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: