[guy2005]

OK, so I have NO idea how to synthesize this molecule.

Imagine a cyclopentane bonded to an oxygen... That same oxygen is bonded to the second carbon in this chain (CH3-CH-CH2-CH2-O-CH3).  I have to start with mono alcohols of six carbons or less, and I'm allowed to use any reagents or bases I need.

Here's what I was thinking initially.... I was going to use a cyclopentanol, deprotonate that with nBuLi to get a negative oxygen and thus a good nucleophile.  Then I was going to use a four-carbon chain with an alcohol on the second carbon, use SOCl2 to make that OH into a good leaving group (Cl) and use that as my electrophile.  But I have no idea how to get that OCH3 on the end of that chain (we were taught that primary carbo cations are no good).  Any help you guys could give would be great.  Thanks!

[moussa]

I have an idea but not knownig how true is it :
1- ether formation by acting
 CH3-CH2-CH2-CH2-OH +CH3-OH ===> CH3-CH2-CH2-CH2-O-CH3 + H2O
2-USE WITH CYCLO PENTANE A DEPROTONATIONGagent as that you talked about
thus the cylo pentane has a poitive carbocation where oxygen electronpair will attak and thus the your compound will be synthesized

[guy2005]

I don't think that could work....

The cyclopentane is attached to an O ... and that O is attached to a the second carbon in this chain (CH3-CH-CH2-CH2-O-CH3).  I agree with your ether synthesis.... but how can i get that oxygen attached to that second carbon??

[guy2005]

I just wish I knew how to do this.... it's so frustrating!!

[AFFA]

Well, this is my suggested scheme to access the ether compounds. The main drawback is on the Williamson ether synthesis that elimination of cyclopentyl bromide to form cyclopentene would result some side-products. Any other suggestions???

[AFFA]

[movies]

Nice synthesis.  The only problem is that it's hard to do that aldol reaction.  You tend to get polymerization.

How about this:
start with allyl alcohol, epoxidize the alkene with mCPBA.  Open the epoxide with Me₂CuLi, then you have the diol intermediate you have above.

Or better yet, start with crotyl alcohol, epoxidize, and then open the epoxide reductively using Redal, which is selective for the formation of 1,3-diols.

[Hima Potturi]

How about using basic conditions instead of acidic conditions during aldol condensation step? Would that prevent polymerisation?

[AWK]

Yield of aldol addition in basic conditions is over 60%
http://www.freepatentsonline.com:9003/5345004.html

[AFFA]

I think the scheme employing epoxidation and epoxide-ring opening would give the desired diol more chemoselectively comparing to the self-aldol approach. However, the self-aldol approach provide a  much more direct access and it is easily to have scale-up (cheap raw material and no organometallic reagents, e.g. organocupurate and Red-Al required). By the way, it depends on the objective of the synthesis (scale, time and money) for the choice of scheme.

The aldol reaction employing basic condition would result a,b-unsaturated aldehyde as major product while b-hydroxy aldehyde becomes major under acid-catalysis.