Chemistry Reference
In-Depth Information
tum and a stirrer bar was placed a solution of (1S,2R)-N-[2-(tert-butyldimethylsil-
oxy)-1-methyl-2-phenylethyl] formamide 1592 (15.3 g, 52 mmol) in freshly distilled
dichloromethane (100 mL). At 0
C, while stirring under nitrogen, the solution was
treated with POCl
3
(4.86 mL, 52 mmol) and triethylamine (22 mL, 158 mmol, 3.04
mol equiv.) by means of a syringe. The mixture was stirred for 5 min, and then
filtered through silica gel. The silica gel was rinsed with several portions of diethyl
ether. The combined filtrate and washings were concentrated under reduced pres-
sure and the residue was purified by flash column chromatography (diethyl ether/
hexane, 1:9, v/v). Evaporation of the solvents gave (1S,2R)-2-(tert-butyldimethyl-
siloxy)-1-methyl-2-phenylethyl isocyanide 1593 as a pale-yellow oil (9.7 g, 68%); MS:
m/z
ΒΌ
218.1008.
1590
1591
1594
Se
H
NH
2
TBDMSO
NH
2
TBDMSO
N=C=Se
H
O
N
TBDMS-Cl
Ph
Ph
TBAF
Ph
Ph
HCO
2
H
Se
64 %
1595
TBDMSO
NHCHO
TBDMSO
NC
POCl
3
Et
3
N
CH
2
Cl
2
Ph
Ph
70 %
1593
1592
Trioxazolo[2]metacyclophane 1599 can be obtained by a smart synthesis from a
cyclization reaction of 1-(3
0
-formylphenyl)-1-(4
0
-toluenesulfonyl)-methylisocyanide
1598 (3-formylphenyl-TosMIC). 1598 is obtained in 53% yield by dehydration of the
corresponding formamide 1597 with phosphoryl chloride [1200].
Tos
Tos
O
N
CHO
NHCHO
NC
TosNa
N
O
POC
l
3
EtONa
HCONH
2
Et
3
N
CHO
CHO
CHO
53 %
1598
1596
1597
63 %
1599
O
N
The above synthesis gives an example of the high synthetic value of 1-substituted
TosMICs (p-toluenesulfonyl methylisocyanides). TosMIC 1600 has been created by
van Leusen, who describes syntheses of some chiral sulfonylmethyl isocyanides as
TosMIC analogues [1201]. Most of the isocyanides 1600-1605 are prepared by
dehydration of the corresponding formamides with phosphoryl chloride, whereby
yields of 60-85% are obtained. The chiral isocyanides are compared in terms
of their ability to achieve asymmetric induction in base-mediated reactions with
