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.
Showing posts with label methodology. Show all posts
Showing posts with label methodology. Show all posts
Saturday, September 11, 2010
Saturday, July 11, 2009
synthesis of the highly strained 3-aza-[7]-paracyclophane core of haouamines
by Pete Wift
organic letters 2006 1901.
failed methods:
1. various macrolactamization conditions (Scheme 1).
2. synthesis of medium-ring biaryl compounds by organocuprate oxidation also failed (Scheme 2).
3. ring contraction strategy. (Scheme 3)
finally successful method:
As an alternative to the more traditional strategies for overcoming the kinetic barriers of ring closure, we envisioned the preparation of a macrocyclic ring composed of a tetrahydro derivative and subsequently an introduction of the ring strain by altering the hybridization of C from sp3
to sp2 by elimination of methanol. Tautomerization to the phenol would result in the formation of the biaryl system(Scheme 4).
Interestingly, this paper came out about the same time as Baran's first total synthesis (receive date).
organic letters 2006 1901.
failed methods:
1. various macrolactamization conditions (Scheme 1).
2. synthesis of medium-ring biaryl compounds by organocuprate oxidation also failed (Scheme 2).
3. ring contraction strategy. (Scheme 3)
finally successful method:
As an alternative to the more traditional strategies for overcoming the kinetic barriers of ring closure, we envisioned the preparation of a macrocyclic ring composed of a tetrahydro derivative and subsequently an introduction of the ring strain by altering the hybridization of C from sp3
to sp2 by elimination of methanol. Tautomerization to the phenol would result in the formation of the biaryl system(Scheme 4).
Interestingly, this paper came out about the same time as Baran's first total synthesis (receive date).
Wednesday, June 24, 2009
an interesting paper from Eun Lee
A Carbonyl Ylide Cycloaddition Approach to Platensimycin
Lee, Kim, Jang, Choi and Chung. ACIEE, 2008,
why interesting?
"they knew that a terminal olefin would have the incorrect electronic configuration to lead to the desired product in the [3+2] before attempting the chemistry. However, they did the reaction anyway, and ended out with a cracking yield of the wrong isomer and only a trace of the desired. Playing with the HOMO coefficient by using a vinyl halide in place of the terminal olefin allowed the chemistry to proceed in a tasty 83% yield, with small amounts of the competing products."
from http://totallysynthetic.com/blog/?p=976
Lee, Kim, Jang, Choi and Chung. ACIEE, 2008,
why interesting?
"they knew that a terminal olefin would have the incorrect electronic configuration to lead to the desired product in the [3+2] before attempting the chemistry. However, they did the reaction anyway, and ended out with a cracking yield of the wrong isomer and only a trace of the desired. Playing with the HOMO coefficient by using a vinyl halide in place of the terminal olefin allowed the chemistry to proceed in a tasty 83% yield, with small amounts of the competing products."
from http://totallysynthetic.com/blog/?p=976
Friday, January 30, 2009
The Hydrolytic Kinetic Resolution – Jacobsen’s Catalyst
An Introduction
Enantiomerically pure epoxides are extremely valuable
chemical compounds due to controllable but high reactivity of
epoxides coupled with the vast array of reactions they can
undergo with retention of stereochemical integrity. One can
envision a number of direct routes to asymmetric epoxides
(Figure 1). Asymmetric carbene addition has never achieved
broad applicability due to both the instability of the carbenes,
low yields and low enantioselectivities. The most common
methods for epoxide formation is controlled addition of
activated oxygen to an alkene. For some olefins, this process
can be made enantioselective, an achievement for which K.
Barry Sharpless was awarded 1/2 of the Nobel prize in 2001.
The Sharpless asymmetric epoxidation is restricted to internal
olefins with pendent functionality such as an alcohol which
helps direct the reaction. In 1990, Jacobsen, fresh of a postdoc with Sharpless and at the beginning of his
independent career at UIUC, introduced a system which obviated the use of a directing group, but the
enantioselctivies were not phenomenal and yields were not spectacular. Furthermore, terminal olefins were still
difficult. Simultaneously and independently, Katsuki (a Sharpless postdoc from ten years prior) revealed a
closely related system which suffered the same drawbacks.
