An efficient protocol for the generation of carbon monoxide by Zn-mediated reduction of oxalyl chloride has been developed. Oxalyl chloride was applied as an extremely effective substitute for toxic gaseous CO in the palladium-catalyzed alkoxy-/amino-/hydrogen-/hydroxycarbonylation processes providing industrially interesting esters, amides, aldehydes, and carboxylic acids in good to excellent yields. This new procedure can be applied to various carbonylation reactions in the presence of a transition metal catalyst under mild conditions and with a stoichiometric amount of CO source.

We report substantially improved reaction conditions for palladium(II)-catalyzed tandem cyclization-intramolecular oxycarbonylation of (amino)polyols with a terminal double bond, based on utilization of iron pentacarbonyl [Fe(CO) 5 ] as an affordable and safe liquid supply of the carbonyl unit fully replacing gaseous carbon monoxide. Direct comparison with the classical version on a series of previously published substrates illustrates invariably shorter reaction times but comparable yields and selectivity.

The first total synthesis and absolute configuration assignment of protulactone A (1) has been achieved. Four stereoisomers, 1a, ent-1a, 1b, and ent-1b, of this natural polyketide were prepared by chiral pool synthesis starting from l- and d-arabinose, respectively. The absolute and relative configurations of all isomers were assigned by single-crystal X-ray analysis. Target compounds were screened for their in vitro cytotoxicity toward certain human tumor cells (NCI cancer cell line panel).

This work discloses a continuous flow carbonylation reaction using iron pentacarbonyl as source of CO. The described transformation using this surrogate was designed for use in commonly accessible flow equipment. Optimized conditions were applied to a scalable synthesis of the natural compound isolated from perianal glandular pheromone secretion of the African civet cat. In addition, a flow Pd-catalyzed carbonylation of aryl halides was successfully reported.

A new protocol for the generation of carbon monoxide by the dehydration of glyoxylic acid has been developed. Glyoxylic acid was applied as an environmentally friendly and cheap substitute for toxic and gaseous CO in the palladium-catalyzed carbonylation reactions providing industrially interesting products in good to excellent yields.Carbon monoxide as an important chemical substance has found an application in many organic reactions. Especially, the transition-metal-catalyzed transformations [1] represent an elegant method for the efficient instalment of a carbonyl group into organic molecules providing various carboxylic acid derivatives, ketones and aldehydes, which are of relevant interest in the pharmaceutical and agrochemical industry. [2] However, the high toxicity of CO gas and the associated need for special handling considerably disadvantages the use of carbonylation strategies in laboratory and industrial environment. Such safety considerations has resulted in an increased demand for the development of new and laboratory-safer sources of CO. [3] To this date, many CO-surrogates have been explored for the application in "CO-free" carbonylation. [4][5][6][7][8][9][10][11][12] These suppliers include metal carbonyls such as [Mo(CO) 6 ], [4a-c] [Cr(CO) 6 ], [4d] [W(CO) 5 ], [4d-f] [Fe(CO) 5 ], [4g, h] acid chlorides [5] (COgen,[5a, b] pivaloyl chloride [5a] ), silacarboxylic acid, [6] formates, [7] formamides, [8] formaldehyde, [9] chloroform [10] and oxalyl chloride. [11] Generally, all these CO substitutes have been successfully applied in carbonylation reactions generating CO gas in situ or ex situ by using a two chamber reaction system. [5, 11] In terms of reaction efficiency and the avoidance of waste generation, a procedure for Heck, Songashira and radical carbonylation deserves a special attention. In method described by Ryu et al., [12] the carbon monoxide was generated ex situ by the Morgan reaction (dehydration of common and cheap formic acid with sulfuric acid). Recently, we have reported a reaction system for carbonylation of aryl halides using CO generated ex situ by Zn-mediated reduction of oxalyl chloride. [11c] A substoichiometric amount of CO-surrogate was sufficient for effective Pd-catalyzed carbonylative cou-plings. In our continuing effort to develop new carbonylation processes, [4g, h, 11c] we herein report a novel protocol for generation of CO gas and its direct application in palladium-catalyzed carbonylations. Two moles of carbon monoxide are generated in an efficient manner by dehydration of glyoxylic acid monohydrate using sulfuric acid.In 1907 H. D. Dakin [13] published a study describing the act of formaldehyde, glyoxylic acid and oxidizing substances on tryptophan and skatol (Hopkin-Cole test). He proposed a formation of glyoxylic acid by the oxidation of intermediary formed glycolaldehyde (Scheme 1, eq. 1). Despite the fact, that the formation of glyoxylic acid has not been satisfactory demonstrated, author suggested its theoretical decomposition to CO 2 , ...