Cleavage of Cyclobutanols and Cyclobutanones

Literature Report VII Transition Metal-Catalyzed Enantioselective C-C C Bond Cleavage of Cyclobutanols and Cyclobutanones Huang, W.-X. checker: Yu, C.-B. 2014-04-2904 29 1

Contents 1. Background Information 2. Pd-Catalyzed Enantioselective C-C Bond Cleavage 3. Rh-Catalyzed Enantioselective C-C Bond Cleavage 4. Ni-Catalyzed Enantioselective C-CC Bond Cleavage 5. Summary 2

1. Background Information Figure 1. Inert C-C Bond 3

Figure 2. Two Major Pathways for C-C Activation 4

Figure 3. General Synthetic Strategies for the Cyclobutanols Cramer, N. et al. Synlett 2011, 4, 449. 5

2. Pd-Catalyzed Enantioselective C-C Bond Cleavage Figure 4. Pd-Catalyzed xidative Ring Cleavage of tert-cyclobutanols R H Pd(Ac) 2, Pyridine, MS 3A Ethyl Acrylate, Toluene 80 o C, 2 R -HPdXL 2 R -Carbon Elimination R PdXL 2 PdXL 2 Uemura, S. et al. J. Am. Chem. Soc. 1999, 121, 2654. 6

Figure 5. Pd-Catalyzed Enantioselective C-C Bond Cleavage of Cyclobutanols Uemura, S. et al. J. Am. Chem. Soc. 2003, 125, 8862. 7

Figure 6. Pd-Catalyzed Asymmetric Arylation of Cyclobutanols H Ph Ph H + PhTf H Me H Pd(Ac) 2, L*, Cs 2 C 3 Ph NMe 2 Ph THF, Reflux Fe PPh 2 Ph L* Entry Cis/Trans GLC yields (%) Ee (%) 1 80/20 16 36 2 85/15 36 43 3 90/10 40 50 4 95/5 33 54 5 98/2 42 59 8

Figure 7. Asymmetric Arylation of tert-cyclobutanols with Aryl Bromide Uemura, S. et al. J. Am. Chem. Soc. 2003, 125, 8862. 9

3. Rh-Catalyzed Enantioselective C-C Bond Cleavage Figure 8. Enantioselective β-alkyl Cleavage by Rhodium 10

Figure 9. Rh-catalyzed Addition and Ring-pening Murakami, M. et al. rg. Lett. 2006, 8, 3379. 11

Figure 10. Rh-Catalyzed Reaction of Cyclobutanones R [Rh(cod)H] 2, Chiral Ligand Me R H Toluene, rt, 17-26 h R Addition R -Carbon Elimination [Rh] R [Rh] [Rh] Murakami, M. et al. J. Am. Chem. Soc. 2007, 129, 12086. 12

Figure 11. Deuterium-Labeling Experiment Murakami, M. et al. J. Am. Chem. Soc. 2007, 129, 12086. 13

Figure 12. Asymmetric Synthesis of 4,4-Disubstituted 3,4-Dihydrocoumarins 14

Figure 13. C-C Bond Activation for the Synthesis of Cyclic Ketones R 1 H H R 2 ArBr Pd(Ac) 2 (5 mol%), L* (10mol%) Cs 2 C 3, Toluene, 50 o C H R 2 R 1 Ar 32 Examples Up to 95% ee Uemura, S. et al. J. Am. Chem. Soc. 2003, 125, 8862. Cramer, N. et al. Angew. Chem. Int. Ed. 2008, 47, 9294. 15

Figure 14. Rhodium-Catalyzed C-C Activation of Cyclobutanols Cramer, N. et al. Angew. Chem. Int. Ed. 2008, 47, 9294. 16

Figure 15. Rh-Catalyzed Rearrangement of Allylic tert-cyclobutanols Cramer, N. et al. Chem. Eur. J. 2010, 16, 3383. 17

Figure 16. Mechanistic Manifold for the bserved Product Distribution Cramer, N. et al. Chem. Eur. J. 2010, 16, 3383. 18

Figure 17. Enantioselective Synthesis of Indanols from tert-cyclobutanols Cramer, N. et al. Angew. Chem. Int. Ed. 2009, 48, 6320. Murakami, M. et al. Chem. Eur. J. 2009, 15, 12929. 19

