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. Author manuscript; available in PMC: 2010 Aug 3.
Published in final edited form as: Chemistry. 2009 Jul 13;15(28):6910–6919. doi: 10.1002/chem.200900794

Table 5.

Cascade AAA for the synthesis of piperazinone 19[a]

graphic file with name nihms222469u2.jpg
Entry Pd source (mol %) Ligand (mol %) Additive (mol %) Temp. (°C) Yield (%)[b] Ee (%)[c]
1 [Pd(π-C3H5)Cl]2 (2) (R,R)-LST (6) LiHMDS (100) rt 0 NA
2 [Pd(π-C3H5)Cl]2 (2) (R,R)-LST (6) LiHMDS (200) rt 0 NA
3 [Pd(π-C3H5)Cl]2 (2) (R,R)-LST (6) none rt trace NA
4 [Pd(π-C3H5)Cl]2 (2) (R,R)-LST (6) Cs2CO3 (100) rt 0 NA
5 [Pd(π-C3H5)Cl]2 (5) (R,R)-LST (15) HOAc (10) rt trace [d] NA
6 Pd2(dba)3·CHCl3 (5) (R,R)-LST (15) HOAc (10) rt 51 NA
7 Pd2(dba)3·CHCl3 (5) (R,R)-LST (15) BSA (100) rt 50 NA
8 Pd2(dba)3·CHCl3 (5) (R,R)-LST (15) HOAc (10) 0 to rt 65[e] 89
9 Pd2(dba)3·CHCl3 (5) Rac-LST (15) HOAc (10) rt 88[e] NA
10 Pd2(dba)3·CHCl3 (5) (R,R)-LST (15) HOAc (10) 0 to rt 80[e,f] 96
11 Pd2(dba)3·CHCl3 (5) (R,R)-LST (15) HOAc (10) 0 to rt 82[e,g] 97.5
[a]

Unless otherwise indicated, all reactions were performed with 1.0 equiv of 8 and 1.0 equiv of 17 at 0.2 M in DCM.

[b]

Isolated yield.

[c]

Enantioselectivities were determined by chiral HPLC.

[d]

Single alkylation product was the main product.

[e]

The reaction was performed with 1.5 equiv of 8 and 1.0 equiv of 17.

[f]

Another portion of Pd2(dba)3CHCl3 (5 mol %), (R,R)-LST (15 mol %) was added after 1 h.

[g]

Another portion of Pd2(dba)3CHCl3 (5 mol %), rac- LST (15 mol %) was added after 3.5 h.