Yields of Suzuki couplings involving indoles depended upon (i) whether arylboronic acids or arylpinacolboronate esters were used, (ii) whether the heterocycle was the aryl halide or the arylboron coupling partner, and (iii) whether the heterocycle was protected or not. Highest yields, which were unaffected by incorporating Boc or Tos protection at the heterocyclic nitrogen, were obtained when indole bromides were reacted with phenylboronic acids. When indolylboronic acids were reacted with phenyl bromides, yields were somewhat lower and depended on the nitrogen substituent, being highest in the absence of protection, lower in the presence of the Boc group, and lowest of all with the Tos group. Arylpinacolboronate esters were less reactive than arylboronic acids. They required considerably longer reaction times and furnished generally lower yields of biaryl. Furthermore, irrespective of whether the heterocycle was the aryl bromide or the arylpinacolboronate ester, these yields were highest when it was protected with the Tos group. Yields were lower with the Boc group, and unprotected heterocycles gave only traces of biaryl. Careful selection of arylboron reagent, of coupling partner roles, and of protecting groups are essential to ensuring optimum results in these Suzuki couplings. These results may also be relevant to couplings involving other substrates.

Alpha-amino acid derivatives, particularly those of phenylglycine, can suffer significant racemization in Suzuki couplings. When arylpinacolboronate esters are used as coupling partners this unwanted side reaction can be suppressed by the use of Pd(OAc)(2) as Pd(0) source, in the presence of Buchwald's SPhos ligand. The syntheses of biaryl amino acids of tyrosine, phenylglycine, and tryptophan, including Phg-Trp units similar to those found in the chloropeptin family of natural products, are reported.

Reaction conditions considered to be typical in Suzuki couplings can cause significant (up to 34% of the unwanted enantiomer) loss of optical purity in sensitive substrates such as hydroxyphenylglycine 1. This may be remedied using sodium succinate instead of sodium carbonate as base, but chemical yields are somewhat lower. Optically pure biaryl amino acids related to those found in the chloropeptins and vancomycin were synthesized by Suzuki coupling of 1 with indolylboronic acids 6-8 and with cyclic boronic acid 9.

It is found that the product yield depends on: (1) whether arylboronic acids or boronate esters are used, (2) whether indole is the aryl halide or the arylboron coupling partner, and (3) whether indole is protected or not. Best yields are obtained when indole bromides react with arylboronic acids. In these cases the N-substituent has no effect on the yield. Starting from indolylboronic acids and esters the N-substituent play an important role. Interestingly, unprotected indolylboronic acids give better yields than N-protected ones, while N-protected indolylboronate esters give better yields than unprotected ones. -(PRIETO, M.; ZURITA, E.; ROSA, E.; MUNOZ, L.; LLOYD-WILLIAMS*, P.; GIRALT, E.; J.

The kinetics of the reactions of the nitroprusside ion — pentacyanonitrosylferrate(II) — with various secondary amines have been studied in basic media. Two parallel reaction pathways are involved: (i) the reaction of the nitroprusside ion with hydroxyl ions to form Fe(CN)5NO4+2, in which NO−2 is then replaced by the amine; and (ii) the reaction of the nitroprusside ion with two molecules of amine to form the corresponding nitrosamine and the complex Fe(CN)5NHR3‐2. The corresponding rate equations have been obtained and explained by proposed reaction mechanisms. We propose a concerted mechanism for reaction (ii) in which the amine binds the nitrosyl group at the same time as the amine proton is removed by a base catalyst. The resulting nitrosamine complex subsequently undergoes substitution by the amine in a faster step.