Isomerization of conjugated double bond

Recently found an interesting reaction which isomerized the conjugated double bond by the following sequence:
1. ketalize the ketone by acid/ethylene glycol. during which rxn the double bond isomerized to the more substituted position.
2. remove the ketal by oxalic acid which is efficient and mild enough to keep the double bond from isomerization to the more stable conjugated position.

very cool transformations, which demonstrated the author's deep understanding of those reagents and the beauty of organic transformations.
the paper was published about 30-40 years ago in jacs.

Oxidative cleavage of α-hydroxyketones

Tetrahedron Letters 50 (2009) 5399–5402
 "
The oxidative cleavage of vicinal diols, a-hydroxyketones, and related functionalities is a common synthetic procedure and various reagents are available to perform this reaction, such as sodium bismuthate,1 iodo triacetate,2 manganic pyrophosphate,3 KHSO5,4 calcium hypochlorite,5 basic hydrogen peroxide,6 methylrhenium trioxide,7 Bi/O2,8 sodium percarbonate,9 and vanadium-based HPA and dioxygen.10 However, the most versatile reagents for this purpose are sodium metaperiodate,11 and lead tetraacetate.12–14
Usually sodium metaperiodate is used in aqueous solutions, because the effectiveness of this oxidant in organic solvents is very limited due to its insolubility.15 Lead tetraacetate has been used in non-aqueous media to accomplish the same types of reactions effected by periodates with water-soluble compounds.15 On the
other hand, this reagent is difficult to store and handle, non-environmentally friendly and, being more reactive, can afford undesired oxidation byproducts.
Aiming to expand the versatility of sodium metaperiodate as an oxidating reagent in organic media, and to overcome the solubilityissues, variations of a silica gel-supported sodium metaperiodate reagent have been disclosed, to promote oxidative cleavage of 1,2 diols, and oxidation of hydroquinones and sulfur-containing compounds.16–18 Usually the sodium periodate is adsorbed on silica gel, and stirred with the starting material in dichloromethane, ether, or benzene.
"
One of the conditions described in the reference paper (NaIO4/SiO2/toluene) was applied to a mixture of alpha-hydroxyketone and TMS protected alpha-hydroxyketone shown below.
Surprisingly, only alpha-hydroxyketone was cleaved. The TMS protected alpha-hydroxyketone survived.
compared with HIO4 in Et2O, this condition (NaIO4/SiO2/toluene) is more neutral.

A Mask of the More Reactive Carbonyl

David Colby and co-workers from Purdue have just added a useful way to selectively reduce less reactive carbonyls (ie: lactone) over more reactive ones (ie:  ketone) by introducing N,O-dimethylhydroxylamine in the presence of an aluminum reducing agent (DIBAL).

deprotection of dimethyl acetal

1. in a particular substrate bearing a terminal double bond at 5,6 position related to the acetal,
the following deprotection methods failed

Methods tried:                                 results:

1. TFA/water/chloroform                   unknown product, aldehyde/alkene disappeared

2. I2/acetone                                     unknown product, aldehyde/alkene disappeared

3.HCOOH, pentane                          unknown product, aldehyde/alkene disappeared

4. TESOTf, 2,6-lutidine                       no reaction

the following method is successful:

DDQ/MeCN/water rt.

preparation of 2-Bromo-3-(trimethylsillyl)-1-propene

(2-Bromoallyl)trimethylsilane
Expensive.
two methods to prepare it.

1. coupling of 2,3-dibromopropene with a trimethylsilyl organocopper reagent generated by addition
of 1.5 equiv of cuprous cyanide to (trimethylsily1)lithium in a 3:l THF-HMPA mixture at 0 C.
2. Alternatively, the bromosilane was conveniently prepared according to eq 2 in 71% yield. This method has the advantage of avoiding the use of HMPA.

The resulting bromosilane can be distilled and stored in the dark for prolonged periods.

