Chemistry Reference
In-Depth Information
Typical procedure. (17-Tetrabenzo[a,c,g,i]fluorenyl)methyl chloroformate 101 [57]:
Tet-
rabenzo[a,c,g,i ]fluorenyl-17-methanol (1.0 g, 2.52 mmol) was taken up in dichloro-
methane (20 mL) along with triphosgene (0.5 g, 1.68 mmol), and N,N-dimethyla-
niline (DMA) (0.64 mL, 5.04 mmol) was added. The mixture was stirred for 45 min
and the precipitated solid was filtered off and recrystallized from dichloromethane/
n-hexane to give (17-tetrabenzo[a,c,g,i]fluorenyl)methyl chloroformate 101 as a pale-
yellow solid (0.577 g). A further crop of the product was obtained from the di-
chloromethane filtrate after adding water, acidifying to pH 1 with 2 m HCl, drying
the organic layer (MgSO
4
), removing the solvent, and recrystallizing the residue
from dichloromethane/n-hexane. Total yield (0.819 g, 71%).
2,2-Dichlorovinyl chloroformate 104, a stable and active acylating agent (e.g. for the
protection of alcohols in acidic media) was prepared for the first time from 1,2,2,2-
tetrachloroethyl chloroformate 103 (an a-chloroalkyl chloroformate synthesized by
treatment of chloral 102 with phosgene in the presence of a reusable ''naked Cl
''
catalyst) by dehalogenation with Zn dust [58].
O
Cl
Cl
Cl
COCl
2
Zn
Cl
Cl
O
l
O
l
H
Cl
Cl
THF
Cl
Cl
O
O
65 %
75 %
102
103
104
Typical procedure. 1,2,2,2-Tetrachloroethyl chloroformate 103 [58]:
Freshly distilled
chloral (4.4 g, 0.030 mol) was added (over 30 min) to a stirred refluxing solution
(dry-ice Dewar condenser) of benzyl tri-n-butylammonium chloride (BTBAC) (10 g,
0.032 mol) in phosgene (for a safe source, see Chapter 7) (60 mL). After 1 h, the
excess phosgene was removed through a series of five bubble traps (empty, H
2
SO
4
,
empty, aqueous NaOH, NH
4
OH to hood exhaust) with the aid of an aspirator, and
the 1,2,2,2-tetrachloroethyl chloroformate was isolated by distillation: bp 76-79
C/19
Torr, 47.7 g (65% yield). Note: Unless 1,2,2,2-tetrachloroethyl chloroformate is com-
pletely free from the catalyst, it slowly reverts to the reactants.
3-Benzyloxypropyl chloroformate 106, a useful reagent in the total synthesis of di-
and tri-O-methyl Dynemicin A methyl esters, was prepared by syringe pump addi-
tion (over 2 h) of 3-benzyloxypropanol 105 (2.9 equiv.) and pyridine (3.0 equiv.) to a
solution of triphosgene in dichloromethane at 0
C [59].
O
(CCl
3
O)
2
CO
O
O
Cl
O
OH
CH
2
Cl
2
, Py, 0°C
105
106
Triphosgene was used in the total synthesis of Calicheamicinone for the simultane-
ous activation of both a hydroxyl and amino group [60].
