Monosaccharides Diels-Alder reaction

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. ... 

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. 

Dihydropyrans are useful intermediates in the total synthesis of monosaccharides and have been prepared by hetero-Diels-Alder reaction of simple alkyl- and arylaldehydes 48 with electron-rich ( )-l-methoxy-l,3-butadiene (49) in reasonable to good yield. As expected e do-diastereoselectivity is predominant because, as usual, pressure strongly favours e do-addition (Scheme 7.12). 

As illustrated in the previous two examples, the hetero Diels-Alder reaction provides a useful entry into the preparation of C-monosaccharides. However, as illustrated in Scheme 7.5.4, Danieshefsky, etal.,2728 utilized this methodology in the preparation of a C-linked disaccharide. As shown, the aldehyde produced from a galactose derivative was reacted with a diene under chelation control. The ultimate result was a single isomer of a C-glycoside containing extremely versatile functionalities. 

Diels-Alder methodology is well suited to the preparation of C-monosaccharides and higher carbohydrate analogs. In general, these reactions provide products with high degrees of stereochemical induction as well as exhibiting synthetically useful yields. Further examples of Diels-Alder reactions applied to the preparation of C-disaccharides will be elaborated upon in Chapter 8. 

An important development in the hetero Diels-Alder reaction came when Jurczak used high pressure to help improve the reactivity of dienes with aldehydes. 1-Methoxybutadiene, for example, was shown to react at 15-25 kbar (I bar = l(X) kPa) with a variety of unactivated aldehydes. - These reactions give predominantly endo adducts and allow for the use of simple alkyl and aromatic aldehydes as dienophiles. Jurczak also realized the importance of this reaction in the synthesis of carbohydrates and applied it to the construction of simple monosaccharide derivatives (see Section 2.5.2. ). " ... 

The Danishefsky group has extensively applied this methodology to total synthesis of a number of natural products.45 In particular, the method has provided entry to several types of carbohydrate, both simple and complex. For example, the monosaccharide L-talose could be prepared in just a few steps using a hetero Diels-Alder reaction [Eq. (15)].44 ... 

Chiral thiopyran derivatives have been obtained in Diels-Alder reactions from monosaccharide O-thioformates and dithiooxalates. Intramolecular Diels-Alder cyclization of 1,6,8-nonatrienes and 1,7,9-decatrienes prepared from pentoses or D-glucose afforded multichiral hexahydroindene and octahydronaphthalene derivatives with very high diastereoselectivity. 

Intramolecular Diels-Alder (IMDA) reactions of 1,6,8-nonatrienes and 1,7,9-decatrienes have been used frequently for the construction of chiral ring systems of complex natural products (18-20), Although saccharide derivatives have been employed many times in intermolecular Diels-Alder reactions (21-28) their IMDA reaction appears not to have been studied so far. The diastereoselectivity of IMDA reactions can be influenced, among other factors, by the size of substituents, and by the chirality of carbons of the connecting chain. Our aim was to study the possibilities of the application of single monosaccharides as tether chains in IMDA reactions. The influence of the presence of three or four chiral... 

The diol 4 had never been described in the literature before we used it in the synthesis of 1. Initially, we tried to synthesize it using an enantioselective Diels-Alder reaction between a chiral fumarate equivalent 5 (Scheme 10.1) and butadiene 6, followed by double-bond dihydroxylation [41]. However, a more effective protocol for large-scale synthesis could finally be based on the procedure shown in Scheme 10.2, leading to enantiomericaUy pure (lS,2S)-cyclohex-4-ene-1,2-dicarboxylic acid 7 [42]. Here, a Bolm desymmetrization of tetrahydrophthahc anhydride 8 using quinine leads to monoester 9 in 89% ee. The monoester 9, in turn, can be epimerized to the trans isomer 10 which is hydrolyzed to obtain 7, after crystallization. This intermediate is the starting material for the synthesis of 4 and of other conformationally constrained DCCHD to be used as monosaccharide mimics [43, 44]. Our current best protocol for the large-scale synthesis of 7 is reported at the end of this chapter. 

Several novel monosaccharide derivatives containing a sulphur atom in the ring have been obtained via Diels-Alder reactions of methyl cyanodithioformate with buta-1,3-diene (197) and /m/7J-l-methoxybuta-l,3-diene (198) (Scheme 73) the... 

Thioaldehyde was also used as dienophile affording corresponding dihydro-2H-thiopyrans P. Herczegh, M. Zsely, R. Bognar, S. Laszlo, Cycloaddition reactions leading to carbohydrate derivatives part I. Hetero Diels-Alder reaction of monosaccharide O-thioformates, Tetrahedron Lett. 27 (1986) 1509-1512. 

The hetero-Diels-Alder cyclization reaction of tra s-l-methoxy-3-trimethylsilyloxy-1,3-butadiene (Si) (= Danishefsky s diene) with benzaldehyde (S ) (Scheme 12.23) [217-221] is a promising reaction for evaluating the catalytic properties of Lewis acidic lanthanide centers, and has enormous potential for asymmetric synthesis of natural products (e.g., monosaccharides) [222-225]. 

Considerable effort has heen directed towards the synthesis of monosaccharide derivatives, and, in particular, C-glycosyl compounds, from Diels-Alder adducts offuran. Just and his group investigated the reaction of furan with a number of dienophiles, and described many interesting transformations of the adducts obtained from... 

Much of the early scientific work of the late Aleksander Zamojski focused on the total synthesis of racemic monosaccharides, based on stereocontrolled reactions of substituted dihydropyrans obtained by Diels—Alder cycloaddition. His article in Volume 40 of this series details many of his early studies in this area. His colleagues Jarosz and Chmielewski (Warsaw) here offer a broad insight into Zamojski s contributions, which later extended into chiral structures, higher sugars, and oligosaccharides. 

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