In the mid 1990’s, having moved to Harvard, Jacobsen
was exploring the use of a variety of metal catalysts all based
around a chiral “salen” ligand scaffold (Figure 2). The first
breakthrough came with the desymmetrization of meso
epoxides with Me3SiN3 catalyzed by a complex where M =
CrCl (Figure 3). While it is generally easily controlled on the
laboratory scale, the potentially explosive nature of Me3SiN3
makes it a poor choice for industrial processes. Furthermore, the resolution of terminal epoxides remained
elusive. Thus the search of a better both a better catalyst and a better nucleophile continued. The hydrolytic
kinetic resolution (Figure 3) was discovered due to a fortunate accident. Jacobsen had been working with a
reduced for of a chromium-salen complex. Surprisingly, 1,2-epoxyhexane (Figure 3, R = n-Bu) proved to be an
extraordinarily good substrate. Furthermore, the
solid residue isolated from the end of reactions
with that substrate worked extraordinarily well to
resolve others! Careful investigation led to the
discovery that acetic acid, left from the industrial
synthesis of epoxyhexane, had served to catalyze
the air-oxidation of the metal, increasing the activity of the catalyst. At long last, enantiomerically pure terminal
epoxides were readily available through a simple two step process – epoxidation of a terminal olefin and
selective hydrolysis of one enantiomer of the resulting epoxide. This was an event dramatic enough to warrant
publication in Science, an extreme rarity for a synthetic methodology.
Jacobsen has proceeded to exploit this ligand framework, and some variations on it, to enantioselectively
catalyze a broad range of reactions including an array of nucleophilic epoxide opening reactions,
hydrocyanation of aldehydes and imines, conjugate addition of HCN, aldol variations and Diels-Alder
variations, to name a few. In fact, the ligand shown in Figure 2 has become known simply as “Jacobsen’s
ligand”. The technologies developed in Jacobsen’s lab have been commercialized by Rhodia ChiRex, a joint
venture between Jacobsen and global chemical giant Rhodia. The catalysts have been used in many
pharmaceutical syntheses and, it sometimes seems, by nearly every synthetic organic chemist alive. Other
researchers too numerous to name have also used these ligands and catalysts in developing other reactions too
numerous to count. Truly it is a phenomenal impact for an accidental discovery barely a decade old.
From: http://www.chem.colostate.edu/rovis/
Enantiomerically pure epoxides are extremely valuable
chemical compounds due to controllable but high reactivity of
epoxides coupled with the vast array of reactions they can
undergo with retention of stereochemical integrity. One can
envision a number of direct routes to asymmetric epoxides
(Figure 1). Asymmetric carbene addition has never achieved
broad applicability due to both the instability of the carbenes,
low yields and low enantioselectivities. The most common
methods for epoxide formation is controlled addition of
activated oxygen to an alkene. For some olefins, this process
can be made enantioselective, an achievement for which K.
Barry Sharpless was awarded 1/2 of the Nobel prize in 2001.
The Sharpless asymmetric epoxidation is restricted to internal
olefins with pendent functionality such as an alcohol which
helps direct the reaction. In 1990, Jacobsen, fresh of a postdoc with Sharpless and at the beginning of his
independent career at UIUC, introduced a system which obviated the use of a directing group, but the
enantioselctivies were not phenomenal and yields were not spectacular. Furthermore, terminal olefins were still
difficult. Simultaneously and independently, Katsuki (a Sharpless postdoc from ten years prior) revealed a
closely related system which suffered the same drawbacks.
