Access to [6.4.0]carbocyclic systems by tandem metathesis of dienynes. A step toward the synthesis of a PreD3-D3 transition state analogue

[reaction: see text] A new approach to the synthesis of linearly fused 6-8-6 tricarbocyclic systems, tandem ring-closing metathesis of dienynes, allows access to compounds with a carbon framework analogous to the proposed transition state of the isomerization of previtamin D(3) to vitamin D(3).     

RCM for the construction of novel steroid-like polycyclic systems. 1. Studies on the synthesis of a PreD3-D3 transition state analogue

Natural and nonnatural polycyclic systems containing eight-membered carbocycles constitute a large class of compounds of importance in organic chemistry, biology, and medicine. Here we describe a new strategy by which complex polycyclic steroid-like systems can be constructed on the steroid CD framework, by a combination of RCM and Heck cyclizations. The method is exemplified by its application to the stereoselective synthesis of 6-8-6 fused carbocyclic systems that mimic the putative transition structure of the isomerization of previtamin D3 to vitamin D3.     

An application of the ireland reaction to the stereospecific synthesis of fused carbocyclic systems.

The sequence: group transfer Michael addition, aldol / lactonization and Claisen rearrangement provides access to the title compounds.     

Tandem aza-Claisen rearrangement and ring-closing metathesis reactions: the stereoselective synthesis of functionalised carbocyclic amides

A one-pot, tandem process has been developed for the efficient synthesis of functionalised carbocyclic amides. A substituted cyclopentenyl trichloroacetamide was synthesised using a tandem thermal aza-Claisen rearrangement and RCM process, while an analogous cyclohexenyl trichloroacetamide was generated with high diastereoselectivity using a tandem MOM-ether directed metal-catalysed aza-Claisen rearrangement and RCM process.     

[6+3] Cycloaddition of pentafulvenes with 3-oxidopyrylium betaine: a novel methodology toward the synthesis of 5-8 fused oxabridged cyclooctanoids

Pentafulvenes undergo a facile [6+3] cycloaddition with 3-oxidopyrylium betaine, generated from the corresponding pyranulose acetate, leading to the formation of 5-8 fused oxabridged cyclooctanoids. The product is formed by a [6+3] cycloaddition, followed by a 1,5-hydrogen shift of the initially formed [6+3] adduct. The reaction was found to be general and a number of fulvenes with a wide range of substituents at the exocyclic double bond, that is, at the C6 position followed a similar reactivity pattern. The [6+3] adduct, a 5-8 fused oxabridged cyclooctanoid, is potentially amenable to a number of synthetic transformations due to the presence of an α,β-unsaturated ketone and cyclopentadiene part. By selecting appropriately substituted fulvene and pyranulose acetates, it is possible to use this methodology for the synthesis of a wide range of 5-8 fused cyclooctanoids. The experimental results have been rationalized on the basis of theoretical calculations.     

Towards the synthesis of massadine: a unified strategy for the stereoselective synthesis of the carbocyclic C,D-ring subunit

Massadine is a hexacyclic marine natural product, which belongs to the family of pyrrole-imidazole alkaloids. Herein, we describe a unified approach to the C,D-ring subunit of this sponge metabolite based on the exploitation of a norbornene scaffold for the stereocontrolled construction of massadine's carbon skeleton. Highlights of the sequence presented include the application of a stereospecific norbornyl rearrangement for facile introduction of an oxygen at the C7-position within the norbornene nucleus, a highly regioselective and end group differentiating ozonolytic scission of a C-C double bond, and an oxidative decarboxylation reaction for the installation of the hindered secondary C2-alcohol function. Furthermore, the iterative assembly of the two guanidine entities as well as the implementation of the spirocyclic junction between the C- and the D-rings are described. Collectively, these key transformations permit an entry to an appropriately functionalized carbon framework, which will serve as a starting point for our efforts toward the completion of the synthesis of massadine.     

Regio- and stereoselective synthesis of the carbocyclic analogue of 3-deoxy-β-D-manno-2-octulopyranosonic acid (β-KDO) from (-)-quinic acid.

The carbocyclic analogue of β-KDO has been synthesized from (-)-quinic acid.     

Toward the synthesis of norzoanthamine: building carbocyclic core by a transannular Michael reaction cascade

A 12-step synthesis of the ABC carbocyclic core of norzoanthamine is described. It features an organocatalytic asymmetric intramolecular aldolization to set the stereochemistry of the entire molecule, a fragment coupling by selective alkylation of a bis-enolate, and a transannular Michael reaction cascade for rapid and stereoselective synthesis of the polycyclic core.     

Toward the total synthesis of natural peloruside a: stereoselective synthesis of the backbone of the core

[reaction: see text] An asymmetric synthesis of the backbone of the core of natural peloruside A is described. Key elements include reiterative application of enantioselective allylation to establish the stereochemistry of the backbone and a double asymmetric aldol reaction to successfully couple two fragments.     

Toward the total synthesis of tetrodotoxin: stereoselective construction of the 7-oxanorbornane intermediate

The stereoselective synthesis of 7-oxanorbornane regarding as a key synthetic intermediate of tetrodotoxin (TTX) is reported. The bicyclo ring bearing various functional groups was successfully elaborated by a furan Diels–Alder (DA) reaction. The stereoselective installation of a quaternary amino carbon center to the DA product was achieved with the Tsuji–Trost allylation. The stereochemistry was unambiguously confirmed with X-ray.     

A new method for the synthesis of fused 3-amino-s-triazole ring systems

Reaction of 2-methyl-2-thiopseudourea sulfate with 1-hydrazinophthalazine gave 3-amino-s-triazolo[3,4-a] phthalazine in good yield. 1-Amino-4-methyl-s-triazolo[4,3-a]quinoxaline and 1-amino-s-triazolo[4,3-a]quinoxalin-4(5H)one were similarly perpared.     

