AMMONIUM YLIDES AS BUILDING BLOCKS FOR ALKALOID SYNTHESIS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 473

O

H

H

Cu(acac) 2

O

O

N 2

N

N

N PhH, reflux 65%

374 375 376

O

O

O

Cu(acac) 2

N

N

PhH, reflux

N 2 N

24%

377 378 379

N 2

O

N

Cu(acac) 2

N

O

N

56%

PhH, reflux

H

O

380 381 382

SCHEME 13.70

to provide expected [2,3]-rearrangement products when heated with ethyl diazoa-
cetate and Cu(acac) 2 ; rather, the aziridine ring opens to give 1,3-dipole 384
(Scheme 13.71). Simultaneous decomposition of the diazo ester produced diethyl
fumarate that underwent cycloaddition with 384 to provide 385 in 49% yield.
Intramolecular reactions, however, did provide the expected products, though in low
yields. Thus, heating 386 with catalytic amounts of Cu(acac) 2 in acetonitrile produced
388 in 21% yield. The low yield, similar to that observed by Clark and coworkers for
377 , was explained in terms of the configurational dynamics of the aziridine that arise
from Walden inversion (cf. 346 versus 347 in Scheme 13.64). Analysis of NMR
spectra revealed that 386 exists as a 3:4 mixture of configurations 386a and 386b that
do not interconvert rapidly. While 386a can decompose to form 387 , it was suspected
that 386b undergoes a [1,5]-hydrogen shift faster than ylide formation. To support
this, aziridine 389 , which exists only in the configuration that cannot lead to [2,3]-
rearrangement, was subjected to the same reaction conditions and produced a mixture
of 390 and tautomer 391 in 64% yield via a [1,5]-hydrogen shift. That the diazo group
survives demonstrates that the [1,5]-shift is more facile than ylide formation.
The Aggarwal group developed an approach for generating an ammoniumylide
using the Simmon-Smith reagent [123]. Reaction of 392 with Zn(CH 2 I) 2 in ether
at 0 C for 2 days produced an ammonium salt that was remarkably stable
(Scheme 13.72). Subsequent reaction with n -BuLi at 30 C for 2 h gave exclusively
the [2,3]-rearrangement product 393 in 76% yield. This method was applied to the
stereospecific synthesis of an oxazocine. Oxazolidine 394 was treated with the
Simmons-Smith reagent followed by n -BuLi to give 396 in 72% yield and 398 in
5% yield, each as a single diastereomer. Again, the stereochemistry of the interme-
diate ylide is critical to the product distribution as 395 leads to 396 and 397 leads to
398 . Interestingly, the stereochemical course of the [1,2]-shift that forms 398 is
unexpected for the diradical mechanism that

typically occurs in the Stevens