preparation of 4-t-butyldiphenol

the following procedure seems to be the easiest.
from a chinese patent. application number:99124902

1. liquifiy pure diphenol by warming. no solvent needed.
2. add 1-5% TsOH-H2O.
3. keep temp at 135C, add 1 eq. MTBE dropwise in 2-3 hr (a cold condenser needed).
4. 1 hr later, you get the title compound with a yield >75%









note:
I tried the reaction, everything worked out as described.

a Convenient Procedures for Birch reduction

Turk J Chem
29 (2005) , 513 - 518.
http://journals.tubitak.gov.tr/chem/issues/kim-05-29-5/kim-29-5-7-0504-3.pdf

The reduction of aromatic rings by solutions of alkali metals in liquid ammonia was discovered by Wooster and Godfrey14, who reacted toluene with sodium in ammonia followed by the addition of water. They reported a "highly unsaturated liquid product", which was not identied further. However, the real development of this reaction was to follow in the work by Birch15. This reaction is generally referred to as the Birch reduction, although in some cases it is simply called metal-ammonia reduction. Wild and Nelson16 found adding alcohol last to be advantageous, as opposed to having it present when the metal is added, and it was subsequently discovered that it should be avoided altogether with polynuclear compounds.

Compared to the other reduction procedures of converting benzene and its derivatives to corresponding nonconjugated dienes, the new reduction procedures have certain advantages. These include the following:
1) These reduction reactions are carried out at room temperature, avoiding the low temperatures, under -33oC, needed to obtain liquid NH3.
2) The procedures are environmentally friendly30−34. Much more NH3 is needed when liquid NH3 is used as solvent. Evaporation of liquid NH3 may damage the environment.
3) Control of moisture is easier in our method, and the reaction may go on for longer periods. When the reaction is conducted with liquid ammonia, it may be quenched by the developing moisture.
4) Evaporation of liquid NH3 may take a long time and some side reactions such as isomerization and reoxidation may be observed. \
5) It is unnecessary for the researcher to observe the reaction carefully and continuously in the
present method because temperature control is not necessary, whereas the temperature must be checked in the reaction with liquid NH3.

Procedure 1: Reduction of benzene to 1,4-cyclohexadine.
In a 500-mL, 2-necked, round-bottomed flask tted with a reflux condenser and a stirring bar were placed tert-butanol (72 g, 0.963 mol, 2.85 equivalents), dry benzene (27.3 g, 0.35 mol, 1 equivalent) and dry THF (120 mL). The flask was attached to gas ammonia (NH3) whose pressure was approximately 1 atmosphere (atm) and the resulting solution was stirred. The reaction mixture was cooled in an icewater bath and then freshly cut lithium (7.35 g, 1.05 g-atom, 3 equivalents) was added over 3-5 min. The temperature of the bath was allowed to rise gradually to room temperature. After the addition of lithium was completed, the reaction mixture was stirred for 5 h. Two phases appeared in the reaction mixture.
The top and bottom phases were brown and gray, respectively. The mixture was cooled in an ice-water bath again. Cold water was added slowly and carefully to the flask until all the lithium was consumed, as evidenced by the conversion of the colors to white. The reaction mixture was poured into a mixture (250 g) of water and ice and was acidied with the addition of 2 N cold hydrochloric acid. The organic layer was separated and washed with cold water (100 mL), a solution of NaHCO3 (5%, 50 mL) and water (75 mL), in order that. The reduction product, 1,4-cyclohexadiene, was dried over CaCl2 and ltered. The yield (23.5 g) and conversion of the reaction were 84% and 100%, respectively.

Note:
checked this reaction by myself, it really works.

substrates scope:
obviously, product of entry 5 and 6 should be switched.

