Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: rita87 on March 01, 2009, 08:02:00 PM
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Hi ,
can anyone help me with the mechanism (with curly arrows)for the following reactions. I know there are many different steps and that's a long question, but i really dont know how it works,couldn't find any usefull sources.
Thank you guys
P.S. this can be found in"Two-directional synthesis. Part 1: A short formal synthesis of (±)-histrionicotoxin and (±)-histrionicotoxin 235A "Tetrahedron Letters ,Volume 41, Issue 47, 18 November 2000, Pages 9163-9165
(http://)
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cool sequence.
3->5, 6->7 are both in the acetal mechanism (the lewis acid changes, but the mechanism doesn't).
5->6 is a variation of the aldol.
7->8 starts with a variation of imine formation, then joins 8->9 as a variation of a Michael addition.
Lots of variations of common reactions... but fortunately the mechanisms are all the same as the common reactions.
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3->5 :I know the mechanism for a normal hydrolysis(HCl in this case) of acetal,but i dont know how it works for the ring.I also don't know what THF does in this mechanism.
Thanks
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THF is solvent only. Tetrahydrofuran.
Cyclic acetals operate exactly the same as 'typical-looking' acetals. Whether the alcohols come from two molecules of methanol or one molecule of ethylene glycol... the mechanism - forward and backward - is exactly the same.
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so is this mechanism correct( I skipped 2-3 steps)
Thanks
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step 1 is good. not sure how you got to step 2, but a) you switched from ethylene glycol to methanol, and (with the carbon chain and proton also on R) carbon has 5 bonds. intermediate 4 is back on track, do you know how to get from int 5->pdt?
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I am not sure if the ring breaks into OMe-R-OMe or O-R-OCH2CH3 .
yes, you are right, C should have 4 bonds it should be R=O-Me.
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products will be ethylene glycol (2 eqiv) and your dialdehyde.
I've redrawn the steps in your mech with what the structures should look like. Can you push the arrows to get through the mech?
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Thanks mazman , yes i know how to draw the arrows.
the only thing i still dont get is that according to the normal mechanism(not cyclic),there should be ROH loss in step 2 . is that different in the cyclic form?
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no different. the R in ROH is just a longer, more complex, carbon chain that's still attached to the molecule. The cyclic acetal is a common protecting group for aldehydes and ketones. It makes the carbonyl carbon no longer electrophilic.
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do you know why ROH stays attached to the molecule, and not lost as in the non cyclic form?
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It doesn't. That's the whole point. There's no difference in the mechanism. The only thing that changes is the carbon chain on the oxygen units. One decomposes to give 2 mono alcohols. One decomposes to give one diol. See spiroketals for another variation for which the mechanism also doesn't change. Those decompose to give one ketodiol.
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thank you sooo much azmanam, you are always a gr8 help. thanks :)
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for 5-> 6 i am using peterson olefination, but i am very confused with different stereoisomers , please can you explain how it works in this case.
I know that depending on acid or base used,elimination will be syn or anti, but dont know if it also effects stereoisomers formed etc.
I am very confused
thanks
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Start here:
http://www.organic-chemistry.org/namedreactions/peterson-olefination.shtm
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Thanks, the link was helpful.
Now i am trying to do 6-> 7 . i know it is hydrolysis and similar to acetal hydrolysis before but the reagents are confusing i don't know which one is the acid, and why we have 3 reagents, and how to use them all.
please can you help me.
many thanks
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i don't either. acetonitrile and water are solvents, for sure.
Silver's the lewis acid... NCS a scavenger for sulfur? I don't know what NCS does.
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I found this mechanism in a paper, does this look correct to u. can i use NCS instead of MNO2 and AgNO3 instead of AlCl3?
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The step 8 :rarrow: 9 is a [3+2] cycloaddition (between a nitrone and "poor electron olefin")
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cool sequence.
3->5, 6->7 are both in the acetal mechanism (the lewis acid changes, but the mechanism doesn't).
5->6 is a variation of the aldol.
7->8 starts with a variation of imine formation, then joins 8->9 as a variation of a Michael addition.
Lots of variations of common reactions... but fortunately the mechanisms are all the same as the common reactions.
I don't understand 5-6.
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Generation of Me3SiCH(Li)CN. Attack to aldehydes. Pettersons-type olefination.
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The step 8 :rarrow: 9 is a [3+2] cycloaddition (between a nitrone and "poor electron olefin")
thanks you, do you have any idea about the regioselectivity in this reaction.