In the mid 1990’s, having moved to Harvard, Jacobsen
was exploring the use of a variety of metal catalysts all based
around a chiral “salen” ligand scaffold (Figure 2). The first
breakthrough came with the desymmetrization of meso
epoxides with Me3SiN3 catalyzed by a complex where M =
CrCl (Figure 3). While it is generally easily controlled on the
laboratory scale, the potentially explosive nature of Me3SiN3
makes it a poor choice for industrial processes. Furthermore, the resolution of terminal epoxides remained
elusive. Thus the search of a better both a better catalyst and a better nucleophile continued. The hydrolytic
kinetic resolution (Figure 3) was discovered due to a fortunate accident. Jacobsen had been working with a
reduced for of a chromium-salen complex. Surprisingly, 1,2-epoxyhexane (Figure 3, R = n-Bu) proved to be an
extraordinarily good substrate. Furthermore, the
solid residue isolated from the end of reactions
with that substrate worked extraordinarily well to
resolve others! Careful investigation led to the
discovery that acetic acid, left from the industrial
synthesis of epoxyhexane, had served to catalyze
the air-oxidation of the metal, increasing the activity of the catalyst. At long last, enantiomerically pure terminal
epoxides were readily available through a simple two step process – epoxidation of a terminal olefin and
selective hydrolysis of one enantiomer of the resulting epoxide. This was an event dramatic enough to warrant
publication in Science, an extreme rarity for a synthetic methodology.
Jacobsen has proceeded to exploit this ligand framework, and some variations on it, to enantioselectively
catalyze a broad range of reactions including an array of nucleophilic epoxide opening reactions,
hydrocyanation of aldehydes and imines, conjugate addition of HCN, aldol variations and Diels-Alder
variations, to name a few. In fact, the ligand shown in Figure 2 has become known simply as “Jacobsen’s
ligand”. The technologies developed in Jacobsen’s lab have been commercialized by Rhodia ChiRex, a joint
venture between Jacobsen and global chemical giant Rhodia. The catalysts have been used in many
pharmaceutical syntheses and, it sometimes seems, by nearly every synthetic organic chemist alive. Other
researchers too numerous to name have also used these ligands and catalysts in developing other reactions too
numerous to count. Truly it is a phenomenal impact for an accidental discovery barely a decade old.
From: http://www.chem.colostate.edu/rovis/
Tuesday, November 11, 2008
Intramolecular epoxide openings
From :
Douglass F. Taber,* Lee J. Silverberg, and Edward D. Robinson
J. Am. Chem. SOC. 1991,113,6639-6645
1. nitrile anion opening and sulfone anions.
2.Nucleophilic allylic silanes have been employed, under acid-catalyzed conditions, ln
intramolecular epoxide openings.
3. Finally, StorkM has shown that ketone and ester enolates can be used to open allylic epoxides,
to form cyclohexane derivatives.
4. The only other enolate-based opening of an epoxide has been that reported by Negishi.31
(31)Z hang, Y.;M iller, J. A.; Negishi, E.-I.J . Org. Chem. 1989,54,2 043.
Douglass F. Taber,* Lee J. Silverberg, and Edward D. Robinson
J. Am. Chem. SOC. 1991,113,6639-6645
1. nitrile anion opening and sulfone anions.
2.Nucleophilic allylic silanes have been employed, under acid-catalyzed conditions, ln
intramolecular epoxide openings.
3. Finally, StorkM has shown that ketone and ester enolates can be used to open allylic epoxides,
to form cyclohexane derivatives.
4. The only other enolate-based opening of an epoxide has been that reported by Negishi.31
(31)Z hang, Y.;M iller, J. A.; Negishi, E.-I.J . Org. Chem. 1989,54,2 043.
Wednesday, August 13, 2008
Intermolecular Enolate Heterocoupling
ASAP J. Am. Chem. Soc., ASAP Article, 10.1021/ja804159y
Web Release Date: August 5, 2008
The direct, convergent synthesis of unsymmetrical 2,3-disubstituted-1,4-dicarbonyl compounds from two carbonyl subunits has proven extremely difficult, several methods for the synthesis of hypothetical succinate 1 are depicted in Figure 2.9,
Efficient, enantioselective syntheses of such entities have escaped synthetic grasp, in spite of their presence in countless natural products and innumerable medicinal remedies. All of the methods depicted suffer from one or more of the following limitations: multistep sequences, installation of requisite disposable functionality on one or both of the monomers, and stereoselectivity problems with prefunctionalization methods and/or during the union of the two monomers. No stereoselectivity was observed or necessary for the most efficient of these methods, the Stetter reaction, as the product was subjected to a pyrrole synthesis. This report is a full account of a research program initiated originally to eliminate the first two of these issues and having since evolved to address the third. By taking advantage of an underutilized and underappreciated reactivity of carbonyl enolates, the oxidative heterocoupling of two enolates joins two different sp3-hybridized carbon centers in a single step without requiring prefunctionalization of the corresponding monomers.
