Acetates Baylis-Hillman

Conjugate dcLiicii of nkro ilkdnes to illyl Baylis-Hillman acetates in the pesence of NaOH (0.6 N in THF ves 2-alkylidene-4-nitro ketones with high sieteoselecdvity these are convened via the Nef teacdon into the conesponding 1,4-diketones fEq. 4.1... 

Moreover, a twofold SN -type domino reaction was reported by Krische and coworkers for the synthesis of y-butenolides 2-229 (Scheme 2.53) [128]. Treatment of Morita-Baylis-Hillman acetates 2-226 with trimethylsilyloxyfuran (2-227) in the presence of triphenylphosphane in THF at 0 °C led to 2-229 in yields of up to 94% and diastereoselectivities of >95 5. 

Conjugate addition of nitroalkanes to ailyl Baylis-Hillman acetates in the presence of NaOH (0.6 N) in THF gives 2-alkylidene-4-nitro ketones with high stereoselectivity these are converted via the Nef reaction into the corresponding 1,4-diketones (Eq. 4.119).164... 

Baylis-Hillman acetates have been conveniently transformed into tri/tetracyclic heterocyclic frameworks containing an azocine moiety via a one-pot multistep protocol involving alkylation, reduction, and cyclization sequence <2007OL2453>. Treatment of Baylis-Hillman acetate 284 with 1,3-cyclohexanedione in the presence of K2CC>3, followed by treatment of the resulting product with Fe/AcOH, gave 77% fused azocine 285 (Scheme 119). 

As shown in Equation (17), 2-trimethylsilyloxyfuran also participated in a triphenylphosphine-catalyzed substitution reaction with Morita-Baylis-Hillman acetates to provide interesting 7-butenolides regio- and diastereoselec-tively <2004AGE6689>. However, the reaction mechanism (vinylogous Michael vs. Diels-Alder) has not been distinguished. 

This reaction has been further extended to a catalytic procedure for the synthesis of allyl aryl sulfone derivativesl47 from Baylis-Hillman acetates 145 and sulfonyl hydrazides 146 using BU4NI as the catalyst and TBHP as an oxidation agent in water (Scheme 4.74) [116],... 

The isomerization of simple allyl acetates proceeds by 1,3-migration via a six-membered cyclic acetoxonium intermediate and is most efficiently catalyzed by cationic gold(I)-NHC complexes. The rearrangement is carried out either by refluxing in dichloroethane or with microwave heating. By contrast, the allylic rearrangement of Baylis-Hillman acetates already occurs at room temperature in the presence of AuCl and AgOTf. ... 

A twofold Sjj type domino organocatalytic reaction for the synthesis of y-butenolides 28 has been reported by Krische and coworkers [19], by treatment of Morita- Baylis- Hillman acetates 26 with trimethylsilyloxyfuran (27) in the presence of triphenylphosphine to afford 28 in yields up to 94% and diastereoselectivities of >95 5 dr (Scheme 4.6). 

In 2004, Krische and colleagues demonstrated that exposure of Morita-Baylis-Hillman acetates to tertiary phosphine catalysts in the presence of 4,5-dichlorophthalimide enabled regiospecific allylic substitution through a tandem Sn2 -Sn2 mechanism. Through the use of the chiral phosphine catalyst, (i )-Cl-MeO-BIPHEP, the racemic Morita-Baylis-Hillman acetate depicted in Scheme 2.108 was converted into the corresponding enantiomerically enriched allylic amination product, thus establishing the feasibility of DKR. 

Scheme 2.108 DKR of Morita Baylis Hillman acetate catalysed by (R)-Cl-MeO-BIPHEP.

The reaction of several Morita-Baylis-Hillman acetates of 2-azidobenzaldehydes with triethyl phosphite has been described. The products are the 1-diethylphos-phono-l,2-dihydroquinolines (49) and/or the 3-acetoxymethylquinolines (50). The 2 1 1 addition of arysulfonylisocyanates, dialkyl acetylendicarboxylates and dialkyl trialkylsilylphosphites affords the hydantoins (51) as a diastereomeric mixture in excellent yields. ... 

In the course of developing an easy access to chiral y-butenolides, Shi et al. have established an efficient multifunctional chiral binaphthyl phosphine-catalysed allylic substitution of Morita-Baylis-Hillman acetate with 2-tri-methylsiloxy furan. The regjospecific allylic substitution occurred to provide the xyra-y-butenolide in good to excellent yield, high regjoselectivity and excellent enantioselectivity by using water as an additive. The scope of this reaction could be successfully extended to a variety of Morita Baylis Hillman acetates, as shown in Scheme 5.10. 

Scheme 4.19 Baylis-Hillman acetates 30 in the synthesis of a-alkylidene-S-lactones 75.

Scheme 4.20 Sfj2 alkylation of Baylis-Hillman acetates 30.

Moreover, the cross-couplings between hexamethyldisilane and Baylis-Hillman acetate (79) can also be catalyzed by use of Pd2(dba)3. Accordingly, 3-substituted-2-carbonylallylsilanes (80) are produced in high yields with high regio- and stereoselectivity (eq 37). 2... 

Baylis-Flillman acetates 87 and 89 were involved in the nucleophilic substitution with sodium azide followed by the copper(I) catalyzed 1,3-dipolar cydoaddition of the generated azide to terminal alk5mes (Scheme 51) [80]. The geometry of the products was found to depend on the type of substituents at the Baylis-Hillman acetates. In case of methoxycarbonyl substituent, E-isomers 88 were isolated, while cyano-substituted substrates 89 afforded Z-isomers 90. The reaction of aliphatic alkynes with long chain gave lower yields (e.g., 88, R=hexyl, 58% R=octyl, 42%). It should also be noted that with respect to other solvents, PEG 400 allowed performing the reaction in the absence of... 

Yadav et al made use of InBr3 to catalyze the Sn 2 reaction of Baylis-Hillman acetates with indoles for the synthesis of substituted indoles [161]. The authors had also reported that InBr3 was superior to In(OTf)3, Bi(OTf)3, Sc(OTf)3 or Yb(OTf)3 (Figure 8.70). 

Fig. 8.70 Sim2 reaction of Baylis-Hillman acetates with indoles catalyzed by lnBr3.

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]. 

A rapid S allylic substitution of Baylis-Hillman acetates with ethyl(triphenyl phosphoranylidene) acetate was reported by Yadav et al. (2007) to give ethyl-5-aryl or alkyl-(E)-pent-4-enoates with high (E)-stereoselectivity under microwave irradiation. 

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