Highly enantioselective addition of diethylzinc to N-diphenylphosphinylimines using dendritic chiral ligands with hydrocarbon backbones

Article abstract of DOI:10.1016/S0957-4166(00)00194-4

Chiral dendrimers bearing three or six chiral β-amino alcohols on the hyperbranched hydrocarbon chain-ends act as efficient chiral ligands for the enantioselective addition of diethylzinc to N-diphenylphosphinylimines to afford enantiomerically enriched N

Full text of DOI:10.1016/S0957-4166(00)00194-4

Tetrahedron: Asymmetry 11 (2000) 2271±2275
Highly enantioselective addition of diethylzinc to
N-diphenylphosphinylimines using dendritic chiral ligands
with hydrocarbon backbones
Itaru Sato, Ryo Kodaka, Takanori Shibata, Yutaka Hirokawa, Nobuaki Shirai,
Koji Ohtake and Kenso Soai*
Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka, Shinjuku-ku, Tokyo,
162-8601 Japan
Received 27 April 2000; accepted 12 May 2000
Abstract
Chiral dendrimers bearing three or six chiral b-amino alcohols on the hyperbranched hydrocarbon
chain-ends act as ecient chiral ligands for the enantioselective addition of diethylzinc to N-diphenyl-
phosphinylimines to a€ord enantiomerically enriched N-diphenylphosphinylamines with up to 94% e.e.
# 2000 Elsevier Science Ltd. All rights reserved.
Dendrimer, an orderly hyperbranched macromolecule, is de®ned as one of the polymers with a
certain molecular weight and a molecular architecture. Its characteristics are usually determined
by the functional groups at the chain-ends.1 3 When the well-designed chiral functionalities are
loaded on the chain-ends of the dendritic backbone, those functionalities are positioned on the
surface and the resulting chiral dendrimer is expected to act as a chiral ligand in asymmetric
synthesis. Dendritic chiral ligands are prominent in their features among other polymeric chiral
ligands4 such as: (1) all of the chiral sites are placed on the surface of a dendrimer; and (2)
individual chiral environments of these functionalities are approximately the same, while those of
the chiral functionalities on other polymers are not. However, dendrimers modi®ed by chiral
functionalities at the terminal positions have rarely been utilized in asymmetric synthesis.5 7 Our
recent report shows that the dendrimers loaded with chiral amino alcohols on hydrocarbon
backbones can be used as e€ective chiral ligands in the enantioselective alkylation of aldehydes.8
Meanwhile, the enantioselective alkylation of imines represents one of the challenges in
asymmetric synthesis.9 Compared with the asymmetric addition of dialkylzincs to aldehydes,10 an
enantioselective addition of dialkylzincs to imines has rarely been examined. We previously
reported the enantioselective alkylation of N-diphenylphosphinylimines in the presence of chiral
* Corresponding author. Tel: +81-3-3260-4271; fax: +81-3-3235-2214; e-mail: ksoai@ch.kagu.sut.ac.jp
0957-4166/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00194-4

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b-amino alcohols which provides a direct and convenient method for the formation of enantio-
merically enriched secondary N-diphenylphosphinylamines.11,12 Subsequent removal of the
diphenylphosphinyl group by acid hydrolysis a€ords enantiomerically enriched secondary
amines.13
We report here a highly enantioselective addition of diethylzinc (Et2Zn) to N-diphenyl-
phosphinylimines in the presence of dendritic chiral ligands possessing hydrocarbon backbones.
Each of chiral ligands 1a and 1b bears three chiral sites on the para- and meta-positions to the
backbone, respectively, and a second-generation chiral ligand 2 possesses six chiral b-amino
alcohols on the phenylacetylene chain-end (Fig. 1).
Figure 1.
ꢀ1†
N-Diphenylphosphinylimines were treated with Et2Zn in the presence of dendritic chiral
ligands 1a,8 1b,14 and 28 (Eq. (1)). All the reactions were carried out in toluene at room
temperature. The results are summarized in Table 1. In the presence of para-substituted chiral
ligand 1a (0.34 mol equiv.), N-diphenylphosphinylimine 3a was ethylated to give N-diphenyl-
phosphinylamine (R)-4a with 89% e.e. (Entry 1).15 Enantioselective alkylations of N-diphenyl-
phosphinylimines 3b and 3c in the presence of chiral ligand 1a gave the corresponding chiral (R)-
amines 4b and 4c with 94 and 89% e.e., respectively (Entries 2 and 3). N-Diphenylphosphinylimine

