Application to the Synthesis of Natural Products

Streith J., Defoin A. Hetero Diels-Alder Reactions With Nitroso Dienophiles Application to the Synthesis of Natural Product Derivatives Synthesis 1994 1107-1117 Keywords chiral dienes, chiral nitroso dienophiles... 

Keywords stereochemistry, applications to the synthesis of natural products... 

Recently, the first examples of catalytic enantioselective preparations of chiral a-substituted allylic boronates have appeared. Cyclic dihydropyranylboronate 76 (Fig. 6) is prepared in very high enantiomeric purity by an inverse electron-demand hetero-Diels-Alder reaction between 3-boronoacrolein pinacolate (87) and ethyl vinyl ether catalyzed by chiral Cr(lll) complex 88 (Eq. 64). The resulting boronate 76 adds stereoselectively to aldehydes to give 2-hydroxyalkyl dihydropyran products 90 in a one-pot process.The diastereoselectiv-ity of the addition is explained by invoking transition structure 89. Key to this process is the fact that the possible self-allylboration between 76 and 87 does not take place at room temperature. Several applications of this three-component reaction to the synthesis of complex natural products have been described (see section on Applications to the Synthesis of Natural Products ). 

APPLICATIONS TO THE SYNTHESIS OF NATURAL PRODUCTS Enantioselective Additions... 

Barone, R. and Channon, M. (2001) A new and simple approach to chemical complexity. Application to the synthesis of natural products. JCICS 41, 269-272. 

The Pd-catalyzed acylation of organozincs was reported in 1983144, and it has since been widely employed as one of the most satisfactory methods of acylation of organometals20. Even in cases where ,/J-unsaturated carbonyl compounds are the products, their subsequent conjugate addition reactions do not appear to be competitive. Among recent examples of its application to the synthesis of natural products, the synthesis of amphidi-nolides Tl, , T4 and T5 by Fiirstner and coworkers213 is particularly noteworthy (Scheme 81). 

J. M. Hook, L. N. Mander, Recent Developments in the Birch Reduction of Aromatic Compounds Applications to the Synthesis of Natural Products , Nat. Prod. Rep. 1986, 3, 35. 

The inter- and intramolecular Diels-Alder reactions of furans, and their applications to the synthesis of natural products as well as synthetic materials, were reviewed <1997T14179>. HfCU promoted the endo-seXccuve. inter-molecular Diels-Alder cycloadditions of furans with a,/3-unsaturated esters <2002AGE4079>. The cycloaddition between furan and methacrylate was also achieved under these conditions, providing, however the o-isomer as the major cycloadduct. A catalytic enantioselective Diels-Alder reaction between furan and acryloyl oxazolidinone to provide the < 46i-adduct in 97% ee was achieved by using the cationic bis(4-fer7-butyloxazoline)copper(ll) complex 55, as shown in Equation (41) <1997TL57>. 

On the basis of the work summarized above, it would appear that the Cope rearrangement of 6-(l-alke-nyl)bicyclo[3.1.0]hex-2-enes should be usefully applicable to the synthesis of natural products that possess, as part of their structures, the bicyclo[3.2.1]octane carbon skeleton. Recent work in this area. 

For the chosen examples, the, inevitably subjective, emphasis was laid preferentially on the synthetic use of the presented reactions and on their applicability to the synthesis of natural products or other important molecules which prove difficult to synthesize, rather than on mechanistic or theoretical aspects, unless these are essential for the prediction of the chemo-, regio- or stereo-selective outcome of the reaction. 

Streith, J., Defoin, A. Hetero Diels-Alder reactions with nitroso dienophiles application to the synthesis of natural product derivatives. Synthesis 1994,1107-1117. 

In this review, methods for the construction of oxabicyclic substrates of general structure 1, Fig. 1, are described as well as ring opening reactions which are applicable to the synthesis of natural products. 

Bromination reactions of the endocyclic double bond in 2-substituted 7-oxabicyclo[2.2.1]hept-5-ene with bromine gives tram- and civ-productsl44. These and other bicyclic products144 attract a great deal of attention due to their applicability to the synthesis of natural products. 

For a brief review of the Birch reduction and its application to the synthesis of natural products, see Schultz, A.G. 

Benzo[c]furans , Friedrichsen, W., Adv. Heterocycl. Chew., 1980, 26, 135 Isobenzo-furan , Haddadin, M. J., Heterocycles, 1978, 9, 865 Progress in the chemistry of isobenzofurans applications to the synthesis of natural products and polyaromatic hydrocarbons , Rodrigo, R., Tetrahedron, 1988, 44, 2093 Recent advanees in the chemistry of benzo[c]furans and related compounds , Friedrichsen, W., Adv. Heterocycl. Chew., 1999, 73, 1. 

Many examples of guanidine base-promoted nitro aldol reactions [1] and their application to the synthesis of natural products have been reported. Ishikawa et al. synthesized (- -)-cyclophelhtol (14), an a-glucosidase inhibitor and also a potential inhibitor of HIV, via the intramolecular 1,3-dipolar cycloaddition reaction of silylnitronate 13. In this synthesis, nitroalcohol 12 was prepared by the reaction of aldehyde 11 with nitromethane in the presence of TMG (3) as a 2 1 diastereomeric mixture [2] (Scheme 7.1). 

The sulfur version of the Claisen rearrangement has emerged as a facile route towards the formation of C-C bonds and as an attractive synthesis of thiocarbonyl compounds. It was performed with successful control of both relative and absolute configurations and provides access to a variety of sulfur heterocycles. Relatively few applications to the synthesis of natural products have been reported so far, but they illustrate the advantages of the sulfur version. 

Application to the Synthesis of Natural Products and Chiral Auxiliaries... 

A review of cycloaddition reactions in carbohydrate chemistry is presented. The use of carbohydrate-derived dienes and dienophiles in the Diels-Alder reaction, hetero-Diels-Alder and dipolar addition reactions of carbohydrates are described. Stereochemical aspects of the cycloaddition processes are also discussed, and applications to the synthesis of natural products are included for each reaction type. Much of the material presented has appeared in the literature within the past five years however, earlier studies are also included in order to give a more representative historical perspective. 

---