MgI2-catalyzed halo aldol reaction: a practical approach to (E)-?-iodovinyl-??-hydroxyketones (original) (raw)
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MgI2-catalyzed halo aldol reaction: a practical approach to (E)-β-iodovinyl-β′-hydroxyketones
Organic & biomolecular chemistry, 2004
A novel generation of 1-iodo-3-siloxy-1, 3-butadienes has been developed by reacting trimethylsilyl iodide (TMS-I) with α, β-unsaturated ketones in dichloromethane at 0 C without the use of any catalyst. The halo aldol reaction of these butadiene intermediates with aldehydes was efficiently carried out by using magnesium iodide as the catalyst. Twelve β-iodo-α, β-unsaturated-β!-hydroxyketones (halo aldols) have been synthesized under the new condition with excellent geometric selectivity and good chemical yields (> 80% ...
Tetrahedron, 2004
The first example of a direct aldehyde–ketone coupling using the secondary amine piperidine as base in the presence of MgI2 to generate high selectivity of anti-aldol products from unmodified ethyl ketones in high yield is reported. The coupling reactions were carried out in a one-pot reaction by mixing four reaction components at room temperature. In the case of unsymmetrical ketones, addition was made to the less hindered α-side.
The Journal of Organic Chemistry, 1984
The introduction of neighboring functional groups in a sequence directed to the total synthesis of natural products, including macrolide antibiotics, is of great importance in modern synthetic strategy.l In previous papers we described new methods for regio-and stereocontrolled functionalization of the double bonds of allylic and homoallylic alcohols. Thus amino diols and hydroxyaziridines were obtained via iodoxazolines and iododihydrooxazines,2 while 1,2-and 1,3-diols, triols, and expoxy alcohols were synthesized by starting from cyclic iodo carbonate^,^^^ versatile intermediates susceptible to several chemical transformations.
Enantioselective organocatalytic aldol reaction of unactivated ketones with isatins
Tetrahedron Letters, 2011
Enantioselective organocatalytic direct aldol reaction of unactivated ketones with various isatin derivatives was developed using cinchonine based urea ligand employing a noncovalent catalysis mechanism. Using this protocol we can access functionalized 3-alkyl-3-hydroxyindolin-2-ones in high yields with good to excellent enantioselectivities.
Asian Journal of Organic Chemistry, 2019
A metal-free regioselective synthesis of α-aryl ketone from corresponding bromohydrin via cooperative cascade effect of [hmim]Br and tetrabutylammonium fluoride under microwave irradiation is reported. Applications of the protocol are illustrated by synthesis of drug intermediates piperonyl-methyl ketone and 2-tetralone. Interestingly, direct regioselective transformation of epoxide and 1,2-diol into α-aryl ketone under neat [hmim]Br has also been realized. Advantages of this method are demonstrated through the recyclability of [hmim]Br-tetrabutylammonium fluoride catalytic system and gram scalability. Wacker process [1] has been a staple reaction for transformation of terminal alkene into aldehyde or ketone depending on the oxidant used along with the palladium catalyst (Scheme 1). However, the transformation of internal alkene viz. phenylpropene, usually provides isomeric mixture ketones i. e. propiophenone (i. e. 1-ketone) and α-aryl ketone (i. e. 2-ketone) in varying ratio catalyst (Scheme 1A). [1d-f] Although relentless efforts have been devoted towards efficient regioselective Wacker-type [2] reaction of internal alkene by inserting directing groups in the alkene however the existing methods are limited due to requirement of harsh reaction conditions, low yield etc. On the other hand, 3-phenyloxirane (epoxide) [3] or phenylpropane-1,2-diol [4] are also widely exploited as a versatile precursor to regioselectively obtain the desired carbonyls (1/2ketone or aldehyde) in high yield using a variety of catalysts viz. InCl 3 , [3b] BF 3 .Et 2 O [4a] etc. Recently, Coates [5] effectively utilized [Lewis acid] + [Co(CO) 4 ] À catalyst for regioselective isomerization of 3-phenyloxirane into α-aryl ketone as the major product over propiophenone. A different pathway utilizing highly reactive and easily available halohydrin [6] (β-halo alcohol) as an alternative precursor for net transformation of alkene into carbonyls including propiophenone [7] or α-aryl ketone [8] has also been explored (Scheme 1A). Literature reveals that β-halohydrin could be readily converted into propiophenone using various catalysts [7] such as Pd(OAC) 2 /P(o-Tol) 3 , [7a-b] CoCl(Ph 3 P) 3 /Et 3 N [7c] and photochemical reaction [7d] in benzene in the presence of p-toluenesulfonic acid. However their conversion into α-aryl ketone is sparsely reported, despite the central importance of α-aryl ketones as key intermediate [9] for various important compounds viz. diarylisoxazoles, [9a] stilbenes [9b] and anthranilodinitrile [9c] etc as well as it's application in pharmaceuticals and as bioactive molecules. The reported protocol employs catalyst such as highly pyrophoric diethyl zinc [8a] and air-sensitive Grignard reagent. [8c] Recently, Takemoto and co-workers [10] reported rearrangement of tertiary halohydrinsilyl ether into α-aryl ketone derivative using NIS and NISac induced desilylative semipinacol reaction via CÀ X bond cleavage. Many of the existing strategies still suffer from various limitations such as the use of expensive and toxic transition metal catalysts, formation of regioisomers, lack of catalyst recyclability. Moreover, the requirement of welltailored tertiary β-halohydrin [8c,e] is a major limitation towards exclusive formation of α-aryl ketone as switching to secondary β-halohydrin results in loss of selectivity. On the other hand, some notable efforts have also been made towards selective formation of α-aryl ketone [11] from internal alkyne, [11a] diazo compounds via rhodium catalyzed selective de-esterification and decarbonylation, [11b] diazonium tetrafluoroborate salts. [11c] As such, a more general and viable greener reaction for regioselective synthesis of α-aryl ketone from versatile secondary β-halohydrin is welcomed as a complementary approach to the existing strategies.
Different catalysts derived from Keggin-type heteropoly compounds were prepared and their catalytic activities have been compared in the iodination of benzyl alcohol with KI under mild reaction conditions. A high catalytic activity was found over tungstophosphoric acid supported on silica and titania. The effect of catalyst loading, iodine source and the nature of substituents on the aromatic ring of benzyl alcohol were investigated. Finally, several competitive reactions were studied between structurally diverse alcohols. This protocol provides a mild and expedient way for the conversion of various alcohols to their corresponding alkyl iodides with high selectivity.