Baylis-Hillman-type adducts

A new method has been developed for the synthesis of ( )-3-methyl Baylis-Hillman-type adducts with high E/Z (>93%) selectivity in modest to good yields. The process consists of two steps an indium-mediated allylation reaction and a simple base-catalyzed isomerization step (Eq. 8.61). Various aldehydes were allylated with allyl bromides using indium under very mild conditions in aqueous media and thus converted to the Baylis-Hillman-type adducts.150... 

Li s group reported the first asymmetrically catalyzed addition of 1-siloxy-substi-tuted 3-iodoallenes 71 to carbonyl compounds employing N-heptafluoropropyloxaza-borolidine 73 as a chiral catalyst (Scheme 8.20) [67]. The resulting /i-iodo Baylis-Hillman-type adducts 74 are available in good yield and with enantioselectivities up to 98% ee. 

Scheme 9. Asymmetric synthesis of Baylis-Hillman-type adducts via a chiral acetylenic ester titanium alkoxide complex (Sato et al.).

The asymmetric catalytic aldol reaction of silyl allenolates ICH=C=CR2OSiMe3 with aldehydes R CHO has been achieved by Li et al. by using N-C3F7CO oxazaborolidine as the catalyst [43], The fluoroacyl group of the catalyst was found to be crucial for control of enantioselectivity. The reaction provides the first enantioselective approach to / -halo Baylis-Hillman-type adducts. 

A review on ynolates, including the synthesis of p-lactones, has appeared <03S2275>. Morita-Baylis-Hillman-type adducts have been converted into a-alkylidene-p-lactones 65, which on reaction with dimethyltitanocene can be transformed into 3-alkylidene-2-methyleneoxetanes <03OL399>. Lactones 66 have been obtained via the cinchona alkaloid-catalyzed dimerization of monosubstituted ketenes <03OL4745>. The PdCh-promoted synthesis of P-lactones 67 have been achieved via cyclocarbonylation of 2-alkynols <03OL4429>. 

A general, one-pot synthesis of substituted tetraethyl 2-aminoethylidene-1,1-bisphosphonates (133) has been developed by Gajda. The direct and efficient conversion of the latter into aza-Moritae-Baylis-Hillman-type adducts (134), via the Horner-Wittig reaction with paraformaldehyde, has been also elaborated (Scheme 44). 

A titanium(iv) chloride mediated Baylis-Hillman-type or aldol reaction between a-ketoesters and cyclohex-2-enones has been studied (Equation (13)).77 The steric effect of the R2 substituent is crucial for the reaction pathway since the aldol reaction only proceeds with the unsubstituted cyclohexenone (aldol adduct 71 with R2 = H to a small extent the Baylis-Hillman reaction occurs), whereas with the substituted substrate (R2 = Me) gives exclusively the Baylis-Hillman adduct 72. 

Other Transition Metal Catalysts. The continuous search of other transition metals catalysts is not disturbed during the exploration of new catalysts for the aldol reaction. At present, the application of groups 5-7 and 12 metal as the synthetically useful catalysts for aldol reactions is only limited to vanadium and zinc. In 2001, Trost and co-workers reported a vanadium-catalyzed aldol-type addition of propargyl alcohols and allenic alcohols to aldehydes (105,106). The products are analogous to Baylis-Hillman reaction adducts (Scheme 16). 

Shibasaki et al. also developed chiral barium catalysts prepared from barium alkoxide and optically active BINOL 3 or aryloxide 4 derivatives. These catalysts were applied to asymmetric Mannich reactions of p,y-unsaturated esters (Table 27) [101]. In this reaction, the initially formed Mannich adducts isomerized to afford aza-Morita-Baylis-Hillman-type products in moderate to good yields with good enantioselectivities. For four substrate examples, ayloxide 4 ligand worked well (entries 2—4). 

The aziridine aldehyde 56 undergoes a facile Baylis-Hillman reaction with methyl or ethyl acrylate, acrylonitrile, methyl vinyl ketone, and vinyl sulfone [60]. The adducts 57 were obtained as mixtures of syn- and anfz-diastereomers. The synthetic utility of the Baylis-Hillman adducts was also investigated. With acetic anhydride in pyridine an SN2 -type substitution of the initially formed allylic acetate by an acetoxy group takes place to give product 58. Nucleophilic reactions of this product with, e. g., morpholine, thiol/Et3N, or sodium azide in DMSO resulted in an apparent displacement of the acetoxy group. Tentatively, this result may be explained by invoking the initial formation of an ionic intermediate 59, which is then followed by the reaction with the nucleophile as shown in Scheme 43. 

Chen and coworkers published a formal [3 + 3]-type reaction to give highly substituted cyclohexenes 8. This domino process consists of an allylic-allylic alkylation of an a,a-dicyanoalkene derived from 1-indanone and Morita-Baylis-Hillman carbonates, following an intramolecular Michael addition, by employing dual orga-nocatalysis of commercially available modified cinchona alkaloid (DHQD)2AQN If (hydroquinidine (anthraquinone-l,4-diyl) diether) and (S)-BINOL. The cyclic adducts... 

The allylic alcohol products from Morita-Baylis-Hillman reactions were shown to participate in a DMAP-mediated Tsuji-Trost-type reaction with /3-diketones or /3-ketoesters, forming the C-allylation product without requiring the use of palladium. Previously, it was shown that allylic alcohols combined with /8-ketoesters and DMAP afforded the transesterification products, in which the allylic alcohol displaced the ester substituent. The difference between these diverging reaction pathways is likely due to the electron-withdrawing group on the allylic alcohol in the MBH adducts vs. just alkyl substituents in the latter case. 

---