Written by: Dr. Sharbil J. Firsan

A new twist on the Hiyama cross-coupling reaction has recently been reported by Alacid and Najera.  It features a ligandless, Pd-catalyzed cross-coupling that is carried out with aqueous sodium hydroxide as promoter and tetra-n-butylammonium bromide (TBAB) as additive at 120 ^oC under conventional or microwave heating.  Good yields, stereoselectivities, low catalyst loadings, and ease of recovery of the Pd catalyst are characteristics of this reaction protocol.

Alacid, E.; Najera, C. J. Org. Chem. 2008, 73, 2315.  See also Denmark, S. E.; Ober, M. H. Aldrichimica Acta 2003, 36, 75.

Written by: Dr. Sharbil J. Firsan

Dennis Hall and co-workers have recently disclosed the remarkable ability of ortho-bromo- and ortho-iodophenylboronic acids, [2-BrC₆H₄B(OH)₂] and [2-IC₆H₄B(OH)₂], to catalyze the direct amidation of free carboxylic acids with amines and the Diels–Alder reaction of free alpha,beta-unsaturated carboxylic acids with simple dienes.  The noteworthy features of this discovery are:

• 2-BrC₆H₄B(OH)₂ and 2-IC₆H₄B(OH)₂ are better catalysts for the direct amidation than the hitherto most efficient catalyst for the reaction, namely 3,4,5 F₃C₆H₂B(OH)₂.
• Both reactions take place at room temperature in an atom-economical, byproduct-free fashion.
• Both are operationally simple affording the pure products after a simple filtration and acid–base extractions (no chromatographic separations required).
• The boronic acid catalyst is recovered from the basic aqueous phase in high yield.
• The direct amidation reaction is broad in scope, and the Diels–Alder reaction remarkably selective.
• The two reactions can be combined in an efficient, one-pot, two-step cascade sequence that is promoted by a single catalyst.

Al-Zoubi, R. M.; Marion, O.; Hall, D. G. Angew. Chem., Int. Ed. 2008, 47, 2876.  For selected recent reviews on organocatalysis, see: (a) Longbottom, D. A.; Franckevicius, V.; Kumarn, S.; Oelke, A. J.; Wascholowski, V.; Ley, S. V. Aldrichimica Acta 2008, 41, 3.  (b) Lelais, G.; MacMillan, D. W. C. Aldrichimica Acta 2006, 39, 79.

Written by: Dr. Sharbil J. Firsan

Bolshan and Batey recently reported the copper-catalyzed, stereoselective cross-coupling of amides with potassium alkenyltrifluoroborates, leading to high yields of the corresponding enamides, which are valuable synthetic intermediates and important structural features in many natural products.  Under optimized conditions, this reaction offers the following advantages over other enamide syntheses:

• Potassium alkenyltrifluoroborates are air- and moisture-stable, and are readily available.
• The process is catalytic in copper and does not require a base or a heterocyclic ligand.
• It takes place under mild temperatures.
• Is general in scope and gives rise to high yields and stereoselectivities
  
  

  

Bolshan, Y.; Batey, R. A. Angew. Chem., Int. Ed. 2008, 47, 2109.

Written by: Dr. Sharbil J. Firsan

A highly enantioselective and organocatalytic Michael addition of a-substituted aldehydes to nitroethylene has been reported by Gellman and co-workers.^1,2  The metal-free catalyst system consists of (S)-diphenylprolinol silyl ether as the catalyst (2 mol %) and 3-nitrobenzoic acid as the co-catalyst (20 mol %).  When followed by NaBH₄ reduction of the aldehyde group of the addition product, the method leads to beta-substituted delta-nitrobutanols in excellent yields and enantioselectivities.  In turn, these butanols can be readily converted into the corresponding N-protected gamma²-amino acids—important building blocks for gamma-peptides and heterogeneous-backbone foldamers—by a short and operationally simple sequence of hydroxyl group oxidation, nitro group reduction, and amino group protection.

(1) Chi, Y.; Guo, L.; Kopf, N. A.; Gellman, S. H. J. Am. Chem. Soc. 2008, 130, ASAP.  (2) For a recent review on organocatalytic conjugate additions utilizing pyrrolidinyltetrazoles as organocatalysts, see Longbottom, D. A.; Franckevicius, V.; Kumarn, S.; Oelke, A. J.; Wascholowski, V.; Ley, S. V. Aldrichimica Acta 2008, 41, 3.