Hetero-Diels-Alder reaction glyoxylates

Metal-catalyzed asymmetric hetero Diels-Alder reactions of unactivated dienes with glyoxylates 98PAC1117. 

Johannsen M., Yao S., Graven A., Jorgensen K. A. Metal-Catalyzed Asymmetric Hetero-Diels-Alder Reactions of Unactivated Dienes With Glyoxylates Pure Appl. Chem. 1998 70 1117-1122... 

The use of chiral bis(oxazoline) copper catalysts has also been often reported as an efficient and economic way to perform asymmetric hetero-Diels-Alder reactions of carbonyl compounds and imines with conjugated dienes [81], with the main focus on the application of this methodology towards the preparation of biologically valuable synthons [82]. Only some representative examples are listed below. For example, the copper complex 54 (Scheme 26) has been successfully involved in the catalytic hetero Diels-Alder reaction of a substituted cyclohexadiene with ethyl glyoxylate [83], a key step in the total synthesis of (i )-dihydroactinidiolide (Scheme 30). 

Similar transformations have been performed with Danishefsky s diene and glyoxylate esters [85] catalyzed by bis (oxazoHne)-metal complexes to afford the hetero Diels-Alder product in 70% isolated yield and up to 72% ee. Jorgensen [86,87] reported a highly enantioselective, catalytic hetero Diels-Alder reaction of ketones and similar chiral copper(II) complexes leading to enantiomeric excesses up to 99% (Scheme 31, reaction 2). They also described [88] a highly diastereo- and enantioselective catalytic hetero Diels-Alder reaction of /I, y-imsaturated a-ketoesters with electron-rich alkenes... 

Several groups have reported the use of rare earth complexes as catalysts for asymmetric Diels-Alder reaction. Qian and Wang described thus the preparation and use of Yb complexes chelated by Pr-PyBOx to successfully achieve the hetero-Diels-Alder reaction of methyl glyoxylate with Danishefsky s diene in 77% ee and 73% yield (Scheme 37) [98]. 

Bis(trifluoromethanesulfonylamides) ligand was also used by Mikami et al., in 1995, for the lanthanide-catalysed hetero-Diels-Alder reaction of Danishefsky s diene with butyl glyoxylate. This reaction produced the corresponding... 

Li et al.39 reported the hetero Diels-Alder reaction of alkyl-3-(t-butyldimethylsilyl) oxy-1,3-butadiene 95 with ethyl glyoxylate 96 in the presence of a salen-Co(II) catalyst 94 (2 mol%). Product 97 was obtained in 75% isolated yield with an endo. exo ratio >99 1. The enantiomeric excess of the endo-iorm was up to 52% (Scheme 5-30). 

Scheme 23. Copper-catalyzed hetero Diels-Alder reactions of glyoxylates and 1,3-dienes. [Adapted from (226, 227).]...

Whiting and co-workers (231) reported that the chiral diamine 341Cu(OTf)2 complex is moderately effective in inducing the hetero-Diels-Alder reaction between glyoxylate imine (339) and Danishefsky s diene (334). In acetonitrile as solvent, this reaction provides cycloadduct 340 in 58% yield and 86% ee, Eq. 190. 

Jprgensen and co-workers (253) adapted this catalyst system to the hetero-Diels-Alder reaction between Danishefsky s diene and glyoxylate imine. The Tol-BINAP CuC104 proved to be the optimal catalyst for this reaction, affording the... 

The enantiopure complex 35 has since been employed as an atropos asymmetric catalyst for a variety of synthetic transformations (Scheme 8.33)." In addition, the hetero Diels-Alder reaction of glyoxylate could also be catalyzed by enantiopure... 

It has been shown that complete selectivity for the hetero-Diels-Alder cycloadduct 109 (100% endo, 60% ee) can be achieved in the hetero-Diels-Alder reaction of 1,3-cyclohexadiene 108 and ethyl glyoxylate 99 using ent-6 and copper(II) triflate derived catalyst complex. Another interesting reaction introduced by Jprgensen and co-workers was the reaction between 1,3-cyclohexadiene 108 and diethyl ketomalonate 110 to form cycloadduct 111 in 76% yield with an ee of 84% (Fig. 9.35b, p. 558). ... 

Activated dienes such as Danishefsky s diene 112 can also be used in the hetero-Diels-Alder reaction with alkyl glyoxylates. Ghosh and co-workers showed that this reaction proceeded to form cycloadducts 113a,b in yields up to 76% and ee up to 70% using either bu-box 3, phe-box 6 or inda-box ent-9a. The results are summarized in Table 9.18 (Fig. 9.36). 

TABLE 9.18. HETERO-DIELS-ALDER REACTION OE DANISHEFSKY S DIENE WITH GLYOXYLATE ESTERS"... 

TABLE 9.18 HETERO DIELS-ALDER REACTION OF DANISHEFSKY S DIENE WITH GLYOXYLATE ESTERS, 558... 

A similar chiral bis(oxazoline)/Cu(II) catalyst is useful for the asymmetric hetero Diels-Alder reaction of Danishefsky s diene and glyoxylates [63] (Eq. 8A.39). Other bis(oxa-zoline)/M(OTf)2 (M = Sn, Mg) complexes are not effective. This method provides new routes to asymmetric aldol synthesis upon hydrolysis of the resulting adducts. 