Figure 18. Enantioselective Synthesis of Indanones from tert-cyclobutanols Hartwig, J. F. et al. J. Am. Chem. Soc. 2006, 128, 3124. Cramer, Ca e, N. et al. Synlett 2010, 0, 1699. 20

Figure 19. Rh-Catalyzed 1,4-Silicon Shift of Unactivated Silanes Cramer, N. et al. Angew. Chem. Int. Ed. 2010, 49, 10163. 21

Figure 20. Rh-Catalyzed Ring-pening/Protonation Process Cramer, N. et al. J. Am. Chem. Soc. 2010,, 132,, 5340. 22

Figure 21. 1,3-Rh Shift Leads to Diastereoselective Deuteration [Rh]/L*, dioxane, 110 o C Et D Bn D 20 equiv. D 2 Bn Ph Et Ph trans [Rh] cis Et L* Bn H H ent-l* Ph 1,3-Rh shif t H D 2 H Ph D 2 H Et Bn H D Ph Et Bn H Rh Et Bn D H Ph (2S,3R) (2R,3R) 85% D, dr 86:14 85% D, dr 15:85 Cramer, N. et al. J. Am. Chem. Soc. 2010, 132, 5340. 23

Figure 22. Rh-Catalyzed Carboacylation of lefins: R 1 R 2 [Rh(cod)Cl] 2,(R)-DTBM-SegPhos 1,4-Dioxane, 133 o C R 1 R 2 1) [Rh], THS, ph = 7.6, Hexane, H 2 (800 psi) 14 Examples Up to 97% yield, 99% ee 2) TPAR, NM, 4A MS * * * * R 1 * R 2 3Examples Up to 70% yield Dong, G.-B. et al. J. Am. Chem. Soc. 2012,, 134,, 20006. 24

Figure 22. Rh-Catalyzed Enantioselective C-C Activation of Cyclobutanones Cramer, N. et al. Angew. Chem. Int. Ed. 2014, 53, 3001. 25

4. Ni-Catalyzed Enantioselective C-C Bond Cleavage Murakami, M. et al. Angew. Chem. Int. Ed. 2012, 51, 2485. 26

5. Summary Introduction of the Corresponding Author Masahiro Murakami Kyoto University Nicolai Cramer EPFL Lausanne Guangbin Dong University of Texas at Austin 27

5. Summary Pd-Catalyzed Asymmetric C-C Bond Cleavage R 1 R 3 ArPdXL n L n ArPd -PdL n Ar R 2 R R H 1 R 3 1 R 3 R 2 R 2 Enantioselective -Carbon Elimination Ni-Catalyzed Asymmetric C-C Bond Cleavage [Ni 0 ] -[Ni 0 ] Asymmetric xidative Cyclization Diastereoselective -Carbon Elimination Ni 28

Rh-Catalyzed Asymmetric C-C Bond Cleavage R 1 R 2 H R 3 R-[Rh] -RH R 1 R 2 [Rh] R 3 R 3 -[Rh] R 1 R 2 [Rh] R 2 R 1 R 3 R Me R 1 H R 3 i Pr R 2 R 1 R R 2 R 1 R R 1 [Si] H R 3 CH 3 R 1 Me R 1 R 2 R 3 Intramolecular cyclization to an activated allene -Hydride elimination Intramolecular cyclization to terminal enones 1,4-Rh/Si shifts by C(sp 2 )-Si activation 1,4-Rh/H shifts by C(sp 2 )-H activation 1,3-Rh/H shifts by C(sp 3 )-H activation to ketone 29

The selective functionalization of carbon-carbon (C-C) σ bonds by transition-metal catalysts is a prime challenge for organometallic chemistry and represents a complementary synthetic strategy that enables uncommon retrosynthetic disconnections. Important progress has been made over the past decade in the field of C-C activation. However, despite their recognized importance, the development of asymmetric reactions lags behind. For instance, most enantioselective variants have been reported for the β-carbon elimination mechanism that allows C-C bond cleavages adjacent to tertiary alcohols. For reactions involving C-C cleavage through oxidative addition at transition metals, strained ketones have proven highly versatile. 30

In summary, we report an asymmetric rhodium(i)-catalyzed C-C activation of cyclobutanones that gives efficient access to the valuable bicycloheptanone scaffold with exceptionally high enantioselectivity. This demonstrates the feasibility of selective oxidative additions of enantiotopic C-C bonds at high reaction temperatures. The method shown allows rapid access to complex cyclic structure and serves as a blueprint for the design of further asymmetric C-C bond activations. 31

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