Thursday, July 17, 2008
Bisoxazoline ligands
http://en.wikipedia.org/wiki/Bisoxazoline_ligand
very good article about this kind of popular ligands.
very good article about this kind of popular ligands.
Friday, April 18, 2008
one carbon elongation
1. aldehyde to aldehyde
step 1. aldehyde + PPh3Cl-CH2OMe/t-BuOK
step 2. Formic acid.
Wiki is a good source of infomation:
step 1. aldehyde + PPh3Cl-CH2OMe/t-BuOK
step 2. Formic acid.
Wiki is a good source of infomation:
Examples of homologation reactions include:
- Seyferth-Gilbert homologation
- Displacement of a halide by a cyanide group, which can be reduced to an amine, see: Kolbe nitrile synthesis
- Kiliani-Fischer synthesis, where an aldose molecule is elongated through a three-step process consisting of:
- Nucleophillic addition of cyanide to the carbonyl to form a cyanohydrin
- Hydrolysis to form a lactone
- Reduction to form the homologous aldose
- Wittig reaction of an aldehyde with methoxymethylenetriphenylphosphine, which produces a homologous aldehyde.
- Arndt-Eistert synthesis is a series of chemical reactions designed to convert a carboxylic acid to a higher carboxylic acid homologue (ie. contains one additional carbon atom)
- Kowalski ester homologation, an alternative to the Arndt-Eistert synthesis. Has been used to convert β-amino esters from α-amino esters through an ynolate intermediate.[2]
Some reactions increase the chain length by more than one unit. For example, the following are considered two-carbon homologation reactions:
- Nucleophilic addition to ethylene oxide, resulting in a ring-opening and producing a primary alcohol with two extra carbons.
- Malonic ester synthesis, which produces a carboxylic acid with two extra carbons.
Wednesday, April 16, 2008
Catalytic Activation of the Leaving Group in the SN2 Reaction
They had very good idea here.
the mechanism proposed:
Sunday, March 30, 2008
sacrificing ester
The idea of sacrificing ester.
NaH or KH usually contains some NaOH/KOH which will hydrolyze esters.
Trace of water can also react with KH/NaH to form NaOH/KOH.
a non enoliazable ester can be used to remove the metal hydroxide.
methylbenzoate works fine.
NaH or KH usually contains some NaOH/KOH which will hydrolyze esters.
Trace of water can also react with KH/NaH to form NaOH/KOH.
a non enoliazable ester can be used to remove the metal hydroxide.
methylbenzoate works fine.
Saturday, January 5, 2008
Diastereoselective Intermolecular Pauson-Khand Reactions of Chiral Cyclopropenes
Joesph M. Fox of University of Delaware.
1. the unusual reactivity of cyclopropenes can increase the scope and utility of intermolecular Pauson-Khand reactions.
2. The well-defined chiral environment of cyclopropenes has a powerful influence on the diastereoselectivity of the reactions
and leads to the production of a single cyclopentenone in each of the described cases.
3. The cyclopropane ring strongly influences the stereochemistry of reactions at the enone
4. the three-membered ring can subsequently be cleaved under mild conditions.
5. Notably, the types of products that are accessible via cyclopropene Pauson- Khand/reductive cleavage complement those that can be formed using directed Pauson-Khand methodology
.
1. the unusual reactivity of cyclopropenes can increase the scope and utility of intermolecular Pauson-Khand reactions.
2. The well-defined chiral environment of cyclopropenes has a powerful influence on the diastereoselectivity of the reactions
and leads to the production of a single cyclopentenone in each of the described cases.
