Regio- and Stereoselective Syntheses with Organocopper Reagents

Of all of the organometallic reagents currently used to form carbon–carbon bonds, organocopper reagents rank amongst the most important. Interest in these reagents centers not only on their regioselectivity, but also increasingly on their application in stereoselective transformations (principally Michael additions and S_N2′ reactions); the use of suitable substrates or chirally modified cuprates can lead to highly diastereo- and enantioselective reactions. Simultaneously, extensions of methods for the preparation and application of these reagents (for example functionalized organocopper species and Lewis acid catalysis, respectively) have opened up new horizons for organocopper reagents. Mechanistically, the reactions are well-documented and understood, but this aspect of the subject has not kept pace with the many rapid developments in preparative chemistry. Organocopper ragents have proved to be indispensable in the synthesis of complex natural products and pharmaceuticals, chiral auxiliaries, and molecules with interesting structural features. In this review we will discuss some of the more recent important developments in this area; the organization will follow the type of selectivity (regio-, diastereo-, and enantioselectivity).     

Carbohydrate Auxiliaries in Stereoselective Syntheses of Decahydroquinoline Alkaloids

Summary.  Using tetra-O-pivaloyl-β-D-galactopyranosylamine as the chiral auxiliary, both trans- and cis-annelated decahydroquinoline alkaloids can be synthesized stereoselectively. This methodology of asymmetric synthesis is based on the effect that both enantiomers of 2,6-disubstituted piperidin-4-ones are selectively and alternatively accessible using the auxiliary as the identical stereodifferentiating tool. In addition, the carbohydrate auxiliary controls the stereoselective protonation of enolates formed by conjugate addition of cuprates to N-galactosyl octahydroquinolin-4-ones. The syntheses of trans-4a-epi-pumiliotoxin C and cis-4a-epi-perhydro-219A illustrate this concept of asymmetric synthesis of decahydroquinoline alkaloids. Received September 7, 2001. Accepted October 16, 2001     

A Short and Highly Stereoselective Synthesis of Cerebrosterol

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Regiocontrolled and Stereoselective Syntheses of Tetrahydrophthalazine Derivatives using Radical Cyclizations

Tetrahydrophthalazine derivatives have found important applications in pharmaceutical research, but existing synthetic methods are unable to access them regio- and stereoselectively. Here, a new approach is presented that addresses these challenges by utilizing a 6-endo-trig radical cyclization in the key step. The desired tetrahydrophthalazines can be accessed in high yields (55–98 %) and high diastereoselectivities for the trans-product (>95:5) starting either from readily accessible hydrazones, or from the corresponding aldehydes and substituted Boc-hydrazides in a one-pot process. The synthetic versatility of the tetrahydrophthalazine core was demonstrated by its straightforward conversion to dihydro-phthalazines, phthalazines, or pyrazolo dione derivatives. Furthermore, the N−N bond was reduced to afford a new route to 1,4-diamines.     

A Short Syntheses of 1,2-Dimethylazulenes

Dimethyl azulene-1,2-dicarboxylates are reduced with a 4–5 molar excess of DIBAH in Et₂O/hexane at 0° to yield the corresponding 2-(hydroxymethyl)-1-methylazulenes which can be further reduced to 1,2-dimethylazulenes on treatment with Et₃SiH in TFA at 60° (cf. the Table).     

Facile Synthesis of Mill Moth's Sex Pheromone Components

An improved method for the preparation of mill moth's sex pheromone components in high diastereomeric purity is described.     

Stereoselective Syntheses of the Isomeric 5, 10-Pentadecadienals

The four isomeric 5, 10-pentadecadienals 1 , 2 , 3 and 4 were prepared by stereo-selective routes from acetylenic precursors. Two of them, 2 and 4 , were also made by Wittig reaction from 2-hydroxytetrahydropyran (29) . 2-Hydroxytetrahydropyran (29) yields (Z)-5-alkenols efficiently by Wittig reaction, and (Z)-4-hexenol was similarly made from 2-hydroxytetrahydrofuran (66) .     

Short Syntheses of Unsaturated Aliphatic Ketone Pheromones

While most pheromones of Lepidoptera are unsaturated aldehydes, alcohols or acetates with the oxidated carbon usually being the first carbon of the aliphatic chain, there are some pheromone examples where an intermediate carbon other than the first one is present in an oxidized state. Such is the case of the pheromone of the peach fruit moth, Carposina niponensis, a mixture of (Z)-7-eicosen-11-one and (Z)-7-nonadecen-11-one¹ and of the Douglas fir tussock moth, Orgya pseudotsugata, for which a single component, (Z)-6-heneicosen-11-one, has been isolated².     

Stereoselective Syntheses of all the Possible Stereoisomers of Coronafacic Acid

An efficient and stereoselective syntheses of all the possible stereoisomers of coronafacic acid (CFA) has been developed. The stereochemistries of C3a and C7a were controlled in a diastereoselective Diels-Alder type cycloaddition using a chiral auxiliary. CFA and 6-epi-CFA were synthesized by hydrogenation of a common intermediate. During the synthesis of 6-epi-CFA, we established that its cis-fused configuration is important for the introduction of C4-C5 double bond by dehydration. This report is the first practical synthesis of both 6-epi-CFA, and its enantiomer.     

