Zhu et al.
JOCArticle
SCHEME 5. Proposed Process of CdN Alkynylation
It would be transformed to C by deprotonation of trimethyl-
silylacetylene.26 While substrate 1a was added, the oxygen
atom was coordinated with ZnA immediately. As the reaction
proceeds, the nitrogen of the substrate was coordinated with
the Lewis acid (ZnB, Scheme 5). At the same time, the
Michael-type transfer process occurred. When the addition
was finished, the -CdN-PdO disappeared and a new
-NdP bond formed.27 As a result of the disappearance of
both -CdN and -PdO, the nitrogen atom becomes more
electron-rich, and the nitrogen atom of-NdP might coordi-
nate with the Lewis acid (ZnB, Scheme 5) more strongly. So, it
is difficult for the pre-product to disengage from the ligand/
Zn species. That would nicely account for why a stoichio-
metric amount of ligand was employed for this addition.
were injected. The mixture was stirred for 30 min, and trimethyl-
silylacetylene (148 μL, 1.2 mmol, 6 equiv) was added. After an
additional 7 h of stirring, the substrate was added into the flask
at 0 °C. The reaction mixture was quenched with saturated
aqueous NH4Cl (2 mL) and extracted with CH2Cl2 (3 ꢀ 5 mL)
after stirring for 48 h. The combined organic layers were dried
over anhydrous Na2SO4. After filtration and evaporation of the
solvents, the crude residue was purified by flash chromatogra-
phy (silica gel, hexane/ethyl acetate), giving the corresponding
product.
P,P-Diphenyl-N-(1-phenyl-3-(trimethylsilyl)prop-2-ynyl)phos-
phinic Amide, 2a. White solid, mp = 141-143 °C, 72% yield.
90% ee determined by HPLC analysis (Daicel Chiralcel AD
column, hexane/isopropyl alcohol 95:5, 1.0 mL/min). Reten-
tion time: tmajor = 13.21 and tminor = 12.24 min. [R]20D = -21.5
(c 5.3, CHCl3). 1H NMR (300 MHz, CDCl3): δ 8.09-8.02
(m, 2H), 7.83-7.77 (m, 2H), 7.64 (d, J = 7.2 Hz, 2H), 7.55-7.43
(m, 4H), 7.40-7.27 (m, 5H), 5.19 (t, J = 10.2 Hz, 1H), 3.54
(t, J = 9.6 Hz, 1H), 0.20 (s, 9H). 13C NMR (75 MHz, CDCl3):
δ 140.0 (d, J(c-p) = 3.8 Hz), 133.5, 132.8 (d, J(c-p) = 9.8 Hz),
132.6, 132.0 (d, J(c-p) = 3 Hz), 131.9 (d, J(c-p) = 2.3 Hz), 131.7
(d, J(c-p) = 6 Hz), 131.6, 130.9, 128.5, 128.3, 127.8, 127.3, 104.9
(d, J(c-p) = 6 Hz), 90.1, 47.0. IR (KBr): ν 3394, 3062, 2961,
2252, 1439, 1250, 1195, 1125, 908, 734 cm-1. HRMS calcd for
C24H26NOPSi þ Hþ: 404.1594; found 404.1592.
Conclusion
In conclusion, we have designed and synthesized C2- and
C3-symmetric chiral proline-derived β-amine alcohol li-
gands, which have been successfully applied to the enantio-
selective nucleophilic addition of trimethylsilylacetylene to
N-phosphinoylimines. Aromatic, heteroaromatic, and ali-
phatic N-(diphenylphosphinoyl) imines and several
N-(diethoxyphosphoryl) imines were tested and produced
the corresponding propargyl amines with good yields (up to
92%) and excellent enantioselectivities (up to 95%) at room
temperature. Furthermore, the Michael-type addition pro-
cess of CdN alkynylation was studied, and a mechanism was
proposed on the basis of React 31P NMR investigation.
Representative Procedure for the Deprotection of Trimethyl-
silyl of P,P-Diphenyl-N-(1-phenyl-3-(trimethylsilyl)prop-2-ynyl)-
phosphinic Amide. P,P-Diphenyl-N-(1-phenyl-3-(trimethyl-
silyl)prop-2-ynyl) phosphinic amide (40.3 mg, 0.1 mmol) was
dissolved in dry THF (0.5 mL) and cooled to 0 °C, and Bu4NF
(0.03 mL, 0.03 mmol, 1 M in THF) was added dropwise. The
mixture was stirred at 0 °C for 15 min. Water (2 mL) was added
and extracted with diethyl ether (3 ꢀ 2.5 mL). The combined
organic fraction was dried over Na2SO4, filtered, and con-
centrated in vacuo. The crude product was purified by column
chromatography on silica gel.
Experimental Section
Representative Procedure for the Asymmetric Alkynylation of
N-Benzylidene-P,P-diphenylphosphinic Amide. Under an argon
atmosphere, into an oven-dried Schlenk flask was placed L4
(34.8 mg, 0.12 mmol), and anhydrous toluene (1 mL) and a
solution of diethylzinc in toluene (0.8 mL, 0.8 mmol, 4 equiv)
P,P-Diphenyl-N-(1-phenylprop-2-ynyl)phosphinic Amide, 3a.
White solid, mp = 152-155 °C, 87% yield. 1H NMR (300 MHz,
CDCl3): δ 8.07-8.00 (m, 2H), 7.90-7.83 (m, 3H), 7.63 (s, 1H),
7.60 (s, 1H), 7.55-7.26 (m, 9H); 13C NMR (75 MHz, CDCl3):
δ 132.6 (d, J(c-p) = 9.8 Hz), 132.1 (d, J(c-p) = 7.5 Hz), 128.7
(d, J(c-p) = 3.5 Hz), 128.5, 128.1, 127.1, 73.7, 46.5. IR (KBr):
ν 3372, 3296, 2923, 2979, 2854, 1956, 1734, 1654, 1439, 1383,
1189, 1118, 1066, 1028, 697, 546 cm-1. HRMS calcd for
C21H18NOP þ Hþ: 332.1199; found 332.1193.
(26) Modern Acetylene Chemistry; Stang, P. J., Diederich, F., Eds.; VCH:
Weinheim, 1995.
(27) For similar reports about the Michael addition process, see: (a)
Michael, A. J. J. Prakt. Chem. 1987, 35, 349. (b) Hunt, D. A. Org, Prep.
Proced. Int. 1989, 21, 705. (c) Hoz, S. Acc. Chem. Res. 1993, 26, 69. (c) Ihara,
M.; Fukumoto, K. Angew. Chem., Int. Ed. 1993, 32, 1010. (d) Itoh, T.;
Shiramaki, S. Heterocycles 2001, 55, 37. (e) Cai, C.; Soloshonok, V. A.;
Hruby, V. J. J. Org. Chem. 2001, 66, 1339. (f) Bolm, C.; Kanyan, A.; Heider,
P.; Saladin, S.; Drauz, K.; Gunther, K.; Wagner, C. Org. Lett. 2002, 4, 2265.
Representative Procedure for the Hydrogenation of P,P-
Diphenyl-N-(1-phenylprop-2-ynyl)phosphinic Amide. P,P-Di-
phenyl-N-(1-phenylprop-2-ynyl)phosphinic amide (33.1 mg,
6984 J. Org. Chem. Vol. 74, No. 18, 2009