Reactions of Nucleophiles with Electrophiles Bound to Carbohydrate Auxiliaries - Carbohydrates: Tools for Stereoselective Synthesis - page 18

1.6
Addition of Phosphites

Vasella and coworkers first reported the stereoselective synthesis of
α

-aminophosphonic acids by means of carbohydrate auxiliaries [39, 40]. In the first
experiments N -mannofuranosylnitrones 87 (R i Pr, CH 2 OBn, Me) were reacted

with lithium dialkyl phosphites, affording the corresponding

=

-aminophosphonic
acids with up to 90% de [39]. In a second approach, which was amenable to a wider
range of N -mannosylnitrones 87, tris(trimethylsilyl)phosphite ( 88 ) was employed
under acid catalysis with HClO 4 , giving (R) - N -hydroxyphenylphosphaglycines 90
in high yield and with an optical purity of 88% after acidic work-up. Hydrogenoly-
sis of 90 gives (R) -phenylphosphaglycines 91, with optical purities of up to 88%
(Scheme 1.27) [40].

α

O
O O O

O
O

O

O

O O

P(OSiMe 3 ) 3
HClO 4
CH 2 Cl 2 , -70 °C

88

O

P(OSiMe 3 ) 2

N

Me 3 SiO

H

+

N

C

- O

R

R

87 89

O O

HOHN P(OH) 2 H 2 N P(OH) 2

1M HCl
MeOH

H 2 , Pd/C
0.5M HCl MeOH

R R

91

90

Scheme 1.27 Synthesis of (R) -phenylphosphaglycine 91 using a mannose-derived carbohy-
drate auxiliary.

In 1992 Kunz and coworkers reported the stereoselective synthesis of

α -aminophosphonic acid derivatives from O -pivaloylated galactosylamine as chiral

auxiliary [41]. The galactosyl amine 3 was reacted with various aldehydes to give
N -galactosyl aldimines 5, which were reacted with diethyl phosphite to furnish the
four diastereomeric N -galactosylphenyl phosphonoglycine esters 92 in high yield
by catalysis with tin(IV) chloride in THF (Scheme 1.28). The new stereocenter in
esters 92 was preferentially obtained in (S)- configuration, and the anomeric
configuration was predominantly β , except for the cases with R = 2-MeOC 6 H 4 and

R -anomers were found.

The (R) -configured aminophosphonic acids can be obtained by employing the
l-fucose-derived Schiff base 93 as a pseudo enantiomeric auxiliary [41]. The dias-
tereomeric mixture of the addition products 94 was treated with 1M hydrogen
chloride in methanol at room temperature, giving the carbohydrate template and
the

= Pr, where substantial amounts of the α

α -aminobenzylphosphonate hydrochloride 96 in quantitative yield (Scheme

1.29).
Miao has also reported the diastereospecific formation of

-aminophosphonic
acids derivatives in high yield via a Mannich-type reaction [42]. The reaction was

α