Heck reaction enantioselective

Larhed et al. investigated enantioselective Heck reactions with 2,3-dihydrofuran as alkene [86]. In the coupling with phenyl triflate, conditions previously reported by Pfaltz [87] were attempted under microwave irradiation. Interestingly, the catalytic system Pd2(dba)3/(4S)-4-t-butyl-2-[2-(diphenylphosphanyl)phenyl]-4,5-dihydro-l,3-oxazole, identified by the Swiss team, was found suitable for high-temperature microwave-assisted enantioselective Heck reactions (Scheme 76). Using a proton sponge as a base and benzene as a solvent gave the best conversions (Scheme 76). At tempera-... 

Shibasaki and coworkers [87] described the first enantioselective combination of this type in their synthesis of halenaquinone (6/1-162) (Scheme 6/1.43). The key step is an intermolecular Suzuki reaction of 6/1-159 and 6/1-160, followed by an enantioselective Heck reaction in the presence of (S)-BINAP to give 6/1-161. The ee-value was good, but the yield was low. 

Novel C2-symmetric thiophene-containing ligands have recently been prepared and utilized in asymmetric synthesis. Dithiophene 158 was utilized as a ligand in the asymmetric reduction of p-ketoesters (prostereogenic carbonyl) and acrylic acids (carbon-carbon double bond) <00JOC2043>. Dibenzo[b]thiophene 159 was utilized as a ligand in enantioselective Heck reactions of 2-pyrrolines <00SL1470>. 

Phosphino-imidazoline ligands of this type were originally synthesized by Bu-sacca and coworkers and used in an enantioselective Heck reaction [28]. 

Scheme 16. Results from the enantioselective Heck reaction using BINAP and PHOX.

O. Loiseleur, M. Hayashi, M. Keenan, N. Schmees, A. Pfaltz, Enantioselective Heck Reactions using Chiral PN-Ligands, J. Organomet. Chem. 1999, 576,16-22. 

Intermolecular, enantioselective Heck reactions require a cyclic olefin as substrate, since syn carbopal-ladation of a cyclic olefin results in a geometrically defined a-alkyl-palladium compound. By necessity, the subsequent syn dehydropalladation must take place away from the newly formed chiral centre, thereby affording a chiral product. 

Regio- and enantioselective Heck reactions of 2 3-dihydrofuran with aryl and alkenyl triflates in the presence of the chiral ligand (R)-BITIANP provides 2-substituted 23-dihydro-furans with complete regioselectivity, high enantioselectivity (86-96% ee) and good yields (76-93%) <99CC1811>. A catalytic oxyselenylation-deselenylation reaction of alkenes offers a stereoselective one-pot conversion of alkenes into 2 -dihydrofurans <99EF0797>. 

Nilsson, P., Gold, H., Larhed, M. and Hallberg, A., Microwave-assisted enantioselective Heck reactions expediting high reaction speed and preparative convenience, Synthesis, 2002, 1611-1614. 

Controlling the coordination of palladium intermediates with silver salts was the key to developing highly diastereo- and enantioselective Heck reactions.58 For example, the presence of silver phosphate in the key cyclization step during the synthesis of various alkaloids reversed the stereochemistry at the newly created spiro center (Scheme 10.33).59... 

The Shibasaki cychzation of mc.vo-cyclohexa-1,4-dienes in the presence of a chiral palladium complex and silver carbonate in l-methyl-2-pyrrolidinone is probably the first example of an enantioselective Heck reaction (Scheme 10.34).60 The enantiomeric excess could be slightly improved by replacing the chiral phosphine ligand BINAP with the corresponding less coordinating arsine ligand, as well as replacing silver carbonate with silver phosphate.61,62... 

The Heck reaction in its original form is not a chirogenic reaction. However, the situation changes if cyclic alkenes are employed as a coupling component, as was initially shown by Larock et al. [6]. In such cases, non-conjugated, chiral products of type 6 are formed because only one syn-Y atom is available for f-W elimination in the intermediates of type 7 (Scheme 3). While racemic mixtures are obtained with achiral catalysts, such transformations of course afford the possibility of achieving enantioselective Heck reactions. 

The enantioselective Heck reaction has matured into a powerful method for asymmetric C-C bond formation and has proven its value in several total syntheses. One can expect that it will find many more applications in the future, even in industry. There is still an extensive space for chemists to design new suitable substrates and to search for new effective chiral ligands [23]. 

These and other enantioselective Heck reactions were performed with a variety of chiral ligands (Table 3-8 and Figure 3-1). However, high enantioselectivities could so far only be achieved with BINAP (accessible in both enantiomeric forms) or oxazoline ligands (preferably the bulky 208). The latter is easily obtained as the (S )-enantiomer. 

The general procedure for a silane-terminated intramolecular enantioselective Heck reaction is exemplified by Scheme 3-60 [61a,b, 259]. A mixture of [Pd2(dba)3 - CHCI3] (0.025 mmol,... 

Jachmann, M., Schmalz, H.-G. Enantioselective Heck reactions, in Organic Synthesis Highiights IV136-143 (VCH, Weinheim, New York, 2000). 

Binap 3.43 is also a good ligand for palladium complexes. Although 71-allyl palladium-binap complexes have met limited applications in asymmetric allylation of malonate like derivatives [872], binap-PdCl2 complexes induce enantioselective Heck reactions [902] and 1,4-disilylations of a-enones [903],... 

Heck reactions. The o-oxazolinylphenyl(diphenyl)phosphine ligand 11 is an xcellent ligand to direct enantioselective Heck reactions. On the other hand, the iioxazolinylmethane derivative 12 has been used for the annulation of allenes by means of jnctionalized aryl iodides. ... 

Larhed reported a MW-assisted enantioselective Heck reaction between cyclopen-tene 116 and phenyltriflate 115 using Pd2dba3 as a catalyst in conjunction with... 

Ruthenium-catalyzed asymmetric reductions of aromatic ketones 180 can be performed under microwave irradiation. Moberg [98] described this reaction using a monomode microwave reactor and ruthenium complexes 182 with enan-tiomerically pure chiral diamines 181 (Scheme 5.51). The reaction is very fast and efficient even sterically hindered tert-butylphenylketone, which is normally quite umeactive, was reduced in almost quantitative yield in 3 minutes. The enantio-selectivity was, however, lower than that obtained under standard conditions similarly to that described by Larhed [77] in the enantioselective Heck reaction between cydopentene 115 and phenyl triflate 116 (Scheme 5.33). 

The other approach to an enantiopure AB segment based on the desym-metrization of a meso-compound is related to the catalytic enantioselective Heck reaction [184]. Oestreich et al. [185] developed a highly (92-94% ee)... 

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