A general synthetic route to differentially functionalized angularly and linearly fused [6-7-5] ring systems: a Rh(I)-catalyzed cyclocarbonylation reaction

Investigations of a Rh(I)-catalyzed cyclocarbonylation reaction reveal its general synthetic utility for accessing highly functionalized tricyclic [6-7-5] linear and angular ring systems from allene-ynes. Three types of allene-ynes were prepared and subjected to Rh(I)-catalyzed cyclocarbonylation conditions. For three series of allene-ynes, the [6-7-5] ring systems were afforded in varying yields depending on the substrate structure. One series of allene-ynes afforded the [6-6-5] ring system possessing an alpha-alkylidene cyclopentenone as a result of a selective reaction with the proximal double bond of the allene.     

Toward understanding the scope of Baylis-Hillman reaction: synthesis of 3-(2- hydroxyphenyl)indolin-2-ones and polycyclic fused furans

A facile one-pot synthesis of 3-(2-hydroxyphenyl)indolin-2-ones has been developed via the TiCl₄-mediated Baylis-Hillman (B-H) reaction of N-substituted isatins and cyclohex-2-enone, followed by treatment of the in situ generated B-H alcohols with aq HBr. Baylis-Hillman reaction of aromatic cyclic 1,2-diones with cycloalk-2-enones under the influence of TiCl₄ has been successfully performed and the resulting Baylis-Hillman adducts have been conveniently transformed into pentacyclic and hexacyclic fused furan derivatives.     

Toward the total synthesis of spirastrellolide A. Part 3: intelligence gathering and preparation of a ring-expanded analogue

Different methods for the formation of the C.25-C.26 bond of spirastrellolide A () are evaluated that might qualify for the end game of the projected total synthesis, with emphasis on metathetic ways to forge the macrocyclic frame.     

糖苷键水解过渡态的模拟-2-(对甲氧苯基)-亚氨基哌啶的合成和晶体结构

由戊内酰胺和三氯氧磷, 对甲氧苯胺一步反应合成了2-(对甲氧苯基)-亚胺基哌啶, 并对所得化合物进行IR, UV, ^1H NMR, ^1^3C NMR和X-ray表征。X-ray结果显示含N的六元环是一个半椅式构型, N1, C8, C9, N2, C12基本上在同一平面, N2, C8, N1, C5存在共振结构, 在弱酸体系中其半椅式构型和电荷分布与不稳定的过渡态相类似。     

Efficient and stereoselective synthesis of bicyclo[3.2.1]octan-8-ones: synthesis and palladium-catalyzed isomerization of functionalized 2-vinyl-2,3,3a,4,5,6-hexahydro-2,3-benzofurans

A new C,O-cyclodialkylation of dilithiated cyclic beta-keto esters and beta-keto sulfones with 1,4-dibromo-2-butene is reported which results in regio- and diastereoselective formation of 2-vinyl-2,3,3a,4,5,6-hexahydro-2,3-benzofurans. The products could be efficiently transformed into functionalized bicyclo[3.2.1]octan-8-ones by a palladium-catalyzed rearrangement reaction. In case of sulfone derivatives, this rearrangement proceeds with high stereospecifity to give exclusively the endo-configured diastereomers. The bicyclo[3.2.1]octane skeleton is present in a large number of pharmacologically important natural products.     

Preparative and stereoselective synthesis of the versatile intermediate for carbocyclic nucleosides: effects of the bulky protecting groups to enforce facial selectivity

The preparative and stereoselective synthesis (45-50% overall yields) of the target compound 17 has been accomplished from D-ribose. The bulky protecting groups such as TBDPS and Trityl enforced the facial selectivity during Grignard reaction to give the tertiary beta-allylic alcohol 16 as the sole product, which was oxidatively rearranged to the key molecule 17 in excellent yield.     

2-Dicyanomethylidene-3-ethoxymethylidene-2,3-dihydroindole in the synthesis of fused tri- and tetracyclic systems

The reactions of 2-dicyanomethylidene-3-ethoxymethylidene-2,3-dihydroindole with hydrazine hydrate and phenylhydrazine afforded 2,3-diamino-4-cyanopyrido[4,3-b]indole and 3-amino-2-anilino-4-cyanopyrido[4,3-b]indole, respectively, and the reactions of the latter compounds with dimethylformamide diethyl acetal were studied. The reactions of 2,3-diamino-4-cyanopyrido[4,3-b]indole with benzaldehyde, ethyl acetoacetate, and acetylacetone were investigated. First representatives of new heterocyclic systems, viz., [1,2,4]triazolo[1’,5’:1,6]-pyrido[4,3-b]indole and pyrazolo[1’,5’:1,2]pyrido[4,3-b]indole, were synthesized. The structure of ethyl 6-cyano-5-[(E)-(dimethylamino)methylideneamino]-2-methyl-7H-pyrazolo-[1’,5’:1,2]pyrido[4,3-b]indole-1-carboxylate was established by X-ray diffraction.     

Routes for synthesis of [2′-D3]-2-methyl-2-hepten-6-one

Conclusions Routes were developed for the stereoselective synthesis of the deuterium analog of 2-methyl-2-hepten-6-one, and from it the deuterium analogs of geranium ester.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No.2, pp.384–389, February, 1973.     

A highly stereoselective reductive amination of 3-ketosteroid with amines: an improved synthesis of 3α-aminosteroid

A highly stereoselective reductive amination method was developed based on in situ generated sodium acyloxyborohydride and was successfully applied to a steroidal skeleton with various amine sources. High yield (96%) and a de of up to 95% were achieved by modifying the reducing reagent. The effect of this reagent will be discussed.