3. The cyclopropane ring strongly influences the stereochemistry of reactions at the enone
4. the three-membered ring can subsequently be cleaved under mild conditions.
5. Notably, the types of products that are accessible via cyclopropene Pauson- Khand/reductive cleavage complement those that can be formed using directed Pauson-Khand methodology
.
Tuesday, January 1, 2008
Pd-Catalyzed alpha-Arylation of Trimethylsilyl Enol Ethers with Aryl Bromides and Chlorides
By John F. Hartwig, Angewandte Chemie International Edition, 2006, 5852-5855
1. these conditions allow the coupling of bromoarenes with functionalities that are not tolerated by the basic alkali-metal enolates.
2. Entry 3, 6 showed this method has very good regioselectivity.
Saturday, November 10, 2007
chiral pool
1.Evans Oxazolidinone Auxiliaries
2. menthol, camphor, amino acid derivatives.
3. Myers Pseudoephedrine Auxiliaries
2. menthol, camphor, amino acid derivatives.
3. Myers Pseudoephedrine Auxiliaries
Monday, October 8, 2007
cationic cyclization
initiator:
alcohol,alkene,
epoxide, ketone, ketal,
acid, acid chloride,
C=N+ -> N-C+
R-SO2Ph, R-NO2,
terminator:
alcohol,
azide, ketone, ketal, ester, beta-ketoester.
Enone, TMS enone ether, allyl silane
acytylene
alkene, C=NR,
aromatic, indole
a very good pdf about cationic cyclization:
http://cmds.kaist.ac.kr/skim/lecture/1.Cationic.pdf
alcohol,alkene,
epoxide, ketone, ketal,
acid, acid chloride,
C=N+ -> N-C+
R-SO2Ph, R-NO2,
terminator:
alcohol,
azide, ketone, ketal, ester, beta-ketoester.
Enone, TMS enone ether, allyl silane
acytylene
alkene, C=NR,
aromatic, indole
a very good pdf about cationic cyclization:
http://cmds.kaist.ac.kr/skim/lecture/1.Cationic.pdf
Saturday, October 6, 2007
HMPA
polar aprotic solvent.
1. can chelate with Li, improves basicity of LDA.
also increase the stability of LDA. ( without hmpa, LDA in THF became gray above 0C. with HMPA, LDA in THF can go beyond 0C.)
2. can chelate with Cu for 1,4 addition.
very useful.
1. can chelate with Li, improves basicity of LDA.
also increase the stability of LDA. ( without hmpa, LDA in THF became gray above 0C. with HMPA, LDA in THF can go beyond 0C.)
2. can chelate with Cu for 1,4 addition.
very useful.
organomagnesium
less basic than organolithium?
usually stable in THF at rt. Can be made in reflux THF or ether.
1,2 addition. (for enolizable/stericly hindered ketones, use CeCl3)
To initiate the reaction between halides and Mg,
1. heat,
2. I2 can be used.
3. broken glass can also be used.
4. distill organohalides with CaH2 can also help.
Reaction is very exothermic.
usually, Grignard made from RBr is more reacitive than RCl.
usually stable in THF at rt. Can be made in reflux THF or ether.
1,2 addition. (for enolizable/stericly hindered ketones, use CeCl3)
To initiate the reaction between halides and Mg,
1. heat,
2. I2 can be used.
3. broken glass can also be used.
4. distill organohalides with CaH2 can also help.
Reaction is very exothermic.
usually, Grignard made from RBr is more reacitive than RCl.
organolithium reagent
1. vinyl lithium can't be made directly. tetravinyltin was used to make vinyllithium.
2. RLi is not stable in THF at rt, so Et2O was used as the solvent. control temp at 0C or lower.
3. High sodium Li metal is more active than low sodium Li.
4. Argon should be used instead of N2 when store Li wire in bottle, since Li can react with N2.
5. Excess Li can be used and CuCN can be added directly into the reaction mixture containing Li at -40C. The Cu+ won't be reduced by Li metal.
6. broken glass can be added with Li to improve reactivity. it works as a Li surface scratcher.
