Alkenes diastereoisomers

In a formal synthesis of fasicularin, the critical spirocyclic ketone intermediate 183 was obtained by use of the rearrangement reaction of the silyloxy epoxide 182, derived from the unsaturated alcohol 180. Alkene 180 was epoxidized with DMDO to produce epoxy alcohol 181 as a single diastereoisomer, which was transformed into the trimethyl silyl ether derivative 182. Treatment of 182 with HCU resulted in smooth ring-expansion to produce spiro compound 183, which was subsequently elaborated to the desired natural product (Scheme 8.46) [88]. 

Ketosilanes react with alkyl lithiums in a diastereoselective manner (7), the preferred diastereoisomer being the one predicted on the basis of Cram s Rule acidic or basic treatment provides a stereoselective route to trisubstituted alkenes. 

Where, as with (24) above, both Cp and C are chiral, elimination from the two conformations will lead to different products—the trans-alkene (25) from (24a) and the cis-alkene (26) from (24b). Thus knowing the configuration of the original diastereoisomer (e.g. 24), and establishing the configuration of the geometrical isomeride(s) that is formed, enables us to establish the degree of stereoselectivity of the elimination process. In most simple acyclic cases, ANTI elimination is found to be very much preferred, e.g. in about the simplest system, (26) and (27), that permits of stereochemical distinction ... 

Concerted cycloaddition reactions provide the most powerful way to stereospecific creations of new chiral centers in organic molecules. In a manner similar to the Diels-Alder reaction, a pair of diastereoisomers, the endo and exo isomers, can be formed (Eq. 8.45). The endo selectivity in the Diels-Alder arises from secondary 7I-orbital interactions, but this interaction is small in 1,3-dipolar cycloaddition. If alkenes, or 1,3-dipoles, contain a chiral center(s), the approach toward one of the faces of the alkene or the 1,3-dipole can be discriminated. Such selectivity is defined as diastereomeric excess (de). 

The use of reductive alkylation conditions has been employed to access tricycles from the azide 353 <2002S242> (Equation 95). Hydroboration of the alkene double bond with dicyclohexylborane followed by reaction with the azide and subsequent elimination of nitrogen and cyclization gave the linear tricyclic diketopiperazine 354 and 355 as a mixture of diastereoisomers. 

Scheme 6.186) [347]. The condensation of O-allylic and O-propargylic salicylalde-hydes with a-amino esters was carried out either in the absence of a solvent or - if both components were solids - in a minimal volume of xylene. All reactions performed under microwave conditions rapidly proceeded to completion within a few minutes and typically provided higher yields compared to the corresponding thermal protocols. In the case of intramolecular alkene cycloadditions, mixtures of hexa-hydrochromeno[4,3-b]pyrrole diastereoisomers were obtained, whereas transformations involving alkyne tethers provided chromeno[4,3-b]pyrroles directly after in situ oxidation with elemental sulfur (Scheme 6.186). Independent work by Pospisil and Potacek involved very similar transformations under strictly solvent-free conditions [348]. 

Cycloaddition of 3-methylenephthalide with ot./V-diphenylnitrone gave two diastereoisomers of 2,3-diphenyl-2,3-dihydrospiro 1,3-oxazole-5(47/ )l (3 H)-2-benzoluran]-3 -one (805). The 1,3-dipolar cycloaddition reaction of /V-benzyl-C-(2-furyl)nitrones with electron-rich alkenes gave preferentially trans-3,5-disubstituted isoxazolidines (endo approach). These experimental results are in good qualitative agreement with those predicted from semiempirical (AMI and PM3) and ab initio (HF/3-21G) calculations (806). 

The presence of this bulky group leads to a higher diastereoselectivity than in the unsubstituted case because interactions of the alkene with the titanocene group lead to the exclusive formation of one diastereoisomer, presumably through the most favored transition structure shown in Scheme 12.19, in which steric interactions should be minimized. 

Phosphorylated derivatives of /3-nitroalcohols, upon exposure to Bu3SnH and AIBN, afford /3-(phosphatoxy)alkyl radicals. These radicals undergo heterolytic cleavage of the phosphate group to afford an alkene radical cation which is trapped intramolecularly in a tandem polar/radical crossover sequence. Derivative 37 (Scheme 13), through a 6-exol 5-exo overall cyclization, afforded the indolizidine derivative 38 as an equimolecular mixture of two diastereoisomers <2003JA7942, 2002OL2573>. 

