Enantioselectivity conjugated diene reactions

This chapter will focus on the development of catalytic enantioselective cycloaddition reactions of carbonyl compounds with conjugated dienes (Scheme 4.1) [3]. 

The catalytic enantioselective cycloaddition reaction of carbonyl compounds with conjugated dienes has been in intensive development in recent years with the main focus on synthetic aspects the number of mechanistic studies has been limited. This chapter will focus on the development and understanding of cycloaddition reactions of carbonyl compounds with chiral Lewis acid catalysts for the preparation of optically active six-membered ring systems. 

The major developments of catalytic enantioselective cycloaddition reactions of carbonyl compounds with conjugated dienes have been presented. A variety of chiral catalysts is available for the different types of carbonyl compound. For unactivated aldehydes chiral catalysts such as BINOL-aluminum(III), BINOL-tita-nium(IV), acyloxylborane(III), and tridentate Schiff base chromium(III) complexes can catalyze highly diastereo- and enantioselective cycloaddition reactions. The mechanism of these reactions can be a stepwise pathway via a Mukaiyama aldol intermediate or a concerted mechanism. For a-dicarbonyl compounds, which can coordinate to the chiral catalyst in a bidentate fashion, the chiral BOX-copper(II)... 

Scheme 2.5) was recently reported by Komatsu, Minakata, and coworkers [12]. The reaction with the (i ,i )-complex 12 provided the first reagent-controlled asymmetric aziridination of conjugated dienes, although enantioselectivities were only low to moderate (20-40% ee). 

Burgess and coworkers investigated the hydrogenation of the conjugated diene 87 (Scheme 30.1) [48]. Kinetic studies showed that the reaction occurred mostly stepwise via 2,3-diphenyl-l-butene, while only a small part of the diene was converted directly to 2,3-diphenylbutane, without dissociation of the catalyst from the intermediate mono-alkene. The first hydrogenation step was found to proceed with low enantioselectivity, whereas the second step was characterized by strong catalyst and strong substrate control. 

The axially chiral (allenylmethyl) silanes 110 were also prepared in optically active form using chiral Pd catalysts [98]. For the asymmetric synthesis of 110, a Pd/(R)-segphos system was much better in terms of enantioselectivity than the Pd/(R)-binap catalyst. Under the optimized conditions, 110m and llOt were obtained in 79% ee (57% yield) and 87% ee (63% yield), respectively (Scheme 3.56). The enantio-merically enriched (allenylmethyl) silanes 110 served for Lewis acid-promoted SE reaction with tBuCH(OMe)2 to give conjugated dienes 111 with a newly formed chiral carbon center (Scheme 3.56). During the SE reaction, the allenic axial chirality was transferred to the carbon central chirality with up to 88% transfer efficiency. 

Dioximato-cobalt(II) catalysts are unusual in their ability to catalyze cyclopropanation reactions that occur with conjugated olefins (e.g., styrene, 1,3-butadiene, and 1-phenyl-1,3-butadiene) and, also, certain a, 3-unsaturated esters (e.g., methyl a-phenylacrylate, Eq. 5.13), but not with simple olefins and vinyl ethers. In this regard they do not behave like metal carbenes formed with Cu or Rh catalysts that are characteristically electrophilic in their reactions towards alkenes (vinyl ethers > dienes > simple olefins a,p-unsaturated esters) [7], and this divergence has not been adequately explained. However, despite their ability to attain high enantioselectivities in cyclopropanation reactions with ethyl diazoacetate and other diazo esters, no additional details concerning these Co(II) catalysts have been published since the initial reports by Nakamura and Otsuka. 

In contrast to olefins, little is known on catalytic hydroboration of conjugated dienes. Suzuki and Miyaura20 described a 1,4-addition of catecholborane to acyclic 1,3-dienes, catalyzed with tetrakis(triphenylphosphine)pa]ladium(0). An interesting Markovnikov type regioselectivity was observed in the enantioselective dihydroboration of (E)-1-phenyl-1,3-butadiene with catecholborane, catalyzed by chiral rhodium complexes.21 However, the scope of these reactions is not well known, and the choice of catalysts is very limited. 

Conjugated dienes can be regioselectively cyclopropanated at the terminal double bond with excellent chemoselectivity to produce the corresponding vinylcyclopropanes 27 and 28 in 86% yield and with a moderate diastereomeric ratio, Eq. (8). The enantioselectivity for the trans isomer 27 was excellent. On the other hand, P-methylstyrene, 2,5-dimethyl-2,4-hexadiene, cyclopentene, and indene could not be cyclopropanated under the same reaction conditions. 

Double AD of dienes is an interesting way to enhance the enantioselectivity of the first dihydroxylation reaction. This amplification process, which has been applied to many other asymmetric reactions, usually results in significant improvement of the enantiopurity of the bis dihydroxylated product. Momose [ 140] has studied in detail the double AD of several non-conjugated dienes, during his elegant synthesis of a range of optically active nitrogen heterocycles (Scheme 62). 

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