Stereoselective synthesis of

Total syntheses have been reported by E.J. Corey (1978B, 1979). We outline only the stereoselective synthesis of a protected fragment (A) which contains carbon atoms 1—9. This fragment was combined with fragment (B) by a Grignard reaction and cyclized by one of the methods typical for macrolide formation (see p. 146). 

The coupling of alkenylboranes with alkenyl halides is particularly useful for the stereoselective synthesis of conjugated dienes of the four possible double bond isomers[499]. The E and Z forms of vinylboron compounds can be prepared by hydroboration of alkynes and haloalkynes, and their reaction with ( ) or (Z)-vinyl iodides or bromides proceeds without isomerization, and the conjugated dienes of four possible isomeric forms can be prepared in high purity. 

Conjugated dienes, upon complexation with metal carbonyl complexes, are activated for Friedel-Crafts acylation reaction at the akyhc position. Such reactions are increasingly being used in the stereoselective synthesis of acylated dienes. Friedel-Crafts acetylation of... 

Despite the progress made in the stereoselective synthesis of (R)-pantothenic acid since the mid-1980s, the commercial chemical synthesis still involves resolution of racemic pantolactone. Recent (ca 1997) synthetic efforts have been directed toward developing a method for enantioselective synthesis of (R)-pantolactone by either chemical or microbial reduction of ketopantolactone. Microbial reduction of ketopantolactone is a promising area for future research. 

The stereoselective synthesis of y-bisabolenes was made possible by the development of a new method for the carbosilylation and double alkylation of an acetylenic function coupled with ring closure, overall addition of three carbon substituents to two acetylenic carbons. 

Darzens reaction can be used to efficiently complete the stereoselective synthesis of a"-substituted epoxy ketones. As an example, Enders and Hett reported a technique for the asymmetric synthesis of a"-silylated a,P-epoxy ketones. Thus, optically active a -silyl a-bromoketone 38 was treated with LDA followed by the addition of benzaldehyde to give a"-silyl epoxyketone 40 in 66% yield with good... 

Strategies for stereoselective synthesis of molecules with remote stereoge-nic centers across a double bond of fixed configuration in particular, for synthesis of heterocycles, especially unsaturated macrocyclic lactones 99JCS(P1)1899. 

Contribution of Prof. D. A. Evans to stereoselective synthesis of heterocycles with C—C bond formation (self-review) 99T8589. 

A-Sulfonylimines as useful synthons in stereoselective synthesis of heterocycles 97MI40. 

Stereoselective synthesis of epoxides andaziridines viaylide routes 99PAC369. 

The concept of transient chirality in stereoselective synthesis of five-membered heterocycles using the retro-Diels-Alder methodology 99CRV1163. Five-member heteryladamantanes 99ZOR183. 

Regio- and stereoselective synthesis of y-alkylidenebutenolides and related compounds 97T6707. 

Chiral 4,5-disubstituted oxazolidin-2-ones in stereoselective synthesis of (3-hydroxy-a-amino acids 97G475. 

Recently this [2,3]-Wittig rearrangement has received much attention and has been developed into a useful method for the stereoselective synthesis of homoal-lylic alcohols. 

Jackson and coworkers have used a new approach to the synthesis of fi-hydtoxy-ct-amino acids using farylthio nitrooxiranes. c-Jsopropylideneglyceraldehyde is converted into the corresponding 1-arylthio-l-nitroalkene, which is a key material for stereoselective synthesis of fi,Y-dihydroxyamino acids fScheme 4.6. The key step is stereoselective nucleophilic epoxlda-donof the Tarylthio-Tnltroalkene. Sy)i and ruin epoxides are selecdvely obtained by appropriate choice of epoxidadon reagent." ... 

An expedient and stereoselective synthesis of bicyclic ketone 30 exemplifies the utility and elegance of Corey s new catalytic system (see Scheme 8). Reaction of the (R)-tryptophan-derived oxazaboro-lidine 42 (5 mol %), 5-(benzyloxymethyl)-l,3-cyclopentadiene 26, and 2-bromoacrolein (43) at -78 °C in methylene chloride gives, after eight hours, diastereomeric adducts 44 in a yield of 83 % (95 5 exo.endo diastereoselectivity 96 4 enantioselectivity for the exo isomer). After reaction, the /V-tosyltryptophan can be recovered for reuse. The basic premise is that oxazaborolidine 42 induces the Diels-Alder reaction between intermediates 26 and 43 to proceed through a transition state geometry that maximizes attractive donor-acceptor interactions. Coordination of the dienophile at the face of boron that is cis to the 3-indolylmethyl substituent is thus favored.19d f Treatment of the 95 5 mixture of exo/endo diastereo-mers with 5 mol % aqueous AgNC>3 selectively converts the minor, but more reactive, endo aldehyde diastereomer into water-soluble... 

One of the most efficient methods for the stereoselective synthesis of vinylazir-... 