I. Sato et al. / Tetrahedron: Asymmetry 11 (2000) 2271±2275
2273
3d with heteroaromatic ring was also ethylated to a€ord enantiomerically enriched (R)-4d (Entry
4). On the other hand, meta-substituted chiral dendrimer 1b drove asymmetric ethylation of N-
diphenylphosphinylimines with 73 to 85% e.e. (Entries 5±7). The enantioselectivity of chiral
ligand 1a was higher than that of 1b. This is probably due to the fact that the environments of
active sites of 1a have enough space to work as a chiral ligand, while active sites of 1b are too
close to the backbone chains. Highly enantioselective ethylation also proceeded using dendritic
chiral ligand 2 bearing six amino alcohols. In the presence of 0.17 mol equiv. of 2, imine 3a was
converted to (R)-amine 4a with 87% e.e. in good yield (Entry 8). The reaction was complete
within 20 h. The rate of the reaction was almost the same as in the cases using 0.34 mol equiv. of
dendritic ligand 1a (Entry 1) or 1.0 mol equiv. of N-benzylephedrine.15 The ligand 2 could be
recovered (80%) by puri®cation on silica gel TLC (Entry 8) and could be reused without a
considerable change in the enantioselectivity (81% e.e.). Similarly, enantioselective addition of
Et2Zn to imines 3b and 3c gave amines 4b and 4c in 90 and 85% e.e., respectively (Entries 9 and
10).
Table 1
Enantioselective alkylation of various N-diphenylphosphinylimines 3a±d using dendritic chiral ligands 1a,b and 2
Typical experimental procedure is as follows (Table 1, Entry 9): To a solution of N-diphenyl-
phosphinylimine 3b (63.9 mg, 0.20 mmol) and dendritic chiral ligand 2 (68.2 mg, 0.033 mmol) in
toluene (4 ml) was added a 1 M toluene solution of Et2Zn (0.6 ml, 0.6 mmol) at 0ꢁC under an
argon atmosphere. After the mixture was stirred at room temperature for 20 h, saturated aq.
ammonium chloride (5 ml) was added. The mixture was ®ltered using Celite, and the ®ltrate was
extracted with dichloromethane. The combined organic layer was dried over anhydrous sodium
sulfate and evaporated. Puri®cation of the residue by silica gel TLC (developing solvent,
hexane:ethyl acetate:methanol=5:4:1) gave N-diphenylphosphinylamine (R)-4b (51.1 mg, 79%).
Enantiomeric excess was determined as 90% by HPLC analysis using a chiral stationary phase
(Chiralcel OD).

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I. Sato et al. / Tetrahedron: Asymmetry 11 (2000) 2271±2275
In conclusion, chiral dendrimers bearing three or six b-amino alcohols on the hyperbranched
hydrocarbon chain-ends work as ecient chiral ligands for the enantioselective addition of
diethylzinc to N-diphenylphosphinylimines. The corresponding N-diphenylphosphinylamines are
obtained with up to 94% e.e.
Acknowledgements
This work was supported by a Grant-in-Aid for Scienti®c Reseach from the Ministry of Edu-
cation, Science, Sports and Culture. I.S. is grateful for a Daicel Award in Synthetic Organic
Chemistry.
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24
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D
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