Diastereoisomers are stereoisomers which do NOT have a mirror image of one another. Figure 11.20 shows the diastereoisomers of 2-butene (alkenes such as this are sometimes called geometric isomers and are a consequence of the prohibition of rotation about double bonds). If a vertical mirror was placed between the two structures in Fig. 11.20 they would not reflect onto one another. If the functionality is on the same side then the isomer is the cis-form, if on the opposite side then it is the trans- form. The chemical properties are very similar because the functional groups are identical. However, as they have different shapes their physical properties are different. Interconversion requires breaking and remaking bonds so these isomers are also stable under normal conditions. 

In an attempt to establish the limits for ODPM reactivity of (B.y-unsaturated aldehydes, we have extended our studies to a series of aldehydes 65, (Scheme 10) which are monosubstituted at C-2. Triplet-sensitized irradiation of 65 leads to the formation of the corresponding cyclopropanecarbaldehydes 66 [59] (Scheme 10). The diphenyl-substituted aldehydes 65b and 65d yield, in addition to the ODPM products, the corresponding alkenes 67a and 67b, resulting from photodecarbonylation. The formation of these alkenes is probably due to stabilization of the radical, formed by allylic cleavage, by diphenyl conjugation. The ODPM rearrangement of aldehydes 65 is diastereoselective, yielding only one diastereoisomer of 66 (Scheme 10). 

More recently, in light of the development of the Sharpless asymmetric dihydroxylation protocol [20], we have approached the synthesis of diols such as 14 (Scheme 2) from the alkene. Thus, treatment of the alkenyl D-glucosides 15 vmder the conditions of the Sharpless dihydroxylation gave a range of diols 16 with varying diastereoisomeric excesses (Table 1). One of these mixtures of diols, upon recrystallization, yielded the pure diastereoisomer, namely the diol 14. This procedure now gives a very rapid and efficient entry into one of the precursor diols for the synthesis of the optically-pure epoxides [21]. 

R = Me) under standard generation conditions, in the presence of activated alkene dipolarophiles led to the expected adducts (Scheme 3.49). In the case of trans-l-nitro-2-(3,4-methylenedioxyphenyl) ethene, a 3 2 mixture of diastereoisomers was isolated. Replacement of the methyl group with a methyl ether (R = CH20Me),... 

Optically active aldehydes are available in abundance from amino and hydroxy acids or from carbohydrates, thereby providing a great variety of optically active nitrile oxides via the corresponding oximes. Unfortunately, sufficient 1,4- or 1,3-asymmetric induction in cycloaddition to 1-alkenes or 1,2-disubstituted alkenes has still not been achieved. This represents an interesting problem that will surely be tackled in the years to come. On the other hand, cycloadditions with achiral olefins lead to 1 1 mixtures of diastereoisomers, that on separation furnish pure enantiomers with two or more stereocenters. This process is, of course, related to the separation of racemic mixtures, also leading to both enantiomers with 50% maximum yield for each. There has been a number of applications of this principle in synthesis. Chiral nitrile oxides are stereochemicaUy neutral, and consequently 1,2-induction from achiral alkenes can fully be exploited (see Table 6.10). 

The analogous reaction of the bicyclic alkene, 5,6,7,8-tetrahydrochroman 261, gave an epimeric mixture of the tricyclic pyrano-l,2,4-trioxane diastereoisomers 262a and 262b in a ratio of 1.5 1 (Scheme 44) <1997H(46)451>. 

The reaction of phenyl-substituted alkenes (2-phenylprop-l-ene, ( )-l-phenylprop-l-ene, 1,1-diphenylethene, 1,1-diphenylprop-l-ene) with F-Teda BF4 (6) in the presence of various alcohols results in the formation of vicinal fluoro alkoxy adducts with Markovnikov-type regioselec-tivity.89,94 The stereochemistry of the fluorination-methoxylation addition reaction is slightly syn predominant in the case of (Z)-stilbene, indene, and dibenzosuberenone, while equal amounts of both diastereoisomers are formed in the case of ( )-l-phenylprop-l-ene and acenaphthylene. 