Reference:
J. Am. Chem. SOC. 1991, 113, 7350-7362.

synthesis of cyclopentanones

From:
An efficient one-pot method for the synthesis of mono- and biscyclopentenones via zirconium-catalyzed cycloalumination of cyclic alkynes and diynes, Tetrahedron Letters (2010), doi: 10.1016/j.tetlet.2010.08.120


Cyclopentenones have attracted the attention of organic chemists due to their wide use as building blocks in organic synthesis. In addition, they are often encountered in drugs and flavoring compounds.1

Efficient and widely used procedures for preparing cyclopentenones include the Nazarov cyclization, the
Pauson-Khand reaction and methods based on intramolecular cyclization of dienes, enynes and diynes
catalyzed by Ru, Ir, Rh, Au, Pd or Ni complexes.2
Another method for the synthesis of cyclopentenones
includes intramolecular carbocyclization of aluminacyclopentenes3 generated in situ in Zr-catalyzed
cycloalumination reactions of alkynes and Et3Al (Dzhemilev reaction),4 and their subsequent treatment with
CO2, ClCOOEt or CO(OEt)2.

reference:

1. (a) Surburg, H.; Panten, J. Common Fragrance and Flavor Materials: Preparation, Properties and Uses. Willey&Sons, 2006, pp. 330. (b) Hendrickson, J. B.; Palumbo, P. S. J. Org.Chem. 1985, 50, 2110. (c) Ceccherelli, P.; Curini, M.;Marcotullio, M. C.; Rosati, O.; Wenkert, E. J. Org. Chem.1990, 55, 311. (d) Conti, M. Anti-Cancer Drugs 2006, 17,1017.
2. (a) He, W.; Sun, X.; Frontier, A. J. J. Am. Chem. Soc. 2003,125, 14278. (b) Grant, T. N.; West, F. G. J. Am. Chem. Soc.2006, 128, 9348. (c) Shindo, M.; Yaji, K.; Kita, T.; Shishido,K.; Choueiry, D. Synlett 2007, 1096. (d) Saito, A.; Umakoshi,M.; Yagyu, N.; Hanzawa, Y. Org. Lett. 2008, 10, 1783. (e)Magnus, P. Tetrahedron Lett. 1985, 26, 4851. (f) Deng, L.-J.;Liu, J.; Hung, J.-Q.; Hud, Y.; Chen, M.; Lan, Y.; Chen, J.-H.;Lei, A.; Yang, Z. Synthesis 2007, 2565. (g) Park, K.H.; Song,S.U.; Chung, Y.K. Tetrahedron Lett. 2003, 44, 2827. (h)Shibata, T.; Toshida, N.; Yamasaki, M.; Maekawa, S.;Kagaki, K. Tetrahedron 2005, 61, 9974; (j) Rausch, B.;Gleiter, R. Tetrahedron Lett. 2001, 42, 1651; (k) Gleiter, R.;Schulte, J.H.; Werz, D.B. Eur. J. Org. Chem. 2004, 4077; (l)Oh, C.H.; Karmakar, S. J. Org. Chem. 2009, 74, 370.
3. Negishi, E.; Montchamp, J.-L.; Anastasia, L.; Elizarov, A.;Choueiry, D. Tetrahedron Lett. 1998, 39, 2503.
4. (a) Name Reactions and Reagents in Organic Synthesis.Mundy, B. P.; Ellerd, M. G.; Favaloro, F. G. Jr. Eds. Wiley-Interscience. New Jersey. 2005, pp. 882; (b) Dzhemilev, U.M. Tetrahedron 1995, 51, 4333. (c) Dzhemilev, U. M.Mendeleev Commun., 2008, 18, 1. (d) Dzhemilev, U. M.;Ibragimov, A. G. J. Organomet. Chem., 2010, 695, 1085. (e)D’yakonov, V. A. Dzhemilev Reaction in Organic and
Organometallic Synthesis, New-York.: NOVA Sci. Publ.,2010. p. 96.

