Double Baylis-Hillman reaction

Shi, M., Xu, Y.-M. An Unexpected Highly Stereoselective Double Aza-Baylis-Hillman Reaction of Sulfonated Imines with Phenyl Vinyl Ketone. J. Org. Chem. 2003, 68, 4784-4790. 

In this subsection, we describe a couple of examples taken from the recent literature, in which the Baylis-Hillman reaction has been employed for the construction of new carbon-carbon bonds. The Baylis-Hillman reaction proceeds in a catalytic cycle propagated by a nucleophilic catalyst (584). The nucleophilic catalyst initiates the cycle by Michael addition to a double bond bearing an EWG (586 or 590). The carbon a to the EWG is acidic and may react with an electrophile. Finally, the nucleophilic catalyst is eliminated, completing the cycle (Scheme 122). The most frequently used catalysts are quinuclidine, DABCO, phosphines, thiopheno-lates, and selenophenolates. The reaction rate of a catalytic Baylis-Hillman reaction approaches a maximum at a certain temperature and declines upon further heating, as the equilibrium concentration of (587) becomes very small. In the first example, the electrophilic component of the reaction was immobilized on a solid phase and the nucleophile was in solution, while in the other example the situation was reversed (Scheme 122). 

The Baylis-Hillman reaction involves the reaction of an aldehyde with an a,fi-unsaturated ketone in the presence of a tertiary amine. This results in the aldehyde adding at the a-position of the carbon-carbon double bond. The reaction is conventionally carried out without a solvent however this causes problems if the starting materials are solids. Hence the reaction was investigated in ionic liquids such as [BMIM][BF4] and [BMIMjjPFe] [210]. The reaction of methyl acrylate with ben-zaldehyde proceeded 11 to 34 times faster in the ionic liquids than in the solvent acetonitrile. Various Lewis acidic additives had little effect on the reaction, with the exception of lithium perchlorate, which gave a 53 times rate enhancement. This reaction is shown in Scheme 5.2-85. 

Sanhao et al. have proposed to utilise a Baylis-Hillman type reaction between dialdehydes and diacrylates to obtain polymers with a polyester backbone and alcohol and double bond side-groups [87]. The authors reported this material to be a very interesting intermediate towards side-chain modified polymers. 

Contra-Peterson elimination also occurred in Morita-Baylis-Hillman-type reactions of 1-silylcyclopropene 101. Addition of the nucleophilic catalyst tris(2,4,6-trimethoxyphenyl)phosphine (TTMPP) at the 2-position of the alkene and condensation of the anion with an aldehyde led to 1,3-Brook rearrangement, with expulsion of the catalyst to regenerate the cyclopropene double bond in product 102. ... 

The reactivity of activated C-C double bonds with NHC has been reviewed more specifically. This report details the umpolung reaction involving Michael acceptors, the use of carbenes in Morita-Baylis-Hillman as well as in various cycloadditions. The catalysis of alkyne cycloaddition with nitrile oxide is also covered. 

The Morita-Baylis-Hillman (MBH) reaction is described as the coupling between the a-position of an activated double bond and an sp electrophilic carbon (typically an aldehyde, but also an imine) using an appropriate catalyst, normally Lewis bases [21]. Shi and coworkers showed that imidazole and proline formed an efficient co-catalytic system for carrying out the MBH reaction, but with low ee [22]. 

Under high pressure (10 kbar), the p-hydride elimination is retarded and the metastable a-alkylpalladium halide may insert into the double bond of a second acrylate to eventually— after double shift— yield a diethyl (arylmethylene)glutarate (Scheme 5-33). Alternatively, the acrylate may dimerize first e.g., via a Baylis-Hillman-type reaction), and the diethyl 2-methyleneglutarate subsequently undergo a Heck arylation. 

The introduction of the activated allylic bromides and Morita-Baylis-Hillman acetates and carbonates pioneered the development of a number of phosphine-catalyzed reactions in subsequent years [45]. Interestingly, the asymmetric variant of this type of transformation only appeared in the literature seven years later. In 2010, Tang, Zhou, and coworkers disclosed a highly enantioselective intramolecular ylide [3-f2] annulation using spirobiindane-based phosphine catalyst 31 (Scheme 20.27). BINAP was found inactive in this reaction even at an elevated temperature (70°C). Notably, both optically active benzobicyclo[4.3.0] compounds 32 and 32 with three continuous stereogenic centers could be obtained as major products in high yields and stereoselectivities just by a choice of an additive [Ti(OPr )4], which can block the isomerization of the double bond [46]. 

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