Synthetic application of a substituent controlled claisen rearrangement. Preparation of advanced chiral intermediates for the synthesis of pseudomonic acids

A substituent controlled Claisen rearrangement is employed as the key reaction for a facile construction of chiral intermediates for the synthesis of pseudomonic acids from diacetyl-L-arabinal.     

Compounding Selectivity in Reactions of Diastereoisomeric Radical Intermediates. An experimental demonstration that the yield of a product from a diastereotopic-group-selective reaction can significantly exceed the level of group selectivity

Reduction of a bis-radical precursor, 6-phenyl-1,1-bis[3-(phenylselanyl)propyl]-3a,4-dihydro-1H,3H-cyclopenta[c]furan-5-one ( 6 ), with 3 equiv. of Ph₃SnH provides mixtures of cis,cis- or cis,trans-angular triquinane products (3aα,5aβ,8β,8aR*)- and (3aα,5aα,8β,8aR*)-hexahydro-3a-propyl-8-phenyl-5H-dicyclopenta[b,c]furan-7(8H)-one (cis,cis- 12 /cis,trans- 12 ), in yields that vary from 50%/50% to 91%/6% depending on the reaction concentration. A mechanistic model for this process is proposed that involves a non-selective phenylselenium-group abstraction step followed by successive kinetic resolutions of diastereoisomeric radical intermediates. This reaction shows how yields in group-selective reactions can be compounded to levels above that ostensibly permitted by the level of the group-selective step.     

Polymers for catalytic cation radical chemistry

Cation radical polymers which have cation radical functions at up to 5% of the poly(styrene) monomer sites have been prepared, and their effectiveness in catalyzing the cation radical Diels-Alder reaction is demonstrated.     

Fluorous mixture synthesis of fused-tricyclic hydantoins. Use of a redundant tagging strategy on fluorinated substrates

Simple HPLC experiments were used to identify a redundant tagging scheme wherein six different amino acids were tagged with only four fluorous tags. The tagged amino acids were converted to regiosiomeric mixtures of tricyclic hydantoins. Despite the lack of selectivity, the mixtures were demixed and detagged to give 11 individual pure products in just 25 steps.     

Recent advances in the activation of boron and silicon reagents for stereocontrolled allylation reactions

Despite the popularity of boron and silicon allylation reagents in stereocontrolled synthesis, they suffer from a number of inherent limitations that have slowed down their development as synthetic tools for nucleophilic additions to carbonyl compounds and imine derivatives. These limitations are the low reactivity and diastereoselectivity of allyl trialkylsilane reagents, and the lack of catalytic systems for the activation and substoichiometric control of enantioselectivity in the additions of allyl boron reagents. To develop more efficient and general methods for the control of absolute stereochemistry in the resulting homoallylic alcohols, new approaches aimed at solving the problem of activation of allylic boron and silicon reagents are needed. This Minireview describes a number of recent approaches that have been devised to address this problem.     

Correlation of the rates of solvolysis of benzoyl fluoride and a consideration of leaving-group effects

The specific rates of solvolysis of benzoyl fluoride have been determined at 25.0 degrees C in 37 pure and binary solvents. Together with seven values from the literature, these give a satisfactory correlation over the full range of solvents when the extended Grunwald-Winstein equation is applied. The sensitivities to changes in solvent nucleophilicity and solvent ionizing power are very similar to those for octyl fluoroformate, suggesting that the addition step of an addition-elimination mechanism is rate determining. In the solvent-composition region where benzoyl chloride also shows bimolecular solvolysis, the appreciable k(Cl)/k(F) values are proposed as being primarily due to a more efficient ground-state stabilization for the fluoride.     

A new class of chiral organogermanes derived from C2-symmetric dithiols: synthesis,characterization and stereoselective free radical reactions

A new class of dithiostannanes and dithiogermanes have been prepared from 1,1'-binaphthyl-2,2'-dithiol and 3,3'-bis(trimethylsilyl)-1,1'-binaphtho-2,2'-dithiol. While reduction of 4-butyl-4-chloro-3,5-dithia-4-stanna-cyclohepta[2,1-a;3,4-a']dinaphthalene to the corresponding tin hydride was unsuccessful, 4-tert-butyl-3,5-dithia-4-germa-cyclohepta[2,1-a;3,4-a']dinaphthalene and 4-tert-butyl-2,6-bis(trimethylsilyl)-3,5-dithia-4-germa-cyclohepta[2,1-a;3,4-a']dinaphthalene were obtained by reduction of the parent germanium chlorides with NaBH(4) and LiBH(4), respectively. Kinetic constants for hydrogen transfer to a primary alkyl radical were measured for both germanium hydrides. Reduction of alpha-halo carbonyl compounds by these germanium hydrides occurs with moderate ee values (up to 42%), while hydrogermylation of methyl methacrylate occurs with low selectivity (<3/1) for the former hydride but high selectivity (>10/1) for the latter.     

Comparative Studies of Cathodically-Promoted and Base-Catalyzed Michael Addition Reactions of Levoglucosenone

Regioselective Michael addition of nitro and heterocyclic compounds to levoglucosenone, 1, is effectively catalyzed by amines and also by cathodic electrolysis. In comparison to the base-catalyzed reaction, it was found that under electrochemical conditions the reaction proceeds under milder conditions and with higher yields. Cathodically-initiated Michael addition of thiols to levoglucosenone using small currents produces the previously unknown threo addition product in several instances. The normal erythro isomer, identified as the kinetic product, tends to be formed when large currents are used. In contrast, slow, low current electrolyses promote equilibration of the two forms so that erythro can be converted to threo by the retro reaction and readdition. Addition of 2-naphthalenethiol to (R)-(+)-apoverbenone is also reported.     

Solution-phase preparation of a 560-compound library of individual pure mappicine analogues by fluorous mixture synthesis

Solution-phase mixture synthesis has efficiency advantages and favorable reaction kinetics. Applications of this technique, however, have been discouraged by the difficulty in obtaining individual, pure final products by using conventional separation and identification processes. Introduced here is a new strategy for mixture synthesis that addresses the separation and identification problems. Members of a series of organic substrates are paired with a series of fluorous tags of different chain lengths. The tagged starting materials are then mixed and taken through a multistep reaction process. Fluorous chromatography is used to demix the tagged product mixtures on the basis of the fluorine content of the tags to provide the individual pure components of the mixture, which are detagged to release the final products. The utility of fluorous mixture synthesis is demonstrated by the preparation of a 560-membered library of analogues of the natural product mappicine. A seven-component mixture is carried through a four-step mixture synthesis (two one-pot and two parallel steps) to incorporate two additional points of diversity onto the tetracyclic core. Methods for analysis and purification of the intermediates are established for the quality control of the mixture synthesis.     

Solvolysis-decomposition of 2-adamantyl chloroformate: evidence for two reaction pathways

Reaction of 2-adamantyl chloroformate under a variety of solvolytic conditions leads to 2-adamantyl chloride accompanied by solvolysis products, some with and some without retention of the CO(2) unit. For example, in 100% ethanol, only 4.8% 2-adamantyl chloride is formed with the mixed carbonate (88%) being the dominant product, and in 100% 2,2,2-trifluoroethanol, the products are both formed with loss of CO(2), 59% of the chloride and 41% of the ether. With exclusion of the specific rates in 100% and 90% ethanol and methanol, a good Grunwald-Winstein plot against Y(Cl) values (solvent ionizing power) is obtained, with a slope of 0.47 +/- 0.03. The results are compared with those reported earlier for 1-adamantyl chloroformate and isopropyl chloroformate and mechanistic conclusions are drawn.