Highly diastereoselective Diels-Alder reactions of Baylis-Hillman adducts

[reaction: see text] Baylis-Hillman adducts were found to be excellent dienophiles in Diels-Alder reactions, providing essentially complete diastereocontrol (although mixtures of endo/exo isomers) with all dienes.     

Synthesis of novel tricyclic and tetracyclic sultone scaffolds via intramolecular 1,3-dipolar cycloaddition reactions

The initially prepared 2-formylphenyl-(E)-2-phenylethenesulfonates from the condensation of (E)-2-phenylethenesulfonyl chloride with 2-hydroxybenzaldehyde derivatives underwent intramolecular [3+2] cycloaddition with methyl or phenylhydroxylamine, sarcosine, and l-proline, affording the corresponding novel isoxazolidine, pyrrolidine and pyrrolizidine-annulated γ,δ-benzo-δ-sultones, respectively, in good yields. Unambiguous assignment of the molecular structures was carried out by single-crystal X-ray diffraction.     

First diastereoselective intramolecular Baylis-Hillman reaction: an easy access to chiral alpha-methylene-beta-hydroxylactones

The first diastereoselective intramolecular Baylis-Hillman reaction of chiral substrates is reported wherein both aldehyde and activated olefin coexist as substituents to afford alpha-methylene-beta-hydroxylactones in good yields exclusively as single isomers under the standard base-catalyzed reaction conditions in CH(2)Cl(2). Formation of alkoxylactones by an in situ derivatization of adducts was also observed.     

High diastereoselective synthesis of spiro-isoxazolonechromans via domino oxa-Michael/1,6-addition reactions of ortho-hydroxyphenylsubstituted para-quinone methides with unsaturated isoxazolones

A mild Et₃N-catalyzed novel domino oxa-Michael/1,6-addition reaction of ortho-hydroxyphenylsubstituted p-QMs and unsaturated isoxazolones is described. Various new spiro-isoxazolonechromans were obtained in good yields (up to 89%) with excellent diastereoselectivities (>99:1 dr). The structure of the new compound 3a was determined by single crystal X-ray analysis.     

High diastereoselective synthesis of spiro-barbituratechromans via domino oxa-Michael/1,6-addition reactions of ortho-hydroxyphenylsubstituted para-quinone methides with barbiturate-based olefins

A novel Et₃N-catalyzed domino oxa-Michael/1,6-addition reaction of ortho-hydroxyphenylsubstituted p-QMs with barbiturate-based olefins is achieved under mild conditions. Various new spiro-barbituratechromans were obtained in excellent yields and diastereoselectivities (90–99% yield, >99:1 dr). The structure of the new compound 3a was determined by single crystal X-ray analysis.     

Synthesis of small cyclic peptides via intramolecular Heck reactions

Tripeptides having a 3-bromobenzyl group at the C-termini and an acryloyl group at the N termini undergo efficient intramolecular Heck reactions to afford the corresponding cyclic peptides in good yields. Synthesis of two such peptides is discussed.     

Synthesis of unsaturated seven-membered ring lactams through palladium-catalyzed amination and intramolecular cyclocarbonylation reactions of amines and Baylis-Hillman acetates

A versatile synthesis of unsaturated seven-membered ring lactams has been developed. The sequence involves hydroamination of Baylis-Hillman acetate with amines, followed by intramolecular cyclocarbonylation reactions of the resulting allylamines. This process can tolerate a wide array of functional groups, and affords lactams in excellent yields.     

Synthesis of functionalized quinolines via Ugi and Pd-catalyzed intramolecular arylation reactions

Two types of quinoline scaffolds were constructed in a combinatorial format via the Ugi four-component reaction (U-4CR) and Pd-catalyzed intramolecular arylation reaction. The scope of this two-step synthetic sequence was examined from commercially available and synthetically accessible starting materials.     

Synthesis of bowl-shaped polycyclic aromatic hydrocarbons via palladium-catalyzed intramolecular arylation reactions

[reaction: see text] Treatment of the benzannulated enediyne 11 with potassium tert-butoxide in refluxing toluene for 12 h produced 15 via a cascade sequence of cyclization reactions. Two subsequent palladium-catalyzed intramolecular arylation reactions then afforded the bowl-shaped polycyclic aromatic hydrocarbon 16. The X-ray structures of 16 and two closely related molecules show the presence of significant curvatures.     

Highly diastereoselective synthesis of new indolopyrroloquinolines through intramolecular imino Diels-Alder reactions

A new, efficient and highly diastereoselective one-pot synthesis of cis-fused indolopyrroloquinoline derivatives is described through imino Diels-Alder reaction of substituted anilines or naphthylamines with N-prenylated-2-formyl-3-chloroindoles catalyzed by La(OTf)₃.     

Synthesis of polyketides via diastereoselective acetalization

[reaction: see text] Diastereoselective acetalization of pseudo-C(2)-symmetric 1,3,5-triol systems is a general strategy for the rapid generation of polyketides. The oxidative acetalization reaction shown above was studied under both kinetic and thermodynamic conditions, using synthetic 1,3,5-triol units. In addition, all possible stereochemical variants of a 1,3,5-triol system were prepared from the corresponding acetal to expand the synthetic versatility of this method.     

Synthesis of diverse heterocyclic scaffolds via tandem additions to imine derivatives and ring-forming reactions

A novel strategy has been developed for the efficient syntheses of diverse arrays of heterocyclic compounds. The key elements of the approach comprise a Mannich-type, multicomponent coupling reaction in which functionalized amines, aromatic aldehydes, acylating agents, and π- and organometallic nucleophiles are combined to generate intermediates that are then further transformed into diverse heterocyclic scaffolds via a variety of cyclization manifolds. Significantly, many of these scaffolds bear functionality that may be exploited by further manipulation to create diverse collections of compounds having substructures found in biologically active natural products and clinically useful drugs. The practical utility of this strategy was exemplified by its application to the first, and extraordinarily concise synthesis of the isopavine alkaloid roelactamine.     

