Organocatalysts DABCO

It should be noted that catalytic amounts of feA-arylureas and bis-arylthioureas greatly accelerated the DABCO-promoted Baylis-Hillman reaction of aromatic aldehydes with methyl acrylate in the absence of solvent. These robust organocatalysts were better mole-per-mole promoters of the reaction than either methanol or water and they were recovered in higher yields.106... 

Scheme 6.29 Range of products for the DABCO-promoted MBH reaction utilizing urea derivative 16 as hydrogenbonding organocatalyst. The results of the uncatalyzed reference reactions are given in parentheses.

Thiourea catalyst 139 was also screened in the asymmetric Friedel-Crafts reaction between 2-naphthol trans-nitrostyrene (73% yield 0% ee 18 h in toluene at -20 °C and 10 mol%) [277], in the asymmetric aza-Michael reaction of O-benzyl-hydroxylamine to chalcone (72% conv. 19% ee 72 h in toluene at 20 °C and 20mol% catalyst loading) [293], and in the asymmetric Morita-BayUs-HiUman [176, 177] reaction between cyclohexenecarbaldehyde and 2-cyclohexene-l-one (20% yield 31% ee 46 h at rt and 20mol% DABCO and 139) [310]. In aU these transformations, thiourea 139 proved to be not competitive to the organocatalysts probed for these transformations under identical screening conditions and thus was not employed in the optimized protocols. 

A series of A - / - n i trobe nzenesul fony 1 imincs have been reported to undergo asymmetric aza-Morita-Baylis-Hillman reactions with methyl acrylate mediated by DABCO in the presence of chiral thiourea organocatalysts with unprecedented levels of enantioselectivity (87-99% ee), albeit only in modest yields (25 19%). Isolation of a DABCO-acrylate-imine adduct as a key intermediate, kinetic investigation, and isotopic labelling, have been employed to determine the mechanism.177... 

The metal-based Lewis acid derived from the camphor-derived Kgands such as (7.159) and La(OTf)3 is effective in the MBH reaction of aromatic aldehydes with a,P-unsaturated aldehydes mediated by l,4-diazabicyclo(2.2.2]octane (DABCO). The best ees (up to 95%) are obtained using sterically bulky acrylates such as a-naphthyl acrylate. More success has been obtained using Bronsted acidic organocatalysts. The partially reduced BINOL (7.160) has been used to effect enantioselective MBH reaction of aliphatic aldehydes such as (7.71) with 2-cyclohexen-l-one (7.161) mediated by triethylphosphine/ while bis(thio)ureas such as (7.163) provide up to 96% ee in the coupling of this ketone with cyclohex-anecarbaldehyde in the presence of DABCO. °... 

Microwave-assisted DA reactions of substituted 3-acylamino-2H-pyran-2-ones 22 and vinyl-containing dienophiles 23 to give aniline derivatives 24 in 63-74% yield were reported by Kocevar et al. [27]. The reaction was carried out in the presence of l,4-diazabicyclo[2.2.2]octane (DABCO) as an organocatalyst (Scheme 12.8). Alternatively, the reaction could also be performed under high pressure (13-15 kbar) at ambient temperatures in the absence of DABCO as intermediates, 2-oxabicyclo[2.2.2]oct-5-ene 25 and alkoxycyclohexadiene have been isolated to support the proposed mechanism (Scheme 12.9). 

A very similar, though not enantioselective, reaction was reported by Mahdavinia et al. in 2013 [24]. DABCO is used as the organocatalyst in refluxing ethanol for 10-15min, and... 

In 2011, Caddick and co-workers reported a nice asymmetric synthesis of chiral tra s-4,5-dio3grgenated cyclopentenone derivatives based on a sequential organocatalysed rearrangement of pyranones followed by an enzymatic DKR. As shown in Scheme 9.5, the use of DABCO as organocatalyst in combination with lipase AK Amano 20 allowed a series of chiral acetylated cyclopentenones to be achieved from the corresponding pyranones in moderate to high yields and enantioselectivities of up to 96% ee. 

Chiral secondary amines are another important class of privileged functional component in dual organocatalysis that has been widely used in asymmetric catalysis [39]. For example, in 2008, Cordova et al. [40] reported the combinational use of (S)-diphenylprolinol TMS ether (127) and Br0nsted base DABCO (128) as dual organocatalysts to promote the asymmetric domino double Michael addition reaction (nitro-Michael/Michael reaction) of 5-nitropentenoate (125) to a,(i-unsaturated aldehydes (Scheme 43.26), which gave the corresponding nitrogen-,... 

Total synthesis of (—)-nakadomarin A 31, a marine alkaloid of the manzamine family, " was reported by Dixon and co-workers In their synthesis, a bifunctional organocatalyst derived from cinchonidine was effective for the Michael addition reaction of 27 and 28, and stereochemistries at C7 and C8 were efficiently controlled. In this reaction, low selectivity or decomposition of the nitroolefin was observed with the stoichiometric use of lithium 1,1,1,3,3,3-hexamethyIdisiIazide, (or lithium bis(trime-thylsilyl)amide) (LHMDS), potassium 1,1,1,3,3,3-hexam-ethyldisilazide [potassium bis(trimethylsilyl)amide] (KHMDS), or I,4-diazabicycIo[2.2.2]octane (DABCO) (Scheme 27.5). 

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