Stereoselective Syntheses of Tetrahydroesterastin-β -Lactam Analogues

A total synthesis of the optically active tetrahydroesterastin β -lactam analogue 2 using Miller's hydroxamate approach is described (Scheme 2). Significant modification of published procedures has resulted in a short and facile stereospecific preparation of the N-[(benzyloxycarbonyl)methyl]-β -lactam 17 starting from the readily available D -serine. This material served as intermediate for the preparation of a variety of N-[(benzyloxycarbonyl)methyl]tetrahydroesterastin β-lactam analogues (Scheme 5).     

淡色库蚊产卵引诱信息素的立体选择性合成

手性烯醇硅醚——薄荷烷氧基二甲硅烷基环戊用烯醇硅醚与十一醛进行立体选择性亲电取代反应，得到赤式占优势的２－（１－羟基十一烷基）环戊酮，分离纯化后经Ｂａｃｙｅｒ－Ｖｉｌｌｉｇｅｒ重排和乙酰化，得到淡色库蚊产卵引诱信息素——赤式６－乙酰氧基十六碳烷酸－５－内酯。其中活性组分（－）－（５Ｒ，６Ｓ）异构体占５０％，较一般非立体选择性合成法提高２５％。     

Short Efficient Syntheses of 2,2-Dimethyl-2H-Pyranopyridines

Syntheses of [3,2-c]-,[3,2-b]-,and [2,3-c]-2,2-dimethyl-2H-pyranopyridines via Claisen rearrangement of propargyl ethers are described. An alternative approach to the [2,3-b]-isomer is reported.     

从鹅去氧胆酸甲酯用简短和高立体选择性方法合成角鲨多胺

A short and highly stereoselective synthesis of squalamine (1) was accomplished in 9 steps from easily available methyl chenodeoxycholanate (2). The advanced intermediate 7α,24R-dihydroxy-cholestan-3-one (9) was synthesized by using improved dehydrogenation of 4 followed by conjugate reduction and efficient asymmetric isopropylation of aldehyde 7 as key reactions.     

Practical Synthesis of Pheromone Components of Achaea Janata (Noctuidae)

A practical synthesis of pheromone components of Achaea janata utilising double alkylations on TosMIC as key steps has been achieved.     

Enantioselective Syntheses and Absolute Configurations of Viridiene and Aucantene,Two Constitutents of Algae Pheromone Bouquets

Viridiene ((+)- 6 ; (+)-(3R,4S)-3-((1Z)-1,3-butadienyl)-4-vinylcyclopentene) and aucantene ((+)- 18 ; (+)-(4R,5R)-4-((1E)-1-propenyl)-5-vinylcyclohexene) are constituents of the pheromone bouquets of several brown algae species. Key synthons to the title compounds are optically active γ-lactones with known or experimentally determined absolute configurations. Horse liver alcohol dehydrogenase, which catalyses the oxidation of meso- and racemic non-meso diols to chiral lactones, and pig-liver esterase, which catalyzes the saponification of meso-diesters to chiral half-esters, were utilized for the asymmetric synthesis of such precursors. The racemic non-meso diol rac- 1 is converted to the two stereoisomeric γ-lactones (+)- 2 and (+)- 3 which are readily separated. meso-Diol 12 is oxidized to the chiral γ-lactone (?)- 11 . Its enantiomer (+)- 11 is obtained by enantioselective saponification of the meso-diester 9 with pig-liver esterase. Appropriately designed syntheses lead from these chiral intermediates to both enantiomers (+)- and (?)- 6 of viridiene and (+)- and (?)- 18 of aucantene. In addition, kinetically controlled reduction of the racemic aldehydes rac- 5a and rac- 15 with horse liver alcohol dehydrogenase offers a convenient alternative to the enantioselective preparation of the enantiomers of the two hydrocarbons 6 and 18 . Chromatography of 6 on triacetylated cellulose as a stationary chiral phase confirms the enantiospecificity of the synthetic routes designed.     

The Facial and Short Method for the Synthesis of Z/E-Isomers of Acetate of 12-Tetradecene-1-ol Components of the Sex Pheromone Ostrinia furnacalis

Chemistry of Natural Compounds - The sex pheromones of Ostrinia furnacalis Z/E-isomers of acetate of 12-tetradecene-1-ol were synthesized in an overall yield of 44.5% with 1,12-dodecanediol as a...     

Quantitative Prediction of Rate Constants for Aqueous Racemization To Avoid Pointless Stereoselective Syntheses

Racemization has a large impact upon the biological properties of molecules but the chemical scope of compounds with known rate constants for racemization in aqueous conditions was hitherto limited. To address this remarkable blind spot, we have measured the kinetics for racemization of 28 compounds using circular dichroism and ¹H NMR spectroscopy. We show that rate constants for racemization (measured by ourselves and others) correlate well with deprotonation energies from quantum mechanical (QM) and group contribution calculations. Such calculations thus provide predictions of the second‐order rate constants for general‐base‐catalyzed racemization that are usefully accurate. When applied to recent publications describing the stereoselective synthesis of compounds of purported biological value, the calculations reveal that racemization would be sufficiently fast to render these expensive syntheses pointless.