7. alky lithium is very basic, stable temp is lower than vinyl lithium.
2. RLi is not stable in THF at rt, so Et2O was used as the solvent. control temp at 0C or lower.
3. High sodium Li metal is more active than low sodium Li.
4. Argon should be used instead of N2 when store Li wire in bottle, since Li can react with N2.
5. Excess Li can be used and CuCN can be added directly into the reaction mixture containing Li at -40C. The Cu+ won't be reduced by Li metal.
6. broken glass can be added with Li to improve reactivity. it works as a Li surface scratcher.
7. alky lithium is very basic, stable temp is lower than vinyl lithium.
Cu mediated 1,4 and 1,5 addition
1. 1,5 addition means opening of cyclopropane conjugated with a beta-ketoester.
organocupper made by organolithium works better than organocupper made by organomagnesium halide. The reason is believed that the Li can chelate with oxygen.
Cu2R made by MgR gives only 1,2 addition while Cu2R made by RLi only gives 1,5 addition.
R is 1-bromo-2-methylpropene. reaction condition: R, Li,broken glass,Et2O, 0C, then -40C, THF,HMPA,CuCN, substrate.
half eq. of CuCN is used to make the active Cu2R.
1. dummy ligand can be used to save half the bromide.
organocupper made by organolithium works better than organocupper made by organomagnesium halide. The reason is believed that the Li can chelate with oxygen.
Cu2R made by MgR gives only 1,2 addition while Cu2R made by RLi only gives 1,5 addition.
R is 1-bromo-2-methylpropene. reaction condition: R, Li,broken glass,Et2O, 0C, then -40C, THF,HMPA,CuCN, substrate.
half eq. of CuCN is used to make the active Cu2R.
1. dummy ligand can be used to save half the bromide.
Monday, September 3, 2007
CeCl3 assisted Grignard rxn
Organomagnisum compound can react with CeCl3 to form some complex so the basisity is reduced.
both hinded and enoliazable ketones can be reactive under CeCl3.
1,2 addtion in most of the cases.
CeCl3 drying process: 90C 4hr, 140-150C 2hr under high vacuum. (0.1-0.2 Torr)
several conditions available:
1.CeCl3/THF
sonication is better than stirring, 1 hr at rt is good enough.
grignard added into CeCl3 at -78C, then ketone.
2.CeCl3 with TiCl4
Even beta-ketone ester can be alkylated to the the beta-alcohol ester! Only successful when gama position is phenyl.
3.CeCl3.2xLiCl in THF
both hinded and enoliazable ketones can be reactive under CeCl3.
1,2 addtion in most of the cases.
CeCl3 drying process: 90C 4hr, 140-150C 2hr under high vacuum. (0.1-0.2 Torr)
several conditions available:
1.CeCl3/THF
sonication is better than stirring, 1 hr at rt is good enough.
grignard added into CeCl3 at -78C, then ketone.
2.CeCl3 with TiCl4
Even beta-ketone ester can be alkylated to the the beta-alcohol ester! Only successful when gama position is phenyl.
3.CeCl3.2xLiCl in THF
Friday, August 31, 2007
C-alkylation vs. O-alkylation
canion effect:
Li, Na, K, Cs
C---------O
smaller canion like Li can chelate with Oxygen, so carbon is more active compared to the oxygen atom. But at the same time, both C and O are less reactive compared to bigger canion!
solvent effect:
hexane, toluene, THF, acetone, DMF, DMSO
C----------------------O
substrate is less solvated in less polar solvent.
temperature
high temp seems favor O alkylation.
leaving group
OTs, Br, I
soft leaving group favors C-alkylation.
Li, Na, K, Cs
C---------O
smaller canion like Li can chelate with Oxygen, so carbon is more active compared to the oxygen atom. But at the same time, both C and O are less reactive compared to bigger canion!
solvent effect:
hexane, toluene, THF, acetone, DMF, DMSO
C----------------------O
substrate is less solvated in less polar solvent.
temperature
high temp seems favor O alkylation.
leaving group
OTs, Br, I
soft leaving group favors C-alkylation.
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