A diastereoselective synthesis

A diastereoselective synthesis of the model insect antifeedant related to 12-hydroxyazadi-radione starting from a-cyclocitral has been reported. [The key steps involve INOC and a Stille... 

Studies of the intramolecular cyclization of P-amino acids have included the use of camphor-derived oxazoline A-oxide 66 and a [3+2] cycloaddition reaction as a step in the formation of the amino acid with the required stereochemistry <00OL1053, OOEJOC1595>. A diastereoselective synthesis of a ip-methylcarbapenem intermediate utilises a cyclization of a P-amino acid <99CC2365>. 

A diastereoselective synthesis of bis(3,5)pyrazolophanes was accomplished by sequential inter- and intramolecular cycloadditions of homochiral nitrilimine intermediates . A-Alkyl pyrazolidine-3,5-diones were synthesized in a three-step sequence from dialkyl malonates <00JHC1209>. Methyl acetoacetate was employed as the initial substrate to 3-carboxamido-4-pyrazolecatboxylic acid derivatives <00JHC175>. Vilsmeier type reagent 33 reacted with imines 34 to afford enaminoimine hydrochlorides 35, which were transformed to pyrazoles 36 upon addition of hydrazine <0OJHC13O9>. 

A diastereoselective synthesis of /3-(iV-acylamino)aldehydes was accomplished via ruthenium-catalyzed isomerization of 0-vinyl-iV,0-acetals followed by rearrangement in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) (Scheme 36).63... 

A diastereoselective synthesis of 3,5-disubstituted indolizidines based on an intermol. addition of an allylsilane on an acyliminium ion derived from (d )-pyroglutamic acid, is described <2006TA1253>. 

Epoxidative lactonization.1 This reaction can be used for a diastereoselective synthesis of 5-hydroxyalkylbutanolides (3) from (E)- and (Z)-4-alkenoic acids (1). Thus epoxidation of (E)-l results in an epoxide (2) that in the presence of acid is converted into erythro-i. In contrast, (Z)-l is converted into threo-3. Yields are essentially quantitative. 

A diastereoselective synthesis of the racemic vinylallene 96 was described by Gordon and Tabacchi [96] in 1992 (Scheme 18.31). Here, the exocyclic allene was formed via anti-SN2 -substitution of the propargylic sulfmate 98 with lithium diisopropenyl-cyanocuprate, which, however, was also found to undergo side reactions such as reduction and direct attack of the nucleophile at the sulfmate. Deprotection of the substitution product 99 (which was obtained with only 35% yield) finally provided the desired target molecule 96. 

A diastereoselective synthesis of vicinal diamines has been described79. The aldehydes 56 derived from chiral amino acids 55 were converted into the A-benzylimines 57 and the latter were treated with organometallic reagents R2M in the presence of cerium(III)... 

Suggest methods that would be expected to achieve a diastereoselective synthesis of the following compounds. 

In regard to the importance of a diastereoselective synthesis of 5-[hydroxy(aryl) methyl]furan-2(5//)-ones, the Bi(OTf)3-4H20-catalyzed vinylogous Mukaiyama aldol has been investigated with 2-(trimethylsilyloxy)furans and various carbonyl compounds [146]. 

In 2005, a diastereoselective synthesis of m-3-alkyl-l-benzyl-4-ethoxycarbonyl-[S-1 act a ms has been reported to be developed by galvanostatic electrolysis of a solution of acetonitrile containing a tetraalkylammonium salt, as supporting electrolyte and /V-(ethoxycarbonyl)methyl-/V-benzyl-2-bromoalkylcarboxamides [165]. The electrogenerated cyanomethyl anion, at room temperature and under a nitrogen atmosphere, caused the cyclization of the substituted carboxamides. High cis/trans ratios were observed with all the substrates exploited, (Scheme 68). 

A diastereoselective synthesis of /3-sultams by 1,3-asymmetric induction in [2+2] cycloaddition of a sulfene intermediate and a chiral imine has been described (Scheme 48), and it was found that jV-alkylirnines give better diastereo-selectivity than iV-arylimines. The best selectivity was found in the case ofiV-(l-/-butylethyl)imine (67% yield, >95% de), and the diastereoselectivity was independent of the size and conformation of the N-substituents in the imines. Diastereoisomers bearing an /V-aryl group were separable by silica gel column chromatography <1998JOC8355>. 

Sultams are accessible using a [2+2] cycloaddition reaction between an alkylsulfonyl chloride and an aryl or /-butylimine, better yields being obtained in the latter case. A diastereoselective synthesis of these /3-sultams has been described where 1,3-asymmetric induction occurs in a [2+2] cycloaddition between a sulfene intermediate and... 

A diastereoselective synthesis of tetrahydropyran-3-ones 1021 can be achieved via [2,3]-sigmatropic rearrangement of the ylides 1022, generated from the achiral diazoketone 1023 via formation of a copper carbenoid followed by an... 

A diastereoselective synthesis of all. fy -2,3,6-trisubstitutcd tetrahydropyran-4-ones 1039 via an intramolecular Prins cyclization of enecarbamates 1038 with aldehydes is used during a formal synthesis of (+)-ratjadone (Equation 403) <2004JA12216>. Similarly, tetrahydropyran-4-ones bearing quaternary centres a-to the carbonyl are accessible via a Lewis acid-mediated Prins cyclization of silyl enol ether substrates <2004JA15662>. 

