Amidines in Organic Synthesis - Superbases for Organic Synthesis - page 56

N

R

I R

R

I 2

N

N N a : R = H (74%)

b : R = Me (71%)

N

acetone
reflux

EtO N

N N

R I

Scheme 3.11 Synthesis of cyclic amidines from imidate and aziridines

sulfonamide by treatment with -bromoorthobutanoate followed by azidation and reduc-

tion. These bisamidines are used as chiral ligands for the copper-catalysed enantioselective
Diels-Alder reaction [24a].
Bicyclic amidines are synthesized from aziridines and cyclic imidates [25]. Thus, NH-
aziridines react with cyclic imidates in the presence of a small amount of ammonium
bromide to give aziridinylamidine, which is treated with iodine (I 2 ) to give bicyclic
amidines. The use of 2-methylaziridine results in the introduction of methyl group at
position 2 of the bicyclic amidine product. The mechanism proposed is shown in
Scheme 3.11, which involves iodine-induced ring opening of aziridine and recyclization
of the resultant iodoethylamidine.

g

3.2.4.3 Haloiminium Salt
One-step conversion of N-( o -azidoalkyl)lactams to bicyclic amidines, avoiding the protec-
tion-deprotection sequence on the amine part, is explored by applying the intramolecular
Staudinger-type reaction [26]. Oxalyl chloride [(COCl) 2 ] and bromide [(COBr) 2 ] are found
to be effective trigger reagents and the corresponding bicyclic amidines are produced in high
yield (Table 3.1).
DBN (2) is prepared in 92% yield by treatment of N-(3-azidopropyl)-

-lactam with
oxalyl bromide after quenching with anisole (run 3). A trace of the reaction by IR spectrum
suggests the formation of a bromoiminium intermediate, which spontaneously cyclizes to
the bicyclic system through either 1,2-addition (path A) or [3

g

þ 2]cycloaddition (path B)

(Scheme 3.12).

Table 3.1 Synthesis of DBN (2) from N -(3-azidopropyl)- g -lactam

N 3

N

O

reagent

N

N

solvent

DBN ( 2 )

Run Reagent Solvent Yield (%)

1 Ph 3 PorBu 3 P xylene < 10

2 (COCl) 2 DCM 81

3 (COBr) 2 (CH 2 Cl) 2 92