Chemistry Reference
In-Depth Information
Typical procedure. a-Tosylbenzyl isocyanide 1616 [1205]:
A 1-L, three-necked, round-
bottomed flask fitted with an overhead stirrer, a 100 mL addition funnel, and a
temperature probe was charged with THF (200 mL) and 1615 (27.6 g, 94.8 mmol).
Phosphoryl chloride (17.7 mL, 190 mmol) was added and the resulting solution
was stirred for 5 min at 25
C. After cooling the solution to 0
C, triethylamine
(79.3 mL, 569 mmol) was added slowly over 30-45 min while keeping the internal
reaction temperature below 10
C. After the addition of triethylamine was com-
plete, the reaction mixture was warmed to 5-10
C and maintained at this tem-
perature for 30-45 min. Ethyl acetate (140 mL) and water (140 mL) were added
sequentially to the reaction mixture, stirring was continued for 5 min, and then the
mixture was transferred to a separatory funnel and the aqueous layer was removed.
The organic layer was washed with water (2
140 mL), saturated sodium hydro-
gen carbonate solution (140 mL), and brine (70 mL). The organic layer was trans-
ferred to a 500-mL, round-bottomed flask and concentrated on a rotary evaporator.
The residue was diluted with 1-propanol (140 mL) and this solution was con-
centrated on a rotary evaporator to half of its original volume. The residue was
cooled to 5-10
C for 30 min and the beige solid that crystallized was collected by
filtration through a B¨chner funnel. The filter cake was rinsed with 1-propanol
(2
75 mL). The beige solid was dried in vacuo for 3-4 h to give 18.1-19.7 g (70-
76%) of a-tosylbenzyl isocyanide 1616.
Structurally analogous to TosMIC 1600 is PhosMIC 1617, which has a phospho-
nate residue instead of a sulfonate residue. Some representatives have been de-
scribed by Bartlett [1206].
NC
O
P
O
NC
P
Ph
P
NC
Ph
O
EtO
O
O
O
EtO
O
PhosMIC
1617
1618
1619
Van Leusen [1207] has introduced chiral isocyanomethylphosphonates into this
field. Both cis-2-(isocyanomethyl)-5,5-dimethyl-2-oxo-4-phenyl-1,3,2-dioxaphosphor-
inane 1618 and the trans epimer 1619 have been prepared as potentially useful
chiral isocyanomethylphosphonate synthons.
Typical
)-cis-2-(Isocyanomethyl)-5,5-dimethyl-2-oxo-4-phenyl-1,3,2-dioxa-
phosphorinane 1618 [1207]: A solution of POCl
3
(2.4 mL, 26.0 mmol) in di-
chloromethane (10 mL) was added dropwise to a stirred solution of (
G
)-cis-2-
(formamidomethyl)-5,5-dimethyl-2-oxo-4-phenyl-1,3,2-dioxaphosphorinane (6.38 g,
22.5 mmol) and iPr
2
NH (9.5 mL, 67.5 mmol) in dichloromethane (130 mL) at
procedure.
(
G
20
C and the reaction mixture was stirred for 2.5 h at 0
C. Aqueous NaHCO
3
(20 g in 150 mL of water) was added carefully (evolution of CO
2
) and the mixture
was stirred for 20 min. The layers were separated and the aqueous layer was ex-
tracted with dichloromethane (3
30 mL). The combined organic layers were dried