All-Up Reactive Conformation of Chiral Rhodium(II) Carboxylate Catalysts

by
Vincent N. G. Lindsay, Wei Lin, and Andre´ B. Charette*
doi: 10.1021/ja9044955

Chiral Rh(II)-carboxylate catalysts have found widespread use in the field of metal carbene transformations, including asymmetric cyclopropanation reactions.1 Though several enantioselective transformations have been developed to date, little evidence is known
on how the chirality is projected near the reaction center by the chiral carboxylates. Davies et al. have suggested that four main possible symmetries have to be considered, from which only two
possess equivalent catalyst faces (Figure 1, C2 and D2).2 It has been postulated that catalysts having two different carbene-formation sites should not be effective in inducing enantioselectivity, since the more kinetically active and accessible face is apparently achiral (C1 andC4).

However, Fox et al. recently contradicted this concept by reporting the highly efficient asymmetric cyclopropanation of alkenes with R-alkyl-R-diazoesters using such a catalyst, where DFT calculations demonstrated that the all-up conformation of the catalyst plays a prominent role in these reactions.

All our experiments suggest that the halogenated rhodium carboxylate catalysts used in this process react through an all-up conformation, which is consistent with Fox’s DFT calculations made on non-halogenated analogues.

C-3 arylation of indole

Challenging chemical architectures of natural origin often point to gaps in synthetic methodology. For instance, there is a shortage of methods for C-3 quaternization of indoles with an aryl appendage. A number of natural products including haplophytine,1 bipleiophylline,2 hodgkinsine,3 and leptosin D4 (Fig. 1) contain a quaternary indole C-3 with an aryl appendage or a structure theoretically derived from such a motif as with haplophytine.1h Recent efforts by Nicolaou and co-workers,5 and Fukuyama and coworkers6 in the context of haplophytine have demonstrated the feasibility of the synthetic union of a substituted indole C-3 with an
aryl nucleophile,6 or a pseudo-aryl electrophile,5 however, both approaches were highly substrate specific and proceed in less than 25% yield.
In a much simpler context, Barton and co-workers have shown that treatment of skatole with tert-butyl tetramethylguanidine (BTMG) in the presence of 1.5 equiv of Ph4BiOTs results in
95% conversion to the C-3 disubstituted indolenine 1 (Fig. 2).7 This approach suffers from the required use of 4 equiv of aryl donor for each aryl group transfer. Additionally, extensive studies in these laboratories have shown that this bismuth mediated protocol does not have broad substrate scope and requires a tedious five-step reagent preparation.8

Baran reaported this method:
Tetrahedron 65 (2009) 3149–3154

The strategy has been generalized and performs well with a wide variety of substrate and reagent combinations. While this strategy is somewhat limited with respect to efficiency in appending very electron rich arene rings to C-3 of indole substrates, other than highly substrate dependent cases of Nicolaou5 and Fukuyama,6 there are no comparable methods in the
literature that allow for the direct C-3 quaternization of indoles with an arene ring.

Scott Phillips, pen state university

Assistant Professor of Chemistry, Pennsylvania State University, 2008-

Research Fellow, George Whitesides Group, Harvard University, 2006-2008

Developed new materials and detection platforms with applications in
medicine, drug development, and less-industrialized nations.

Post-Doctoral Fellow, Matthew Shair Group, Harvard University, 2004-2006

Designed, synthesized, and analyzed the behavior of beta-strand and beta-sheet mimics.
Determined the energies associated with amino acid interactions in beta-sheets.
Developed chemical hosts to recognize peptide guests sequence-selectively in
water.

Education

Ph.D., University of California, Berkeley, 2004
boss Paul A. Bartlett

Designed, synthesized, and analyzed the behavior of beta-strand and beta-sheet mimics.
Determined the energies associated with amino acid interactions in beta-sheets.
Developed chemical hosts to recognize peptide guests sequence-selectively in
water.

