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

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.