DOMINO REACTIONS IN THE ENANTIOSELECTIVE SYNTHESIS OF BIOACTIVE NATURAL PRODUCTS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 302

H [Sn]

[Sn]

[Sn]

BnON CO 2 Et

BnON CO 2 Et

Bu 3 SnH, AIBN
Benzene
45%

BnON CO 2 Et

MeO 2 C

MeO 2 C MeO 2 C

N

N N

O

O O

271 272 273

HN

O

O

HN

BnO

N

HN

N

HO 2 C

MeO 2 C MeO 2 C

steps

N
H N N

N

O

O

NH

275 274

NH

Martinellic acid 276

SCHEME 9.46 Synthesis of martinellic acid 276 by Naito and coworkers.

carbamyl radical 266 , which then underwent a 5- exo - trig cyclization to afford oxaz-

olidinone 267 . Fragmentation of the pinene moiety to the more stable radical 268 and

workup produced oxazolidinone in a stereoselective manner. This compound was

then taken through to the natural product

269

following initial hydrolysis of the
oxazolidinone moiety to the corresponding amino alcohol.
The pyrroloquinoline natural product (

270

), isolated from
the root bark of Martinella iquitosensis , was targeted by Naito and coworkers by
means of a domino-based approach [105]. Compound

)-martinellic acid ( 276

, which exhibits antibac-
terial activity, was also found to be a bradykinin receptor antagonist. In the key
radical-based domino reaction, the enantiopure oxime ether

276

271 was treated with

275

tributyltin hydride and AIBN to afford tetracyclic (45%) and small amounts of

three diastereomers (Scheme 9.46). In this so-called radical addition/cyclization/
elimination (RACE) reaction, the initial formation of the stable benzyl radical species
272 is projected. An intramolecular cyclization of the aforementioned radical with

the adjacent a , b -unsaturated ester then provides intermediate 273 , which then
undergoes a second cyclization to form the upper lactam within compound 274 .
The final step, an elimination of benzyl alcohol, furnished

in 45%yield alongwith
small amount of the three corresponding diastereomers (Scheme 9.46).
The vine Tripterygium wilfordii has been used in Chinese medicine for a
range of disorders for centuries and also contains compounds with antileukemic
properties, such as triptolide and tripdiolide [106]. In addition, (

275

),
a ring terpenoid, has also been isolated from this natural source. This tricyclic
compound was targeted by Yang and coworkers through a diastereoselective domino
radical cyclization involving an ( R )-pulegone-based chiral ester as the chiral auxiliary
(Scheme 9.47) [107]. Hence, when this compoundwas treatedwithMn(OAc) 3 andYb
(OTf) 3 , the tricyclic

þ )-triptocallol ( 279

278 was produced through a twofold ring closure in 60% yield