activation of Magnesium for grignard reaction

Grignard: Initiating the reaction is the tricky part, people have used 1,2-dibromomethane, iodine, TMSCl - but for me the best working initiation technique is to place few equivalents of Mg turnings into an oven-dried flask with a large egg-shaped stirbar, flush it thoroughly with dry argon, add few drops of Br2 and dry-stir the Mg turnings in the Br2 vapors overnight. Then add freshly distilled ether solvent via canula (the bromine color disappears) and then carefully your substrate. I got some Grignards like BrMg(CH2)3MgBr by this technique that are hard to make by other methods (unless you want to mess with Rieke Mg). The Mg turnings are fairly fragile and crushing them in oxygen-free and nitrogen-free environment uncovers a highly-reactive newly-formed surface which is further protected by MgBr2 formation. MgBr2 is soluble in ether. Please note that one has to use Ar because N2 reacts with fresh Mg surfaces, to produce dark Mg nitride.


http://chemknowhow.com/forum/viewtopic.php?t=448

Prepartion of magnesium bromide diethyl etherate solution

Once I was going to make a MgBr2-OEt2 1M solution in Ether.
When the ether was added into MgBr2-OEt2 powder, two layers of liquid was resulted.

Turned out the button layer contains MgBr2 at 39%wt. the top layer contains 3%wt.
addition of some benzene can increase the solubility and make a clear solution.

reference:
digital.library.okstate.edu/OAS/oas_pdf/v32/p79_82.pdf

note:
In a preparation, 1.5 M clear solution was made using 27 ml of Et2O and 4 mL of benzene at 25 C.

Don M. Coltart

http://fds.duke.edu/db/aas/Chemistry/faculty/don.coltart

Assistant professor, Duke
NSERC, AHFMR, and CRI Postdoctoral Fellow, Memorial Sloan-Kettering Cancer Center, 2001–2004
Ph.D. Chemistry, University of Alberta, 2000
M.S. Chemistry, University of Manitoba, 1995
B.S. Biochemistry, University of Manitoba, 1993

Research Interests

Asymmetric α-Alkylation of Ketones via Activated Hydrazones

Direct Carbon-Carbon Bond Formation via Soft Enolization of Thioesters

Natural Products Total Synthesis

A proposal for the synthesis of cortistatin A

The  proposal is as following:

The discussion of key steps:

1. the c-h insertion to form the five-membered ring is well known.

2. The oxygen bridge can then be formed through epoxidation and epoxide ring expantion which might be the biological way also.

3. alternatively the oxygen bridge can be formed by the diazo insertion into C=O and then 3+2 addition.

4.the 7-membered quadene can be constructed by carbene/carbenoid inerstion into aromatic rings followed by elimination of OAc.

Enantioselective Fp mediated alkene addition?

the above reaction is from wiki
http://en.wikipedia.org/wiki/Cyclopentadienyliron_dicarbonyl_dimer


I am just wondering whether it is possible to make it enantioselective?
anyone did it already? not as I know.

A proposal for englerin A synthesis

A hot molecular.
here I proposed a synthesis of Englerin A.

1. it is known we can open the epoxide from the more hindered/more stable site.

2. Single electron reduction then can form the required C-C bond and hopefully set the secondary alcohol.

The starting material can be prepared by C-H insertion. It is known to give trans fused 5,6 rings.

One method to enhance the power of the lab sonicator

Besides of getting a more powerful sonicator, there is a simple method you can try to get more power out of the old sonicator.
the method is described in a journal paper by a Japanese researcher.
The method is simple: just add detergent to the water bath.
The result is substantial.
the reason is ovbious that the polymer has big molecular weight than water so the long-distance energy-transfer-ability is better.

Don't believe ? try it! and post the result here.

Proposal of synthesis of mayamycin

Johannes Imhoff and co-workers at IFM-GEOMAR inn Germany have isolated a polyketide that had an IC50 value of 0.3 micromolar against HT-29 (colon adenocarcinoma) cell lines.

preparation of derivatives of Calicheamicin by enzyme ？

1. The gene for the biosynthesis of calicheamicin is known. As I can remember, the calicheamicinone is constructed and attached to a sugar by an enzyme.
2. Calicheamicin is cheap by biosynthesis. calicheamicinone is difficult to make by chemical synthesis.
3. no known way to cleave Calicheamicinone from calicheamicin.