As described in Section 2.3.2, vinylaziridines are versatile intermediates for the stereoselective synthesis of (E)-alkene dipeptide isosteres. One of the simplest methods for the synthesis of alkene isosteres such as 242 and 243 via aziridine derivatives of type 240 and 241 (Scheme 2.59) involves the use of chiral anti- and syn-amino alcohols 238 and 239, synthesizable in turn from various chiral amino aldehydes 237. However, when a chiral N-protected amino aldehyde derived from a natural ot-amino acid is treated with an organometallic reagent such as vinylmag-nesium bromide, a mixture of anti- and syn-amino alcohols 238 and 239 is always obtained. Highly stereoselective syntheses of either anti- or syn-amino alcohols 238 or 239, and hence 2,3-trans- or 2,3-as-3-alkyl-2-vinylaziridines 240 or 241, from readily available amino aldehydes 237 had thus hitherto been difficult. Ibuka and coworkers overcame this difficulty by developing an extremely useful epimerization of vinylaziridines. Palladium(0)-catalyzed reactions of 2,3-trons-2-vinylaziri-dines 240 afforded the thermodynamically more stable 2,3-cis isomers 241 predominantly over 240 (241 240 >94 6) through 7i-allylpalladium intermediates, in accordance with ab initio calculations [29]. This epimerization allowed a highly stereoselective synthesis of (E) -alkene dipeptide isosteres 243 with the desired L,L-... 

The alkynyl reagent 9 was recently introduced for the dia stereoselective synthesis of tertiary propargylic alcohols144. 9 can be prepared as a solid 1 1 complex with tetrahydrofuran by treatment of 9-methoxy-9-borabicyclo[3.3.1]nonane with (trimethylsilylethynyl)lithium, followed by addition of boron trifluoride-diethyl ether complex. The nucleophilic addition of reagent 9 to (R)-2-methoxy-2-methylhexanal (10) afforded a mixture of the diastereomers 11 with a considerable preference to the nonchelation-controlled (3S,4R)-isomer144. 

Allylboron compounds have proven to be an exceedingly useful class of allylmetal reagents for the stereoselective synthesis of homoallylic alcohols via reactions with carbonyl compounds, especially aldehydes1. The reactions of allylboron compounds and aldehydes proceed by way of cyclic transition states with predictable transmission of olefinic stereochemistry to anti (from L-alkene precursors) or syn (from Z-alkene precursors) relationships about the newly formed carbon-carbon bond. This stereochemical feature, classified as simple diastereoselection, is general for Type I allylorganometallicslb. 

The Ireland-Claisen reaction of ( )-vinylsilanes has been applied to the stereoselective synthesis of syn- and c/nti-2-substituted 3-silyl alkcnoic acids. a R-2-Alkyl-3-silyl acids are prepared by rearrangement of ( )-silyl ketene acetals which are generated in situ from the kinetically formed (Z)-enolate of the corresponding propionate ester40. Chelation directs the stereochemistry of enolization of heteroelement-substituted acetates in such a way that the syn-diastereomers are invariably formed on rearrangement403. 

An interesting and stereoselective synthesis of 1,3-diols has been developed which is based on Lewis acid promoted reactions of /f-(2-propenylsilyloxy (aldehydes. Using titanium(IV) chloride intramolecular allyl transfer takes place to give predominantly Ag/r-l,3-diols, whereas anti-1,3-diols, formed via an / / /-molecular process, are obtained using tin(IV) chloride or boron trifluoride diethyl ether complex71. 

Allylic titanates having an electrofugal leaving group, e.g., trimethylsilyl68 75 - 77, at the 3-position are powerful reagents for the highly stereoselective synthesis of 1-hetero-substituted 3-alkadienes. For the carbonyl addition of the appropriate titanated allyl sulfides ( ) or carbamates ( and ), reliable y-selectivity and anti diastereoselectivity are reported. The... 

A matched pair combination of the above silylketene acetal and (/ ,if)-2,4-dimethyl-2-heptenal has been applied in a stereoselective synthesis of the C17-C25 fragment of zincophor-... 

The enzyme-catalyzed stereoselective synthesis of (/ )- and (S )-cyanohydrins allows a simple access to compounds which can be easily transformed into the corresponding a-hydroxy-car-boxylic acids (see Table 2)20,21,23, a-hydroxyaldehydes26 or acyloins27, without racemization. 

Despite the lability of the N — O bond, addition of organomctallic reagents to 5-substituted isoxa-zolines provides a potential route for stereoselective synthesis of substituted 3-amino alcohols1. 

Table 1. Stereoselective Synthesis of a-Hydrogcnamino Acids Using 5-Amino-2,2-dimethyl-4-phenyl-1,3-dioxane as the Auxiliary51 53...

Stereoselective Strecker reactions with galactosylamine 1 can also be achieved with sodium cyanide and acetic acid in 2-propanol. The reactions, however, proceed slowly and with a lower stereoselectivity, giving diastereomeric ratios of the products between 3 1 and 7 1. The scope of the method can be extended to other glycosylamines, e.g., 2,3,4-tri-O-pivaloyl-a-D-arabinosyl-amine which allows the stereoselective synthesis of (A )-amino nitriles61,62. 

This strategy resulted in a direct and stereoselective synthesis of the dolestane skeleton, in which the relative configuration at the quaternary C-5 and C-12 carbons was established. It was shown that the key reaction produced the tricyclic compound slereospecifically in a remarkably high chemical yield57. 

A convenient method for the stereoselective synthesis of sv -3-substituled glutamic acids is based upon the Michael addition oflithium enolates of jV.A -dibenzylglycinates to a,/J-unsatu-... 

A great achievement of the stereochemistry of organosulphur compounds was the stereoselective synthesis of optically active sulphoxides developed by Andersen in 1962342. This approach to sulphoxides of high optical purity, still most important and widely used,... 

Based on the facile formation and reactivity of323, and the retro Diels-Alder reaction of 325306,310, a simple procedure has been developed for the stereoselective synthesis of functionalized conjugated dienes as well as vinylallenes311 (see equation 119). 

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