A-Acyloxyacrolein

Ishihara and Nakano reported a complex triamine catalyst which was effective for the enantioselective Diels-Alder reaction of a-acyloxyacroleins [190]. They have subsequently described binaphthyl catalyst 142 which gave higher yields and enan-tioselectivities within the same transformation [191, 192]. Reaction of a range of dienes and a-acyloxyacroleins in the presence of 142 (10 mol%) and... 

Scheme 56 Diels-Alder reaction of a-acyloxyacroleins catalysed by binaphthylamine 142...

Ishihara has reported an unusual enantioselective [2h-2] cycloaddition of unactivated alkenes with a-acyloxyacroleins catalysed by triamine 150 [203]. Although the precise mechanistic details of this transformation are unclear at present, a possible... 

General Procedure for Asymmetric Cycloaddition of Dienes with a-Acyloxyacroleins [85] (p. 100)... 

Sakakura A, Suzuki K, Nakano K, Ishihara K (2006) Chiral l,l -binaphthyl-2,2 -diammonium salt catalysts for the enantioselective Diels-Alder reaction with a-acyloxyacroleins. Org Lett 8 2229-2232 Sanwal BD, Zink MW (1961) L-Leucine dehydrogenase of Bacillus cereus. Arch Biochem Biophys 94 430-435... 

Ishihara, et al. reported an organocatalytic enantioselective Diels-Alder reaction of dienes a-(A,iV-diacylamino)acroleins, Scheme 3.44 [59], DFT calculation (with B3LYP) of catalyst revealed that the (Z)-aldiminium salt derived from a-(N,N-diacylamino)acrolein and catalyst has 2.8 kcal/mol lower energy than the fi-form conformer. Based on this fact, diene should approach enantiomerically the Si face of the electron-deficient enimide to give the ent/<9-(25)-adduct as a major product. Earlier, catalyst 134-Tf2NH as well as l,l -binaphthyl-2,-2 -diammonium salt (catalyst-TfjNH) were used in the enantioselective Diels-Alder reaction with a-acyloxyacroleins [60]. 

Ishihara, K. et al. reported an enantioselective [2+2] cycloaddition of unactivated alkenes (e.g., 161) with a-acyloxyacroleins 162, catalyzed by chiral organoammo-nium salts, catalyst 163, Scheme 3.52 [68], A possible stepwise mechanism was proposed by authors to account for the stereoselectivity, which includes initial Michael addition of alkene to (Z)-iminium enal intermediate and intramolecular cyclization to afford the cycloadducts. The proposed transition states were stabilized by aromatic n-n stacking and intramolecular hydrogen-bonding interaction. 

Scheme 3.52 Oiganocatalytic enantioselective [2 + 2] cycloaddition of 1,3,3-trimethylcyclohex-1-ene 161 and a-acyloxyacroleins...

SCHEME 6.26. Formal [2+2] cycloaddition of unactivated alkenes with a-acyloxyacroleins... 

The formal [2+2] cycloaddition also provides an interesting approach for stereoselective synthesis of chiral cyclobutane derivatives. Ishihara and co-workers [70] reported the enantioselective [2 + 2] cycloaddition of unactivated alkenes 113 with a-acyloxyacroleins (Scheme 6.26). The reaction is catalyzed by chiral anunonium salt 114 and gives highly functionalized cyclobuten derivatives 115 with high... 

Three- and four-membered rings are versatile intermediates for further transformation. Tsutomu Katsuki of Kyushu University developed Angew. Chem. Int. Ed. 2008, 47, 2450) an elegant Al(salalen) catalyst for the enantioselective Simmons-Smith cyclopropanation of allylic alcohols such as 3. Kazuaki Ishihara of Nagoya University found J. Am. Chem. Soc. 2007,129, 8930) chiral amine salts that effected enantioselective 2-1-2 cycloaddition of a-acyloxyacroleins such as 5 to alkenes to give the cyclobutane 7 with high enantio- and diastereocontrol. 

Ishihara has designed dipeptide-derived triamine catalyst 20 and elegantly demonstrated its value in a Diels-Alder reaction [57]. The primary amine group, in combination with an acid co-catalyst, facilitated the activation of a-acyloxyacrolein in the Diels-Alder reactions, and the adducts were obtained in good yields and with good to excellent enantioselectivities (Scheme 3.21). 

In comparison with the widespread application of chiral secondary amines in organocatalytic Diels-Alder reactions, only a few successful examples have been reported with the use of chiral primary amines. In the case of a-substituted acroleins, it is difficult for chiral secondary amines to activate this type of substrates, probably because of poor generation of the corresponding iminium ions. To solve this problem, Ishihara and Nakano designed and synthesized a novel class of primary amine catalysts (55) [24]. Indeed, this type of less bulky ligand proved to be effective for enantioselective Diels-Alder reactions of a-acyloxyacroleins 51 or a-phthalimidoacroleins 53 to produce the desired cycloadducts 52 or 54 with quaternary stereocenters (Scheme 38.16). 

A diammonium salt of chiral l,r-binaphthyl-2,2 -diamine and trifluoromethane-sulfonimide (Tf NH) (5mol% loading) showed excellent catalytic activity and enantioselectivity (88% yield with 92% exo and 91% ee) toward the Diels-Alder reaction of a-acyloxyacroleins with cyclic dienes [69]. Extension of Diels-Alder reactions to a-branched aldehydes was also reported [70]. 

In 2006, Ishihara showed that a diammonium salt of commercially available chiral (S)-2,2 -diamino-l,T-binaphthalene (20) and bis(trifluoromethane)sulfon-imide (Tf2NH) exhibited excellent catalytic activity and stereoselectivity in the Diels-Alder reaction of a-acyloxyacroleins with cychc dienes (Scheme 7.33) [57]. 

The first iminium-based asymmetric Diels-Alder reaction of a-acyloxyacrolein was realized by using a primary amine catalyst 128 derived from amino acids [62a]. The same catalyst could also be appUed to the Diels-Alder reactions of a-phthalim-idoacroleins with dienes [62b] with up to 99 1 cndo cjt -selectivity and 96% ee (Scheme 5.33). Two factors are proposed to account for the high stereocontrol n-n interaction between the phenyl group of the catalyst and the R group in the acroleins and the steric hindrance resulted from the bulky ion pair (Schane 5.33). 

Axially chiral diamine 132 in combination with Tf NH has also been reported to promote the asymmetric Diels-Alder reaction of a-acyloxyacroleins [63]. Improvements on stereoselectivity were observed in the reactions with cyclopenta-diene over those in catalysis with 128 (Scheme 5.34). With a more advanced analogue of 132, i.e. diamine 134, Maruoka reported highly enantioselective Diels-Alder reactions with a-alkyl substituted acroleins (Scheme 5.35) [64]. 

Using their previously developed triamine catalyst 128, Ishihara and coworkers reported an unprecedented [2+2] cycloaddition between a-acyloxyacroleins and tris-substituted alkenes (Scheme 5.37) [66]. Presumably, the reaction occurs via stepwise Michael addition and type cyclization. A similar transition state as in the Diels-Alder reaction (Scheme 5.33) was proposed to account for the observed stereoselectivity. 

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