Table 1 Investigation of the palladium-mediated cascade C(sp2) & C(sp3)–H activationa

From: Asymmetric total synthesis of benzenoid cephalotane-type diterpenoids through a cascade C(sp2) & C(sp3)–H activation

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Entry

[Pd]

Solvent

Additive (Delay before addition & Addition time)

Resultb

1c

20 mol% Pd(OAc)2

DMF

-

20a (43%), 21 (24%)

2

20 mol% Pd(OAc)2

DMF

-

10a/20a (46%, 1/4.9), 21 (24%)

3 d

20 mol% Pd(OAc)2

DMF

-

10a/20a (45%, 1/5), 21 (23%)

4

20 mol% Pd(OAc)2

DMF

0.4 equiv. KOPiv

10a/20a (34%, 1/4.6), 21 (23%), 22 (21%)

5

20 mol% PdCl2

DMF

0.4 equiv. KOPiv

10a/20a (46%, 1/5), 22 (21%)

6

20 mol% PdCl2

DMF

1.5 equiv. KOPiv (60 s & 30 s)

10a/20a (29%, 4.1/1), 22 (68%)

7

20 mol% PdCl2

DMF

1.8 equiv. KOPiv (60 s & 30 s)

10a/20a (27%, 4.4/1), 22 (73%)

8

20 mol% PdCl2

DMF

2.0 equiv. KOPiv (60 s & 30 s)

10a/20a (23%, 4.4/1), 22 (75%)

9

20 mol% PdCl2

DMF

1.8 equiv. KOPiv (50 s & 30 s)

10a/20a (24%, 4.5/1), 22 (72%)

10

20 mol% PdCl2

DMF

1.8 equiv. KOPiv (70 s & 30 s)

10a/20a (26%, 3.8/1), 22 (72%)

11e

20 mol% PdCl2

DMF

1.8 equiv. KOPiv (60 s & 30 s)

10a/20a (17%, 2.4/1), 22 (79%)

12 f

20 mol% PdCl2

DMF

1.8 equiv. KOPiv (60 s & 30 s)

10a/20a (12%, 2.2/1), 22 (85%)

13 g

20 mol% PdCl2

DMF

1.8 equiv. KOPiv (60 s & 30 s)

10a/20a (10%, 2.2/1), 22 (86%)

14 h

20 mol% PdCl2

DMF

1.8 equiv. KOPiv (60 s & 30 s)

22 (95%)

15

20 mol% PdCl2

PhMe

1.8 equiv. KOPiv (60 s & 30 s)

not detected

16

20 mol% PdCl2

PhCN

1.8 equiv. KOPiv (60 s & 30 s)

10a/20a (<10%, 1/5.6), 22 (33%)

17

20 mol% PdCl2

t-BuCN

1.8 equiv. KOPiv (60 s & 30 s)

10a/20a (<10%, 1.5/1), 22 (56%)

18

20 mol% PdCl2

DMF/PhMe = 1/1

1.8 equiv. KOPiv (60 s & 30 s)

10a/20a (49%, 10/1), 22 (61%)

19

20 mol% PdCl2

DMF/PhMe = 1/2

1.8 equiv. KOPiv (60 s & 30 s)

10a/20a (28%, 16/1), 22 (73%)

20i

20 mol% PdCl2

DMF/PhMe = 1/1

1.8 equiv. KOPiv (120 s & 50 s)

10a (42%), 22 (64%)

21

20 mol% PdCl2

DMF/PhMe = 1/1

1.8 equiv. KOPiv (80 s & 30 s)

10b/20b (38%, 10/1), 22 (67%)

  1. aReaction conditions: 11a or 11b (0.05 mmol), 12 (0.075 mmol), [Pd]: tri(2-furyl)phospine (ligand) = 1: 2, NBE (0.2 mmol), and Cs2CO3 (0.15 mmol) in solvent (1.2 mL) under an argon atmosphere, 120 °C.
  2. bThe ratio of 10a and 20a was determined by 1H NMR spectroscopy. The yields of 10a-b and 20a-b were calculated against 11a-b. The yields of 21-22 were calculated against 12. Isolated yield.
  3. cThe reaction was conducted in 110 °C.
  4. dThe reaction was conducted in 130 °C.
  5. eTriphenylphosphine as ligand.
  6. fTris(4-methoxyphenyl)phosphine as ligand.
  7. gTris[4-(trifluoromethyl)phenyl]phosphine as ligand.
  8. h1,3-Bis(diphenylphosphino)propane as ligand.
  9. i0.9 mmol11a.
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