Potassium tert-Butoxide

Biographical Sketches

Yong Wang was born in Zhejiang in 1985 and obtained his B.Sc. degree from the Zhejiang University of Technology. Currently he is a postgraduate student supervised by Professors Chengrong Ding and Guofu Zhang in Zhejiang University of Technology. His current research mainly focuses on transition-metal-free cross-couplings.

Introduction

Potassium tert-butoxide (KOt-Bu, mp 256˜258 ˚C), recognized as one of the most commercially available and versatile alkoxide bases in organic synthesis, has attracted increasing attention in recent years, and many excellent examples promoted by KOt-Bu, such as alkylations, intramolecular aldol condensations, Michael additions, ketone cleavages, oxidations and rearrangement reactions have been reported. [¹] As to its continued popularity, the reason may partly be ascribed to the fact that its base strength is highly dependent on the choice of reaction solvent. The range from the strongest to the weakest is listed as follows: KOt-Bu in DMSO, neat KOt-Bu, KOt-Bu in toluene or in THF, and KOt-Bu in t-BuOH. Moreover, ­potassium tert-butoxide also serves as an efficient and powerful base in transition-metal-catalyzed couplings like Suzuki and Buchwald-Hartwig reactions, etc. [²]

Abstracts

(A) With a catalytic amount of potassium tert-butoxide, Cainelli and co-workers have found that the synthesis of primary amine derivatives could successfully be achieved via a rapid 1,3-prototropic rearrangement of N-diphenylmethanimines. [³] Moreover, this mild protocol for transamination can also be applied for aliphatic and ­aromatic aldimines.
(B) Knochel and co-workers [4] have developed a new and efficient synthetic method for the addition of various carbonyl compounds (nitriles, ketones, and imines) to styrenes in the presence of potassium tert-butoxide. The desired products could be obtained in good to excellent yields. It is important to mention that the combination of potassium tert-butoxide with polar solvents, dimethyl sulfoxide or N-methylpyrrolidinone allows the reaction to proceed in mild conditions.
(C) Beller et al. [5] have disclosed a transition-metal-free amination of aryl chlorides in the presence of KOt-Bu, which probably proceeds via the formation of an aryne intermediate. It is interesting that the aliphatic and aromatic amines could react with ortho- and meta-chlorostyrene without palladium to give N-substituted 2,3-dihydroindoles in good yields. In addition, the intermolecular aminations of aryl chlorides with primary and secondary amines could also react smoothly, albeit only meta-substituted anilines were obtained.
(D) Yoshizawa et al. [6] presented highly reactive 1,3-diaryl-2-propynyl trimethylsilyl ethers, which could easily isomerize into the corresponding siloxyallenes using a catalytic amount of potassium tert-butoxide under mild conditions. The obtained intermediates could react in situ with various aldehydes to afford selective β-branched Morita-Baylis-Hillman-type adducts in an one-pot reaction after acid treatment.
(E) Tu and co-workers [7] have developed a concise and transition-metal-free method for the coupling of alkynes and aldehydes. The β,γ-unsaturated enones could be obtained in moderate to good yields in THF in the presence of potassium tert-butoxide at room temperature. However, the reaction of aliphatic aldehydes led to low yields of the desired products.
(F) An efficient and unprecedented synthetic route to dihydroxazine derivatives was developed by Zhou and co-workers, [8] which underwent tandem ring-opening/-closing reactions of N-Ts aziridines and aryl propargyl alcohols. It was interesting that KOt-Bu was found to be an effective promoting reagent for this transformation. This strategy offers an efficient protocol for the construction of six-membered ring systems under mild conditions.
(G) Instead of the employment of highly versatile and noble metals in the catalytic arylation reactions, Itami and co-workers reported for the first time that the coupling between electron-deficient nitrogen-containing heterocycles and iodoarenes could be smoothly promoted by KOt-Bu alone. [9] Later on, the research groups of Shi, [¹0] Hayashi, [¹¹] Lei, [¹²] and Charette [¹³] have reported subsequently on the construction of biaryl compounds from unactivated aromatic rings by the direct C-H activation with a combination of organocatalyst and KOt-Bu. In addition, the mechanism of these transition-metal-free couplings was also interpreted by Studer and Curran recently. [¹4] It was believed that these base-promoted couplings would have a much broader application in organic synthesis.

References

1a Pearson DE. Buehler CA. Chem. Rev.  1974,  74:  45 

1b Friestad GK. Branchaud BP. In Handbook of Reagents for Organic Synthesis: Acidic and Basic Reagents   Reich HJ. Rigby JH. Wiley; New York: 1999.  p.290-296  

Selected literatures for the use of KOt-Bu as a versatile base in metal-catalyzed reactions:

2a Singh R. Viciu MS. Kramareva N. Navarro O. Nolan SP. Org. Lett.  2005,  7:  1829 

2b Li J. Cui M. Yu A. Wu Y. J. Organomet. Chem.  2007,  692:  3732 

2c Blank B. Madalska M. Kempe R. Chem. Eur. J.  2009,  15:  3790 

3 Cainelli G. Giacomini D. Trerè A. Boyl PP. J. Org. Chem.  1996,  61:  5134 

4 Rodriguez AL. Bunlaksananusorn T. Knochel P. Org. Lett.  2000,  2:  3285 

5 Beller M. Breindl C. Riermeier TH. Tillack A. J. Org. Chem.  2001,  66:  1403 

6 Yoshizawa K. Shioiri T. Tetrahedron Lett.  2006,  47:  757 

7 Wang S. Tu Y. Wang M. Tetrahedron Lett.  2006,  47:  8621 

8 Wang L. Liu Q. Wang D. Li X. Han X. Xiao W. Zhou Y. Org. Lett.  2009,  11:  1119 

9a (a)Yanagisawa S. Ueda K. Taniguchi T. Itami K. Org. Lett.  2008,  10:  4673 

9b Yanagisawa S. Itami K. ChemCatChem  2011,  3:  827 

10 Sun C. Li H. Yu D. Yu M. Zhou X. Lu X. Huang K. Zheng S. Li B. Shi Z. Nat. Chem.  2010,  2:  1044 

11 Shirakawa E. Itoh K. Higashino T. Hayashi T. J. Am. Chem. Soc.  2010,  132:  15537 

12 Liu W. Cao H. Zhang H. Zhang H. Chung KH. He C. Wang H. Kwong FY. Lei A. J. Am. Chem. Soc.  2010,  132:  16737 

13 Roman DS. Takahashi Y. Charette AB. Org. Lett.  2011,  13:  3242 

14 Studer A. Curran DP. Angew. Chem. Int. Ed.  2011,  50:  5018