In hetero-Diels-Alder reactions, the effect of ligand structure and acidity on the catalytic activity of lanthanide catalysts has been reviewed.191 The effect of different C(2)-symmetric bisoxazolines on the zinc(II)-catalysed hetero-Diels-Alder reaction of ethyl glyoxylate with conjugated 1,3-dienes has been investigated.192 The hetero-Diels-Alder reaction 4-dimethylamino-2-phenyl-l-thiabuta-1,3 -diene with methyl acrylate and /V-cnoyloxazolidinone produces cw-3,4-disubstituted 3,4-dihydro-2//-... 

The choice of solvent has had little, if any, influence on the majority of Diels-Alder reactions.210,211 Although the addition of a Lewis acid might be expected to show more solvent dependence, generally there appears to be little effect on asymmetric induction.118129 However, a dramatic effect of solvent polarity has been observed for chiral metallocene triflate complexes.212 The use of polar solvents, such as nitromethane and nitropropane, leads to a significant improvement in the catalytic properties of a copper Lewis acid complex in the hetero Diels-Alder reaction of glyoxylate esters with dienes.213... 

Lately, also an enantioselective hetero Diels-Alder reaction of a butadiene and glyoxylate in water has been described. The yields and the observed selectivities were higher in water, but the effect was not very pronounced [573],... 

Hetero Diels-Alder Reaction. The hetero-Diels-Alder reaction involving glyoxylate as the dienophile provides an efficient access to the asymmetric synthesis of monosaccharides. The hetero Diels-Alder reaction with methoxydienes proceeds smoothly with catalysis by BINOL-TiCl2 to give the cis product in high enantiomeric excess (eq 14). The dibromide affords a higher cis selectivity, however, with a lower enantioselectivity, particularly in the trans adduct. The product thus obtained can be readily converted to the lactone portion of HMG-CoA inhibitors such as mevinolin or compactin. ... 

Hetero-Diels-Alder Reactions of Aldehydes. Cyclic conjugated dienes, such as 1,3-cyclohexadiene, are excellent substrates for the hetero-Diels-Alder reaction with ethyl glyoxylate catalyzed by Cu[(5, 5 )-t-Bu-box] (OTf)2 (eq 7). The rate of this reaction is dependent on the counterion and the solvent. To obtain... 

The product formed in this hetero-Diels-Alder reaction of ethyl glyoxylate with a cyclic diene catalyzed by (.S, iS )-t-Bu-box in combination with a copper(II) salt was used in the simple synthetic approach to enantiopure synthons for a class of natural products. Saponification of the bicyclic adduct followed by acidification with aqueous HCl provides the enantiopure (>99% ee) rearrangement product (eq 8). ... 

In the course of a formal total synthesis of 3-deoxy-D-maimo-2-octulosonic acid (KDO), a chiral (salen)Co(II) complex was used to catalyze a highly double-stereoselective hetero-Diels-Alder reaction between an electron-rich chiral diene and ethyl glyoxylate (Sch. 56) [201]. This reaction was subsequently extended to achiral dienes [202]. 

We have previously reported that the hetero Diels-Alder reactions of glyoxylates with 1-methoxy-l,3-butadienes proceed smoothly under catalysis by BINOL-Ti complex to give the cis product with high ee (Sch. 48) [128]. The hetero Diels-Alder products thus obtained can be transformed into monosaccharides [129], The hetero Diels-Alder product can, furthermore, readily be converted into the lactone portion of HMG-Co A inhibitors such as mevinolin or compactin [106] in few steps. 

Interestingly, the chiral titanium complex derived from 6-Br-BINOL affords higher cis selectivity, enantioselectivity, and catalytic activity than the parent BINOL-Ti catalyst in the hetero Diels-Alder reactions of 1-methoxydienes with glyoxylate, but not with bromoacrolein (Sch. 49) [130]. 

Hetero-Diels-Alder reactions were performed using, as dienophiles, A -benzyliminoacetyl derivative 586 (R = H, X = NBn) <2001TA1939> and iY-glyoxyl derivative 586 (R= H, X = 0) <2000PAC1589> and cyclic and noncyclic dienes. 

This process (hetero Diels-Alder reaction leading to a dihydropyran system) may be also conducted in an asymmetric version application of chiral transition-metal catalysts based on BINOL, BDMAP, bisoxazolines, etc. provides adducts in very high optical purity (ee up to 99%) [1,6], In a series of papers Jurczak reported recently a highly enantioselective cycloaddition of 1-methoxy-1,3-butadiene and butyl glyoxylate catalyzed with chiral salen complexes [21],... 

Motoyama, Y., Koga, Y., Nishiyama, H. Asymmetric hetero Diels-Alder reaction of Danishefsky s dienes and glyoxylates with chiral bis(oxazolinyl)phenylrhodium(lll) aqua complexes, and its mechanistic studies. Tetrahedron 2001, 57, 853-860. 

Johannsen, M., Yao, S., Graven, A., Jorgensen, K. A. Metal-catalyzed asymmetric hetero-Diels-Alder reactions of unactivated dienes with glyoxylates. PureAppl. Chem. 1998, 70,1117-1122. 

---