B.S., California State University, San Bernardino, 1999

research area:

Chemistry for Resource-Limited Environments

We are using organic chemistry to create autonomous diagnostics--that is, diagnostic devices that provide all of the functions typically obtained with instruments i.e., (selectivity, sensitivity, quantitative measurements, and clearly displayed information), but using only organic reactions on a piece of paper. Our goal is to devise chemistry that forms the basis for exceedingly simple and disposable diagnostics devices. These systems will be useful in the developing world, emergency rooms, and other applications requiring portable and inexpensive devices for detecting disease or pollution. Projects in this area include: (i) Developing new reagents and strategies for signal and target amplification; (ii) developing new reactions for activity–based detection; and (iii) developing new strategies and new reagents for stabilizing biomolecules.

Designing Living Materials

We are developing materials that respond to external signals by changing shape, function, and/or surface properties. This work can be extended to developing materials that grow, and possibly divide. One aspect of this work includes the design and synthesis of environmentally–friendly plastics.

Unconventional Reaction Methodology

As the price of crude oil continues to rise, so too will prices of bulk chemicals derived from oil. We are developing reactions that use CO₂ as an inexpensive carbon source (in place of oil) for making bulk chemical building blocks.

A second program in this area focuses on reaction networks that are self-perpetuating, the simplest of which is an autocatalytic reaction (where a molecule makes more of itself). We plan to expand autocatalytic behavior into more complex reaction networks, with the goal of developing systems that provide useful function and/or byproducts.

Donald A. Watson, University of Delaware

Donald A. Watson was born in California in 1976. He received his BS in Chemistry from UC San Diego in 1998. During his undergraduate years, he worked in the laboratories of Professors K.C. Nicolaou and Emmanuel Theodorakis, working on natural products synthesis.

He completed his PhD in Organic Chemistry at UC Irvine in 2004, working under the direction of Professor Larry E. Overman. His dissertation work focused on stereochemical problems in palladium catalyzed transformations.

From 2004 to 2006 he was a NIH Postdoctoral Fellow in the laboratories of Professor Robert G. Bergman at UC Berkeley. During this time he developed zirconium-based catalysts for asymmetric intramolecular hydroaminations. He then moved to the Massachusetts Institute of Technology as to take a position as a Postdoctoral Associate in Professor Stephen L. Buchwald's laboratory, where he studied metal catalyzed processes C-F bond formation.

He joined the Chemistry and Biochemistry faculty at the University of Delaware as an Assistant Professor in July 2009.

1. Bimetallic Complexes for Remote Substrate-Directed Catalysis.

2.New Methods for the Preparation of a-Chiral Amines.

3. Electrocatalysts for the Reduction of CO2 to Methanol.

Publications:
pending

Bischler-Napieralski reaction

reagent: pocl3
solvent: mecn, benzene, toluene, dcm, dmpu.
temp: rt - reflux
time: several hours.

not a nice and clean reaction. usually low yielding because of the strong acidic condition.
the product imine is sometimes not stable.

some milder conditions:
1. pph3/ccl4/reflux
2. Tf2O

a nice link:

http://www.organic-chemistry.org/namedreactions/bischler-napieralski-reaction.shtm

Mary Watson, University of Delaware

Mary Waterson,
BS, 2000, Harvard University, phd, 2006 with Larry E. Overman, 2006–2009, postdoc with Eric N. Jacobsen. During her postdoc, she developed a nickel-catalyzed method for olefin arylcyanation via activation of C–CN bonds. She joined the faculty at the University of Delaware in July 2009.
Research:
centered on the discovery of new catalytic, stereoselective methods for organic synthesis by utilizing the power of both transition metal and Brønsted acid catalysts.
1. Selective Activation of Relatively Strong Bonds
C-H activation.
2. Brønsted Acid-Catalyzed Reactions of Unactivated Olefins
enantioselective additions of H–X (X = C, O, N, etc.) across olefins.

publication:
pending

A proposal of synthesis of maoecrystal V

In 2004, islolated was the maoecrystal V with a novel C19 skeleton from the leaves of a Chinese medicinal herb, Isodon eriocalyx. it is remarkably active against HeLa cells (IC50) 0.02 ug/mL).
The two chiral quaternary carbons and a tertiary alcohol in a contiguous setting served to pose interesting challenges to the science of chemical synthesis.
So far, no total synthesis. the following are just my thoughts.











another one. not better.










or umpolung chemistry.(sorry, one methyl is missing in the product).

what can you do if your precious compound spilled?

