Dihydropyranones, from

The Xiao group developed NHC-catalyzed annulations of ynals and enals with 1,3-dicarbonyls, which provide direct and efficient methods for stereoselective synthesis of functionalized dihydropyranones from simple starting materials. The molecular sieves played a crucial role in obtaining excellent yields and selectivity. The mild conditions and high enantiose-lectivity make this approach extremely attractive (up to 90% yield, 98% ee) (Scheme 7.97). 

Further studies by Bode and co-workers have shown that enolate formation from a-chloroaldehydes and subsequent reaction with 4-oxo-enoates or unsaturated a-ketoesters 232 generates dihydropyranones 233 in excellent diastereo- and enantio-selectivities, and with impressively low catalyst loadings [90], This work has been extended to the generation of enolate equivalents from bisulfite adducts of a-haloaldehydes 234 under aqueous conditions (Scheme 12.50) [91]. 

A survey of Wacker-type etherification reactions reveals many reports on the formation of five- and six-membered oxacycles using various internal oxygen nucleophiles. For example, phenols401,402 and aliphatic alcohols401,403-406 have been shown to be competent nucleophiles in Pd-catalyzed 6- TZ /fl-cyclization reactions that afford chromenes (Equation (109)) and dihydropyranones (Equation (110)). Also effective is the carbonyl oxygen or enol of a 1,3-diketone (Equation (111)).407 In this case, the initially formed exo-alkene is isomerized to a furan product. A similar 5-m -cyclization has been reported using an Ru(n) catalyst derived in situ from the oxidative addition of Ru3(CO)i2... 

Scheme 12.23 Danishefsky transformation dihydropyranone product Pj obtained from Pi after acidic work-up with trifluoroacetic acid (TFA).

Another general approach to sugars starts from (2-furyl)methanols (furfuryl alcohols, 22). Bromination at low temperature in methanol (Clauson-Kaas reaction) and subsequent mild acidic hydrolysis of 2,5-dimethoxy-2,5-dihydrofurans 23 obtained, leads to 6-hydroxy-2,3-dihydro-6//-pyran-3-ones 24 (Scheme 8) [40], The same dihydropyranones can be... 

Cyclocurcumin differs from curcumin in the p-diketone link. In this molecule, the a, p-unsaturated p-diketone moiety of curcumin is replaced by a, p-unsaturated dihydropyranone moiety. Up to now, not many biological studies are reported with cyclocurcumin except for one study on inhibition of MCF-7 tumor cell proliferation by Simon et al. [1998] where it has been found to be ineffective in inhibiting cell proliferation and arrest of cell-cycle progression. 

The polymer-bound Mn and Cr complexes were used as catalysts for epoxidations of six phenyl-substituted olefins with m-CPBA/NMO and for dihydropyranone formation from the Danishefsky diene and aldehydes. There are several remarkable features of the novel immobilized salens ... 

The synthesis of 1,5-diketones 521 from 3,4-dihydropyranones 519 has been reported and is shown in Scheme 95 <1999T9333>. Organolithium reagents were used to open the lactone reagents, and best results were achieved when the reactions were quenched with trimethylsilyl chloride prior to hydrolytic workup. 

Elimination of the sulfone from the tetrahydropyran-2-one 661 occurs with a concomitant shift of the exocyclic methylene bond to afford the meta-bridged 277-pyran-2-one 662 (Equation 268) <1999JOC8281>. The addition of bromine to dihydropyranones and elimination of 2 equiv of HBr yields 277-pyran-2-ones < 1984CHEC, 1996CHEC-II>. 

From a preformed heterocyclic ring 7.08.24.1.4 From dihydropyranones... 

With inexpensive hydroxy acids as chiral tethers, only two stereochemic pure head-to-head 118 and head-to-tail 119 cycloadducts were isolated from lactate 117. With the corresponding dihydropyranone 120, the facial select decreased and head-to-head cycloadducts were obtained as a mixture of t diastereoisomers 121 and 122 (Scheme 27). I... 

The origin of dihydropyran 123 can be traced to the known dihydropyranone 124, derived from commercially available acetylacetaldehyde dimethylacetal 125. Although the oxygen at C4 of dihydropyran 123 is not present in the natural product, its role was to facilitate a stereocontrolled epoxidation reaction as well as the stereoselective formation of the Q-C-glycoside. Its presence also... 

Cyclobutane.—Further reports of grandisol (90) synthesis include Magnus s full paper (Vol. 6, p. 22) and an almost identical Japanese report of an earlier synthesis (Vol. 3, p. 25) based upon a dihydropyranone-ethylene cycloaddition.A third synthesis utilizes cyclopropanation of 4-methoxy-3,6,6-trimethylcyclohexa-2,4-dienone to yield (91) followed by rearrangement of the a-oxycyclopropylcarbinyl cation of (91) to (92). After reduction of the cyclobutanone, second-order Beckmann cleavage of the cyclopentanone oxime gave (93) from which grandisol (90) was readily obtained. 

Chapter 4 tells of a successful program in which potent non-peptide inhibitors of HIV protease from the AIDS virus were developed. Cou-marins and dihydropyranones were identified as viable chemical leads via screening. Rational drug design, aided by molecular modeling and X-ray crystal analysis, along with the development of sound structure-activity relationships, yielded a number of promising clinical candidates. 

Acetylketene [4 + 2] cycloaddition with vinyl n-butyl ether gave the useful dihydropyranone intermediate (32), from which various 2,6-dideoxy monosaccharides were obtained. The key steps in synthesis of racemic butyl olivoside (34) consisted of stereoselective 1,2-reduction of conjugated ketone with diisobutylaluminum hydride, followed by standard hyrobora-tion/oxidation procedure (Scheme 3) [53]. 

The Biju group discovered an NHC-catalyzed generation of chiral a,p-unsaturated acylazoliums from 2-bromoenals followed by their interception with 1,3-dicarbonyl compounds or enamines, via a formal [3 + 3] annulation reaction. The reaction results in the enantioselective synthesis of synthetically and medicinally important dihydropyranones and dihydropyridinones, and tolerates a wide range of functional groups. It is noteworthy that the... 

---