weighed 20 grams, for a percentage yield of 75%, based on 1,2-methylenedioxybenzene. Infrared spectra of
1,2-methylenedioxybenzene, and 4-nitro-1,2-methylenedioxybenzene taken with my new spectrophotometer are attached in PDF format. You will have to
select a program that can open PDF files on your computer in order to open these files.
[Edited on 17-11-2009 by benzylchloride1] |
The resolution looks pretty good. Even the weak bands show up. What kind of spectrophotometer did you use?
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benzylchloride1
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Here is the reference for the hydrolysis of aryl diazonium salts to phenols using copper (II) nitrate. I currently own a Perkin Elmer 1310 infrared
spectrophotometer; I purchased it off of Ebay recently, the diffraction gratings needed to be realigned. This instrument has a pyroelectric detector
which seldom fails. No replacement thermocouples are available for my Perkin Elmer 467 IR, so I opted to buy a more modern instrument.
Attachment: Hydrolysis of diazonium salts to phenols.pdf (825kB)
This file has been downloaded 1063 times
[Edited on 14-12-2009 by benzylchloride1]
Amateur NMR spectroscopist
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Nicodem
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Too bad the diazonium hydrolysis did not work out. Don't get too frustrated - organic synthesis is all about coping with frustration anyway. You set
yourself a difficult goal and the stage to which you ended up is already a great success.
I did a literature search and this is what I got.
5-amino-1,3-benzodioxole => sesamol
Only one reference in some old and near to impossible to get journal: Malagnini, Armanni, Rendiconti della Soc. chim. di Roma, 5 (1907) 135.
Beilstein gives no details except for "Diazotization" wile I could not locate a CA abstract. If trusting this source it at least appears possible, but
not even the yield is known.
I think your best bet is to use the usual synthesis of sesamol from piperonal. Piperonal can be made by formylation of 1,3-benzodioxole (I would guess
the most amateur friendly method would be using the Duff formylation). Piperonal is then subjected to the Baeyer-Villiger oxidation:
WO2009035652 (with performic acid)
WO2007016431 (with peracetic acid)
Synthetic Communications, 38 (2008) 784-788 or J. Org. Chem., 72 (2007) 10283-10286. (using MCPBA)
There are also many other examples. See also the review in Organic reactions, vol 43 where other references for piperonal BV oxidation can be found.
sesamol => O-allyl-sesamol
With allyl cloride and KOH/ethanol:
Beroza, Journal of Agricultural and Food Chemistry, 4 (1956) 49-52. DOI: 10.1021/jf60059a002
With allyl bromide and K2CO3/acetone:
Devakumar, Saxena, Mukerjee, Agricultural and Biological Chemistry, 49 (1985) 725-730.
Fujimura, Fu, Grubbs, Journal of Organic Chemistry, 59 (1994) 4029-4031. DOI: 10.1021/jo00094a002
Maiti et al. Tetrahedron Letters, 42 (2001) 2389-2392. DOI: 10.1016/S0040-4039(01)00153-8
Kimpe et al. Tetrahedron Letters, 44 (2003) 4199-4202. DOI: 10.1016/S0040-4039(03)00902-X
Petit, Bourgeois, Journal of Chemical Research, Synopses, 3 (2004) 194-195.
Jimenez-Gonzalez et al. Chemistry--A European Journal, 12 (2006) 8762-8769. DOI: 10.1002/chem.200600332
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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