My precious compound spilled out of a bottle and sticked onto a piece of plastic foam. the foam was dissolved by the dcm which is the solvent with my compound.
Discard it ? no, the boss will kill me.

1 I cut the foam off and dissolved the foam (with my compound) with DCM/EtoAc.
The foam dissolved without problem. concentrated. passed a pad of silica gel, eluting with etoac, nothing can be removed.
2. checked the structure of the foam through internet, it is polystyrene,
http://en.wikipedia.org/wiki/Polystyrene
tried to run a TLC with pure polystyrene, no obvious spots.

3. tested the solubility of the foam in organic solvents.
soluble: dcm, etoac, ether
unsoluable: meoh, hexanes,
4. so meoh was added to precipitate the polystyrene, and a simple filtration with silica gel removed the plastic.

The radical reactions of imine radicals

Tetrahedron
Volume 65, Issue 36, 5 September 2009, Pages 7415-7421

In conclusion, imine radicals 5 and 15 can be generated from the manganese(III), silver(II) oxidation of 2-amino-1,4-benzoquinones. These free radical reactions provide efficient methods for the generation of the dimeric products 4 and 14. In the presence of styrene, twistane 17 was afforded from 2-phenylamino-1,4-benzoquinone 1 via a radical annulation reaction of imine radical 5.

mechanism:

Peptide–Dirhodium Ligation

Controlling Peptide Structure with Coordination Chemistry: Robust and
Reversible Peptide–Dirhodium Ligation
DOI: 10.1002/chem.200901266
Chem. Eur. J. 2009, 00, 0 – 0

interesting paper.

A novel iodine-mediated tandem cyclization

Chem. Commun., 2009DOI: 10.1039/b910232a

A novel iodine-catalyzed tandem cyclization–cycloaddition reaction of ortho-alkynyl-substituted benzaldehydes leading to polyoxacyclic ring systems has been developed, which represents a useful approach towards the synthesis of the oxabicyclo-[3.2.1]octane ring skeleton found in a variety of natural products.


mechanism:

Stereoelectronic Effect for the Selectivity in C−H Insertion of Alkylidene Carbenes

Stereoelectronic Effect for the Selectivity in C−H Insertion of Alkylidene Carbenes and Its Application to the Synthesis of Platensimycin

Sang Young Yun, Jun-Cheng Zheng and Daesung Lee* Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607-7061J. Am. Chem. Soc., 2009, 131 (24), pp 8413–8415DOI: 10.1021/ja903526g


High selectivity in the insertion between two competing C-H bonds was observed and is believed to be the manifestation of a strong stereoelectronic effect of oxygen substituents.

bromination with POBr3 POCl3

usual condition use Phosphorus(V) oxybromide or Phosphorus(V) oxychloride
in toluene, xylene and heat to over 120 C.
during the rxn, HBr/Br2 can be generated.
sometimes bring side reactions and low yields.

the following paper has a better procedure:
J. Chem. Soc., Perkin Trans. 1, 2002, 529–532

The use of phosphorus oxychloride to prepare compound 12 was sometime fraught with side reactions. Although a very efficient procedure has been recently reported,16 we developed a robust method, also using phosphorus oxychloride or bromide, but in the presence of potassium carbonate in boiling acetonitrile. Thus the troublesome hydrolysis of the reaction mixture takes
place under neutral conditions, without heat evolution, and avoids unwanted decomposition. The 1-halogenated derivatives 13 or 14 were thus routinely prepared in 82–85% yields.

