1,2-Addition of Nucleophiles to Carbonyl Compounds - Carbohydrates: Tools for Stereoselective Synthesis - page 299

Table 13.4

Addition of phenylacetylene to aldehydes catalyzed by Zn(OTf) 2 / 14l-17l. a)

OH

O

Zn(OTf ) 2 , 11 l-14l

Ph R

RH +

Toluene, Et 3 N, rt

Ph

ee's up to 99%

O

N

O O

O

O

Ph Ph Ph O

Ph

O O O

O

O

OMe

HO HO

HO

N N

N

OMe

HO OMe OMe

O

O

14l 15l 16l

O

17l

D- α -gluco D- β -gluco D- α -allo

D- α -manno

Entry R Ligand Yield

(%)

ee (%)
(configuration)

Entry R Ligand Yield

(%)

ee (%)
(configuration)

1 Cy 14l 95 97 (R) 6 c- Pr 15l 71 94 (R)

2 Cy 15l 94 99 (R) 7 t- Bu 15l 62 97 (R)

3 Cy 16l 92 22 (R) 8 Ph(CH 2 ) 2 15l 15 98 (R)

4 Cy 17l 8 35 (R) 9 p- MePh 15l 38 97 (R)

5 i- Pr 15l 70 97 (R) 10 p- ClPh 15l 36 98 (R)

a) Conditions: ratio Zn(OTf) 2 /ligand/Et 3 N/acetylene/aldehyde = 1.1 : 1.2 : 1.2 : 1.2 : 1.0, toluene, 40 °C.

Since remarkable results in the addition of acetylenes to aldehydes were obtained
using carbohydrate-derived aminoalcohols, the library of ligands 14-17 (see
Scheme 13.6) was also assayed in this reaction (Table 13.4) [24]. Ligands 14c,e,j,k,l
and 14l-17l were selected for this screening. It was observed that cyclic amine
substituents at C2 ( 15l-17l ) gave enantioselectivities and yields higher than those
of acyclic ones, and α - ( 14l ) and in particular β -gluco ligands ( 15l ) gave selectivities

higher than those of -manno derivatives (entries 1-4, Table 13.4). Thus,

the addition of phenylacetylene to different aldehydes in the presence of Zn(OTf) 2
afforded excellent ee values, between 94% and 99%, when ligand 15l was employed
(entries 5-10, Table 13.4).
Finally, other acetylenes such as 4-phenylbut-1-yne, 2-methylbut-3-yn-2-ol, but-
3-yn-1-ol, and (triethylsilyl)acetylene were also successfully added to cyclohexylcar-
baldehyde using the catalytic system Zn(OTf) 2 / 15l (Table 13.5).
Since the first report by Li [25] on the asymmetric addition of alkynes to imines
[5] catalyzed by a Cu(I)/pybox catalytic system, this transformation has attracted
the interest of researchers due to the synthetic applications of the propargylamines
obtained.
The ligand gluco Pybox ( 50 ) [26], which is related to traditional pybox ligands
and incorporates two glucose units, was recently prepared from glucosamine

α -allo or α