Synthesis and selected reactions of a bicyclic sultam having sulfur at the apex position

A practical synthesis of the bicyclic dienyl sultam 9 has been developed. The viable route involved several key steps. Of these, ring-closing metathesis represented by the conversion of 19 to 20 had to be implemented in advance of the assembly of other rings such as is present in 15. Product 20 was used as the template for more advanced framework construction, as in 16. The second double bond was best introduced by a bromination-dehydrobromination sequence, the 2-fold loss of HBr being achieved most reliably by the use of tetra-n-butylammonium fluoride in CH2Cl2 or DMSO. The direct irradiation of 9 gave rise to the endo-oriented cyclobutene derivative 30. The title diene is not a ready participant in Diels-Alder reactions. When heated with endo-bornyltriazolinedione in ethyl acetate solution, conversion to a 1:1 mixture of 33 and its diastereomer occurred as confirmed by X-ray crystallographic analysis. From the mechanistic perspective, this transformation constitutes an interesting example of a stereocontrolled and regioselective [2+2] cycloaddition followed by a vinylcyclobutane-cyclohexene rearrangement. Products 30 and 33 constitute examples of strained sulfonamides featuring a norbornyl-like structural component.     

Highly functionalized dihydrofuran derivatives: Synthesis by diastereoselective intramolecular Wittig reaction

3a,8a‐Dihydroxy‐1,3,3a,8a‐tetrahydro‐ indeno[1,2‐d]imidazole‐2,8‐dione 3 reacts with dialkyl acetylenedicarboxylates in the presence of triphenylphosphine to produce some novel interesting dihydrofuran derivatives diastereoselectively. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:277–279, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20202     

Synthesis and intramolecular reactions of trans-cyclohexyl-1,2-bisacrylate

Photocycloaddition of dimethyl cyclobut-1-ene-1,2-dicarboxylate (1) with cyclohexene (7) afforded two photoadducts 8 and 9 in 44% and 28% yields, respectively. Spontaneous thermal isomerization of 8 gave (4Z,10Z)-dimethyl cyclodeca-4,10-diene-1,4-dicarboxylate (10), which subsequently isomerized to produce trans-1,2-cyclohexanebis-alpha-acrylic acid dimethyl ester 11. Hydride reduction of the bisacrylate 11 gave the trans-octahydro-1H-inden-2-ols 12a and 15 via a novel, stereoselective, intramolecular reaction. Reaction of the bisacrylate 11 with methyllithium afforded the bis-tertiary alcohol 16. In contrast, lithium dimethylcuprate reacted with the bisacrylate 11 to give the trans-hexahydro-1H-inden-2-one 17 in high yield via a novel, stereoselective, intramolecular reaction.     

Synthesis of diazepinones via intramolecular transamidation

[structure: see text] The synthesis of a collection of bicyclic fused azepinones via an intramolecular beta-lactam ring-opening strategy is reported. Depending on the chirality of the various inputs, complete stereocontrol of product formation is achieved.     

Synthesis of cyclopentenones via intramolecular HWE and the palladium-catalyzed reactions of allylic hydroxy phosphonate derivatives

Palladium-catalyzed decarboxylative rearrangement of nonracemic phosphono allylic acetoacetates, or the intermolecular allylic substitution of nonracemic phosphono allylic carbonates with tert-butyl acetoacetate followed by hydrolysis and decarboxylation, gave omega-ketovinyl phosphonates. A highly regioselective Wacker oxidation gave the omega,beta-diketophosphonates which underwent intramolecular HWE reaction to give nonracemic cyclopentenones. An aldol condensation leading to phosphonocyclopentenones was competitive with the HWE reaction. The stereochemistry of the cyclopentenone and the ratio of HWE to aldol products were dependent upon the choice of base used in the reaction.     

The intramolecular Baylis-Hillman reaction: easy preparation of versatile substrates, facile reactions, and synthetic applications

We have developed a general and highly efficient method for the preparation of diverse [small omega]-formyl-[small alpha],[small beta]-unsaturated carbonyl compounds and optimized the conditions for the intramolecular Baylis-Hillman reactions of these compounds to provide various biologically important polycyclic compounds.     

Recent developments in the field of oxa-Michael reactions

Oxa-Michael reactions, i.e. addition reactions of oxygen nucleophiles to conjugated systems, have traditionally received much less attention from the scientific community compared to the addition of carbon nucleophiles to conjugate acceptor systems (Michael reaction). This was mainly due to lack of reactivity and selectivity of these reactions. Within the last few years however, there has been a remarkable increase in publications focussing on method development as well as applications to natural product synthesis. This tutorial review discusses instructive examples that have substantially broadened the scope of oxa-Michael reactions.     

Synthesis of protected chiral vicinal diaminoalcohols by diastereoselective intramolecular benzylic substitution from bistrichloroacetimidates

An efficient synthesis of chiral dihydrooxazines (2) from 1-aryl-2-amino-propane-1,3-diols (1) via the corresponding bistrichloroacetimidate intermediates has been developed. In this transformation, one trichloroacetimidate acts as a leaving group and the other acts as a nucleophile. The cyclization proceeds through an SN1 mechanism to provide trans-dihydrooxazines with complete diastereoselectivity irrespective of the absolute configuration of the benzylic alcohol. The transformation of 2 into other selectively protected aminodiols is also documented. [reaction: see text].