Oxidation of Secondary Alcohols by Sodium Hydride ?

author:
Xinbo Wang, Bo Zhang and David Zhigang Wang

School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen, China 518055

J. Am. Chem. Soc., Article ASAP

DOI: 10.1021/ja904224y

Publication Date (Web): July 21, 2009


In this recent paper, a novel oxidation of Secondary Alcohols by Sodium Hydride was described.

. they said "Uncovered here are some unprecedented reactivities of this classical reagent under very mild conditions, including alcohol oxidation, tandem allylic alcohol oxidation−hydride conjugate reduction, and aldehyde oxidative amidation. These readily implementable transition-metal-free processes feature exceptional material accessibility, operational simplicity, and environmental compatibility."










very nice work.
while reading this paper, some thoughts popped out of my little brain.
Could it be some other metal species instead of NaH really catalized the rxn?

it is known that nah is a base, sometimes can be a hydride donor, but Na+ never seen as a hydride acceptor.
I guess there is something else which catalized the rxn.
1. although nah is catalyst and all recoved after rxn, they still need a huge amount.
2. nah is made from na metal, presence of trans metal such as Pd is very possible.
3. there is an example by a japanese group which found a heck coupling rxn without pd, but finally they said the base they used (t-buOK, K2CO3?) contains trace of pd which did the trick.
(can't really remember all the detail, sorry).

anyway, this is still a very useful rxn and I hope to see more detailed research on this topic which may answer my question.

news:23,07,2009
http://totallysynthetic.com/blog/?p=1903
They already found O2 is essential for the rxn to happen.

Haouamine biosynthesis ?

Baran found out biosynthesis of haouamine 1 via 4 is not possible .fig. 1, so turned down a proposed biosynthesis route by a french group. scheme 2.
here I propose a revised synthetic route a-[b]-c based on the biosynthesis scheme.
the reasoning is to make a bigger sized macro ring b first, then the center six membered ring should be accessable.

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).

Overmann synthesis of Actinophyllic Acid

Overman, Martin and Rohde. JACS, 2008, ASAP. DOI: 10.1021/ja803158y.

although it is racemic, it still went to jacs.
key step:

















aza-Cope Mannich.

some molecular accomplished by this method:

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

A proposal to make 7-Methylomuralide

Corey recently published the synthesis of (-)-7-Methylomuralide. very short synthesis. Here is my proposal. Also short, but racemic.

A way to make diazo compounds

From:
jac_2004_126_12222
Michael E. Furrow and Andrew G. Myers*


The bimolecular reaction of carboxylic acids with diazoalkanes
to form esters is among the mildest and most efficient of organic
transformations but is seldom used in synthesis beyond the
important case of methyl esterification.1 This is largely a consequence
of the inaccessibility and poor stability of higher diazoalkanes
as substrates.2 In this work we describe a new method for
the synthesis of diazoalkanes by the oxidation of N-tert-butyldimethylsilylhydrazones
(TBSHs) with (difluoroiodo)benzene,3 a reagent
heretofore unexplored in the context of hydrazone oxidation.
When conducted in the presence of a carboxylic acid substrate,
the oxidation leads to efficient esterification in situ (Scheme 1). In
addition to greatly extending the range of diazoalkanes that are
now available for esterifications, this new protocol offers significant
advantages with regard to safety, for diazo intermediates are neither
isolated nor achieve appreciable concentrations during the reaction.

deprotection/protection of allylether

1. formation of allyl ether.
allylbromide/base

2. deprotection.
1. pdcl2/acoh/Naoac/water. heated to 70C for 2 hr.
works ok, but sometimes cause decomposition of my sugar compound.
2. pd(PPh3)4/acoh, 80C. 2hr.
works great, high yield. rxn started even before heating at rt!