Optically active ds.vic-diofa.1 It is known that pyridine catalyzes the hydroxyl-ation of alkenes with Os04 and that the osmate ester intermediates form an isolable complex with pyridine (1, 760-761). Hentges and Sharpless reasoned that a similar chiral amine could induce chirality in the diol. And indeed addition of 1 equivalent of 1 or of the C8-diastereoisomer, dihydroquinidine acetate (2), does result in vic-diols in fair to high enantiomeric excess, particularly in reactions performed in toluene at —78°. Opposite stereoselectivities are exhibited by 1 and 2. Optical yields range from 25 to 85%. Use of an amine in which the chiral center is two carbon atoms removed from the coordination site lowers the optical yield to 3 18%. 

An enantioselective synthesis of (+)-estradiol has been accomplished from 1,3-dihy-drobenzo[c]thiophene 2,2-dioxide (306) by successive thermal S02-extrusion and cycloaddition (80HCA1703). Treatment of the optically active iodide (307) with two mole equivalents of the masked quinodimethane (306) in the presence of two mole equivalents of sodium hydride gave (308) as a 1 1 mixture of diastereoisomers. Thermolysis of this alkenic sulfone in 1,2,4-trichlorobenzene furnished the trans-anti-trans steroid (309) in 80% yield. Treatment of (309) with methyllithium gave the methyl ketone, which was subjected to a Baeyer-Villiger oxidation and then silyl ether-acetate cleavage to afford (-l-)-estradiol (310 Scheme 66). 

Alkenes which have no symmetry planes perpendicular to the plane of the double bond such as Pmr-butene-2 or propene can coordinate to platinum in two enantiomorphous ways (77) and (78). If an optically active ligand is also bound to platinum(H), then two diastereoisomers are found which can be separated by fractional crystallization657,658 or by HPLC.659 Both cis and trans isomers of complexes PtCl(N—0)(alkene) have beenprepared, where N—O is an anion derived from an amino add (equations 235a and 235b).660-664 Epimerization cannot occur by simple rotation of the alkene about its bond axis, but only by a mechanism involving cleavage of the platinum(II)-alkene bond. 

Halpem and co-workers have carried out a detailed investigation of the mechanism of the asymmetric hydrogenation of methyl (MAC) and ethyl (EAC) (Z)-a-acetamidodnnamate by rhodium complexes of the ligands DIPAMP (50) and CHIRAPHOS (51).259 Coordination of alkene precedes the oxidative addition of hydrogen. For both ligands, one of the two possible diastereoisomers of the rhodium-diphosphine-alkene complex predominates in solution to a large extent. From the reaction of EAC with the S,S-CHIRAPHOS complex, this diastereoisomer has been isolated. Its structure is represented in (57).260... 

Halpern has shown that this predominant isomer exhibits negligible activity towards the oxidative addition of hydrogen. The minor isomer, which could be detected in solution for DIPAMP but not for CHIRAPHOS, reacts far more rapidly with hydrogen and is responsible for producing the major enantiomer of the hydrogenation product. The optical selectivity is thus due to this difference in reaction rates and not simply to the preferred manner of coordination of the alkene to the rhodium-diphosphine species.259,260 The precise reasons for this large difference in the rates of reaction of the two diastereoisomers with hydrogen are not yet known. The full mechanism is shown in Scheme 14. 

The mechanism requires that the initial alkene coordination step be reversible, otherwise all of the rhodium would soon be present as the major diastereoisomer of the alkene complex and the reaction could then only proceed by this route, reversing the optical selectivity and drastically... 

The N-sulfonyloxaziridines are an important class of selective, aprotic oxidizing reagents.12 Enantiomerically pure N-sulfonyloxaziridines have been used in the asymmetric oxidation of sulfides to sulfoxides (30-91% ee),13 selenides to selenoxides (8-9% ee),14 disulfides to thiosulfinates (2-13% ee),5 and in the asymmetric epoxidation of alkenes (19-65% ee).15-16 Oxidation of optically active sulfonimines (R S02N=CHAr) affords mixtures of N-sulfonyloxaziridine diastereoisomers requiring separation by crystallization and/or chromatography.13... 

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