So is it possible to make new derivatives by mixing a new sugar with calicheamicin in the presense of some enzymes ?

reductive deoxygenation of vinlyl or aryl triflate

Some conditions:

1. pd(PPh3)4/Bu3SnH/THF.
works for vinyl triflate.

2. pd(OAc)2/DPPF/Formic acid/TEA/Bu3SiH/DMF, 50C
works for electron-rich aryl triflate.

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proposal of synthesis of namenamicin

Namenamicin is a enediyne.
the construction of the sulfur-containing quartery center is the critical part of the synthesis. This proposal uses a thionium ion to directly form the quartery center which can lead to the desired structure in an efficient way.

proposal of synthesis of dictyolactone

1.The target is quite an interesting molecular.
2. This proposal mainly aims at the application of C-H insertion in total synthesis.

How to convert indole to tryptamine ?

1. POCl3-DMF to make the indole aldehyde,
2.nitromethane to make unsaturated nitro indole.
3. LAH reduction to give you tryptamine.

to save one step, step 1 and 2 can be made into one step:
TFA, (CH3)2N-CH=CH-NO2, DCM to make the unsaturated nitro indole.

to increase the functional group compatibility of this sequence,
the LAH reduction step can be replaced by a 2 step sequence:
1. NaBH4/SiO2 reduction to take off the double bond.
2. Fe/AcOH reduction to convert the nitro group to amine.

How to reduce 2-oxyindole ?

1. BH3. 0C.
slow reaction, low yielding, but can tolerate many functional groups, like ester.
can over reduced to indoline.

2. LAH
of course, amide can be reduced.

3. triflation first, then Pd/Et3SiH remove triflate.

4. lawesson's reagent to convert oxygen to sulfur, then reduce it by
Raney Ni.

5. some reducing reagent (red-al, super hydride...) under the help of acid (TFA, BF3-OEt2...)

How to prevent N-Cbz from falling off in hydrogenation condition ?

N-Cbz is sensitive to H2/pd/c even in basic condition (TEA).
Known methods to prevent N-Cbz from falling off when doing hydrogenation reactions are not many.

1. Pd/c (en), H2, THF by Kosaku Hirota
pd/c (en) is pd/c deactivated by ethylenediamine. It is developed for chemoselective hydrogenation of reducible functionalities such as olefin, acetylene, nitro, azide, aromatic bromine or benzyl ester moieties, in the presence of O-Bn or N-Z protective
groups.
alkyl N-cbz is stable while double bonds are saturated.
aryl-N-cbz is unstable under this catalyst.
H. Sajiki, K. Hattori and K. Hirota, J. Org. Chem., 1998, 63, 7990.

2. Pd(OAc)2, DPPF,TEA, dmf,formic acid
Can do deoxygenation of phenol by OTf in the presences of N-Zbz.

3. squaric acid derivative/pd/c/H2
works ok, can saturate double bond without touch n-cbz.

4. pd/c/ph2s/H2
also can saturate double bond without touching n-cbz.

5. Pd(OAc)2, DPPF, TEA, dmf,formic acid, Et3SiH
works for deoxygenation of phenol triflate in the presense of N-Cbz.

Note:
1. pd/c(en) was tried. but n-cbz falled off quickly.
2. dppe/pd/formic acid method is OK.
3. ph2s/pd/c/h2 didn't touch N-cbz in my hand. but can't do deoxygenation of a phenol.

Making of N-methyl tryptamine

United States Patent: 4946840

Preparation of 1-methyl tryptamine

This step began with a solution of:

(1) 1.6 g (10 mmol) of tryptamine; and (2) 20 ml of dimethylformamide. This solution was added dropwise to a suspension of: (1) 440 mg (11 mmol) of sodium hydride oil in (2) 30 ml of dimethylformamide. A dark brown solution resulted.