Swern oxidation typical procedure

Procedure: 25 mL 1-neck flask, stirbar, septum, N2 inlet

Dissolved 0.077 mL of oxalylchloride (II) in 4.0 mL of dry CH2Cl2. Stirred; cooled to -78 C. Added 0.125 mL of DMSO. Stirred 10 min. Added a solution of 0.096 g of alcohol I in 1.0 mL of CH2Cl2. Stirred 15 min. Added 0.250 mL Et3N. After 15 min, warmed to 0 C. After 10 min TLC showed complete reaction. The reaction mixture was placed on a silica gel column and the product was isolated by flash chromatography .

notes

1. temp is critical for high yielding.
2. other than oxalylchloride, many activator can be used to overcome problem caused by oxalylchloride (ex. Cl-), ex. P2O5.


cited from
http://www.alsnotebook.com/oxidswern.html

an approach to Actinophyllic Acid

This synthesis plan was made by me about half a year before Overmann's beautiful synthesis of the same molecular.

An approach to Sordaricin

This proposal is just another application of carbene chemistry in the total synthesis of natural products.

The armed–disarmed concept

The armed–disarmed concept refers to the relative ease
or difficulty of activating a sugar as a glycosyl donor in
glycosylation reactions.1 Disarmed glycosyl donors have
highly electron withdrawing protecting groups (e.g., esters,
amides) that destabilize the formation of the oxycarbenium
ion/ion pair2 during the course of the glycosylation,
whereas less electron withdrawing protecting groups (e.g.,
ethers) are less destabilizing and therefore arm the glycosyl
donor.

Tetrahedron Letters 49 (2008) 2546–2551

preparation of [Me2SSMe+][BF4-] (DMTSF)

what DMTSF can do?
electrophilic sulfenylation reagent capable of reacting with nucleophilic atoms;² reacts with electron-rich alkenes to promote addition reactions,³ cyclizations;⁴ activates dithioacetals,⁵ trithioorthoesters,⁶ and thioglycosides⁷ for carbon–carbon or carbon–heteroatom bond forming reactions). from e-EROS Encyclopedia of Reagents for Organic Synthesis.

Inorganic Chemistry, Vol. 42, No. 8, 2003
Following the published procedure,
solution containing 0.74 mL of methyl disulfide (8.06 mmol) in
7 mL of CH3CN was added dropwise to an equimolar amount of
Me3O+BF4- (1.04 g, 8.06 mmol) dissolved in 8 mL of CH3CN
at 0 °C. After the mixture had been stirred for 2 h at 0 °C, dry
ether was added to precipitate dimethylthiomethylsulfonium fluoroborate
([Me2SSMe+][BF4-]) as a white solid that was stored in
the glovebox at -36 °C (1.1 g; yield, 69%).

An example of protection of alkene by Diels-alder rxn

New approaches for the synthesis of erythrinan alkaloids

Org. Biomol. Chem., 2009, 7, 1963–1979

retro d-a reaction happened by heating in vacuum. 80% yield.

A synthetic proposal of calicheamicinone

This synthetic plan features a rhodium mediated cyclopropanation and a curtius rearrangement. the overall steps is about 16 which is almost half of the existing synthesis!
The biggest problem I can forsee is the stability of the enediyne before the cyclopropanation.

keyword: calicheamicin, calicheamicinone, retrosynthetic plan, proposal, synthesis

solvents for developing of TLC plates

1. The expected elution order of organic classes

alkanes
alkenes
ethers
halogenated hydrocarbons
aromatic hydrocarbons
aldehydes and ketones
esters
alcohols
amines
carboxylic acids

2. Eluting power of organic solvents

alkanes (hexanes, petroleum ether)
toluene
halogenated hydrocarbons (methylene chloride)
diethyl ether
ethyl acetate
acetone
alcohols
acetic acid

3. some useful combinations:

EtOAc in hexanes
MTBE in petroleum ether
EtOAc in benzene
MeOH in methylene chloride
acetone in methylene chloride

chiral building blocks - Others