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r u workig from a textbook? if so, which one?
thanks
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Now i am trying to do 6-> 7 . i know it is hydrolysis and similar to acetal hydrolysis before but the reagents are confusing i don't know which one is the acid, and why we have 3 reagents, and how to use them all.
please can you help me.
Here's the original reference (subscription needed): http://dx.doi.org/10.1021/jo00822a019
The NCS does indeed 'sequester' the sulfur, so to speak, so that it drives the reaction to the right. In this case, sulfur reagents can be oxidized to a variety of sulfur oxidation states by chlorine.
Even more original reference (subscription needed): http://dx.doi.org/10.1021/jo01208a001
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in the last stage , 8-> 9 i am not sure if this reaction happens in a single step or 2 steps are required. if 2 steps,do you know iwhich bond forms first, O-C or C-C ?
many thanks
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I thought it was 2 steps in my first post, but cundi set me straight. It's a cycloaddition, a pericyclic reaction. It's concerted.
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Now i am trying to do 6-> 7 . i know it is hydrolysis and similar to acetal hydrolysis before but the reagents are confusing i don't know which one is the acid, and why we have 3 reagents, and how to use them all.
please can you help me.
Here's the original reference (subscription needed): http://dx.doi.org/10.1021/jo00822a019
The NCS does indeed 'sequester' the sulfur, so to speak, so that it drives the reaction to the right. In this case, sulfur reagents can be oxidized to a variety of sulfur oxidation states by chlorine.
Even more original reference (subscription needed): http://dx.doi.org/10.1021/jo01208a001
OMG, I read the references, thank you but it confused me even more. i don't get this at all, the mechanisms in them are different from what i have.
please could you explain this abit more.
Thank you
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mmm.... no. no, I cant... I don't follow the mechanisms so much either.
What I think is important, as far as this question is concerned, is that you can use silver nitrate and water to deprotect a dithiane to give the desired ketone. The NCS is an additive to react with the sulfur chemoselectively to transform the mercaptan to something that can no longer participate in the reverse reaction (thus driving the reaction to completion). Often, mercury is used for sulfur sequestration purposes, but not so much anymore for obvious reasons. It seems that sulfoxides and sufonyl chlorides are the main product of these oxidations, but would likely be hydrolyzed on workup. The mechanism is probably radical in nature and probably not well understood.
What I would take away from it is an unusual set of conditions for the deprotection of a dithiane. The mechanism, as far as I'm concerned, can be drawn the exact same way as typical acid-catalyzed deprotection of an acetal, but with sulfur instead of oxygen and silver instead of a proton. If this is for a class, you should check with your prof.
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No this is an assignment and my prof doesn't help me .
I've drawn a normal hydrolysis reaction but not sure if the Oxygen atom of AgNO3 attacks carbanion?
Thanks
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No. There's water in the reaction system. Ag+ is just a lewis acid (like the proton is a lewis acid), and water is the nucleophile just like in the 'typical' acetal deprotection.
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Hi ,
please can you help me with the mechanism for 7 -> 8, i know it is an oxime formation but i am not sure how to use NH2OH. Hcl and NaOAc in this mechanism.
Thanks,
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btw I know how to do the secont part which is michael addition,but not sure about the first part.
Thank you,
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well, this is what i have done sofar, but don't know if its correct.
(http://)
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You are pretty much correct. Here's a very nice tutorial diagram on oxime formation, and you can even click the second link I've provided and it'll walk you through each step of the process.
http://www.cf.edu/departments/instruction/las/science/chemistry/mechanisms/oxime-mechanism.htm
http://www.cf.edu/departments/instruction/las/science/chemistry/mechanisms/oxime-tut-1.htm
There's this really weird, kinda annoying music playing along too!
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Thanks macman,
I used the same website to draw my mechanism, but i don't know how NAOAc is converted to CH3COOH.
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NaOAc is the sodium salt of acetic acid. OAc an abbreviation for Acetate, which is the conjugate base of CH3COOH.
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Thank you so much macman. :)
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The question doesn't say anything about the presence of Water in 3->5 , is that possible that THF plays the role of Water here?
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I've tried to draw it using THF as nucleophile but I don't know how to do it as it doesn't have H attached to O.
Can someone help me please.
Thanks
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2M HCl is assumed to be in water, unless otherwise specified.
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oooohhhhh, that's right. Thank you sooooo much