The dark brown solution was then stirred for 30 minutes at room temperature, cooled to 0.degree. C., and mixed with methyl iodide. (The methyl iodide was purified before use by passing it through a column of basic alumina.) After stirring for an hour at room temperature, the reaction mixture was partitioned between ethyl acetate and water. The ethyl acetate layer was washed with saturated brine and then dried by sodium sulfate filtration. The filtrate was concentrated, the filtration residue loaded onto a 5.times.25 cm silicon dioxide column, and the column eluted with dichloromethane:methanol:triethylamine, 95:4:1. Pure fractions were concentrated to afford 970 mg (a 56% yield) of the first intermediate as a yellow oil.

note:
1. usual procedure requires protection of NH2 then alkylation on the indole Nitrogen which is unnecessary if you follow the above procedure.
the reaction works fine although the yield is not high and product separation is difficult.

Sonogashira Coupling

he reaction was first reported by Kenkichi Sonogashira and Nobue Hagihara in 1975.

The coupling of terminal alkynes with aryl or vinyl halides is performed with a palladium catalyst, a copper(I) cocatalyst, and an amine base. Typically, the reaction requires anhydrous and anaerobic conditions, but newer procedures have been developed where these restrictions are not important.


solvent/base : tea or other amine, DMF, MeCN
Pd (0) is needed, pd(pph3)4, also pd (II) can be used which will be reduced to pd (0) by alkyne. pdcl2(pph3)2.
CuI.
some additive can increase the rate and yields: ex. Bu4NI,
temp: rt or heat.

note:
1. electron deficient aromatic halides gave better yields. electron rich aromatics don't react well.

Preparation of 2,3-dihydroxycyclopentanone

The title compound seems easy to make, but actually costs a lot of steps, especially in enantiomeric form.

In the following paper, the auther had a new preparaion method.

Syntheses of (-)-Oleocanthal
by AB Smith III
J. Org. Chem. 2007, 72, 6891-6900

We began by adopting a protocol developed by Borchardt14 et al. (Scheme 6). Exhaustive
oxidation of 16 employing pyridinium chlorochromate (PCC) (4 equiv) provided lactone 17 in 62% yield. This transformation involves both oxidation of the primary alcohol and cleavage of
a C-C bond. Treatment of the resultant lactone (17) with the lithium anion derived from dimethyl methylphosphate produced enone (-)-18, which upon hydrogenolysis furnished ketone (-)- 11. The overall yield of (-)-11 from D-lyxose was reproducibly 50% on a 10 gram scale. Although D-lyxose is more expensive (ca. 3 times) than D-ribose, the starting material utilized in the first-generation synthesis, this sequence eliminates three steps, reduces the use of several expensive reagents, and is scalable. Equally important, only a single chromatographic separation is required after hydrogenolysis. Alkylation as achieved in the firstgeneration synthesis then afforded (-)-12 in 55-60% yield.





















Is the new way really good?
I don't know. But at least there is a big drawback they didn't say it here.
In the experimental, they described the pcc reaction which needs a lot of benzene (cause cancer) as solvent.

Maze Solving by Chemotactic Droplets

a very interesting paper.
in jacs asap.

Solving maze problems is not only relevant to the everyday issues
of urban transportation1 and to experimental psychology2 but is
also one of the model problems of network and graph theory3 as
well as robotics.4 With the advent of computers, algorithms for
maze solving have become automated, but the solution times still
scale unfavorably with maze size/complexity.5 Several groups have
thus explored the possibility of maze solving by physical, chemical,
or even biological systems: microfluidic networks,6 chemical waves7
or plasmas,8 or microorganisms growing in response to food
gradients within the maze.9 Inspired by the latter example, we
wished to create a system in which an inanimate/chemical construct
would be self-propelled and solve mazes in response to chemical
stimuli. Here we describe one such system comprising small
droplets powered by the combination of acid/base chemistry and
surface tension effects. When subject to a pH gradient within a
maze, these droplets move toward regions of low pH and find the
shortest of multiple possible paths. Taxis in our system is over
distances of several centimeters and derives from the convection
flows developed outside of the droplets.1