A single step of the polymerization is analogous to a diastereoselective synthesis. Thus, to achieve a certain level of chemical stereocontrol, chirality of the catalytically active species is necessary. In metallocene catalysis, chirality may be associated with the transition metal, the ligand, or the growing polymer chain (e.g., the terminal monomer unit). Therefore, two basic mechanisms of stereocontrol are possible (145,146) (i) catalytic site control (also referred to as enantiomorphic site control), which is associated with the chirality at the transition metal or the ligand and (ii) chain-end control, which is caused by the chirality of the last inserted monomer unit. These two mechanisms cause the formation of microstructures that may be described by different statistics in catalytic site control, errors are corrected by the (nature (chirality) of the catalytic site (Bernoullian statistics), but chain-end controlled propagation is not capable of correcting the subsequently inserted monomers after a monomer has been incorrectly inserted (Markovian statistics). 

The third type of reactivity, using HTI in trimethyl orthoformate, involved migration of the aryl groups attached to the carbonyl moiety, resulting in a diastereoselective synthesis of methyl 2,3-diaryl-3-methoxypropanoates in their erythro form exclusively. 

An excellent application of the Narasaka reduction is a diastereoselective synthesis by Merck scientists of 7, a structurally novel analog of the natural product compactin (8)7, which is a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase8 (Scheme 4.1e). The key step in the construction of the P-hydroxy-8-lactone moiety in 7 is the highly diastereoselective reduction of the P-hydroxy ketone 9 using a triethyl borane/sodium borohydride system. The yyn-diol 10 was obtained in high yield and with a remarkably high level of diastereoselectivity. 

The substrates are available by diastereoselective alkylation of chiral p-hydroxy acids followed by conversion to the aldehyde and Wittig olefination. The overall process provides a diastereoselective synthesis of compounds with three consecutive asymmetric centers. Tetrahydropyridines.5 Danishefsky has used an intramolecular version of the Giese... 

In a series of papers [23], Tamai et al. reported using l,r-binaphthyl isomers as templates for a diastereoselective synthesis of ester alcohols from the corresponding acyl compounds. They reported a low d.e. of 16% of the ester alcohol [Eq. (8) 23c]. However, their more recent modifications gave improved yields and higher diastereoselectivities. When they added a polyether as a 2 -substituent and lengthened the chain between the dicarbonyls, the 7 -isomer was formed exclusively. Hydrolysis of this product yields the / -lactone. The authors suggest that the cooperative chelation of the oxygen side chain plays an important role in the exclusive formation of the / -enantiomer. 

Roush, W. R., Limherakis, C., Kunz, R. K., Barda, D. A. Diastereoselective Synthesis of the endo- and exo-Spirotetronate Suhunits of the Quartromicins. The First Enantioselective Diels-Alder Reaction of an Acyclic (Z)-1,3-Diene. Org. Lett. 2002,4, 1543-1546. 

The ketene 0,0-acetals 83 were prepared from the corresponding bromo derivatives by reaction with strong base A diastereoselective synthesis of the trans- and cis 84 was carried out. Condensation of substituted aminothiophenols and 2-arylidene-l-tetralone afforded 1,4-thiazepines 85. Condensation of o-phenylenediamines with P-ketoesters or 1,1,1-trifluoromethyl-3-(isobutoxymethylene)-2-propanones gave 84. ... 

A diastereoselective synthesis of azetidines 16 (12 examples with yields in the range (62-82%) by decomposition of azazirconacyclopentanes 15 with iodine is reported <97JOC5953>. The intermediate 15 can be obtained in a zirconium-mediated reaction of A-substituted anilines 14 with an olefin. 

The HDA reaction features in a diastereoselective synthesis of c/j-2,6-disubstituted 5,6-dihydro-2//-pyrans, but this is based on the initial formation of a dihydropyran-4-one. Regio- and stereo- chemistry are controlled during the reduction to the pyranol and an ester enolate Claisen rearrangement completes the sequence <97AJC43>. 

A diastereoselective synthesis of the GH ring part of ciguatoxin (30, X = O, H2) has been reported starting from 2-bromo-2-cyclohexen-l-one. The ring expansion stage is achieved by a Baeyer-Villiger reaction <97SL307>,... 

A diastereoselective synthesis of pyranothiazoles 66 was achieved in a one-pot reaction of the three components glycine, acetic anhydride, and 5-arylidenerhoda-nines 64 by employing MWI under solvent-free conditions. The yields of 66 were 73-86%, compared to 35 3% obtained from conventional heating. The formation of pyranothiazoles 66 occurred through the cyclization of Michael adducts 65... 

Methylenecyclohexenones. A diastereoselective synthesis of a 2-methylene-cyclohexenone (5) involves use of (s)-2-(inethoxymethyl)pyrrolidine (1) as the chiral auxiliary and as the leaving group for generation of the exo-methylene group. 

Reductive N-N cleavage of hydrazines. A diastereoselective synthesis of chiral a-amino aldehydes (4) from glyoxal involves an intermediate dimethylhydrazone (1), which reacts with an alkyllithium to provide an a-substituted N, N -dimethylhydrazine (2). The mildest method for cleavage of hydrazines to primary amines (3) involves hydrogenolysis catalyzed by Raney nickel at 30-50°. This Raney nickel reductive cleavage is markedly improved by sonication and proceeds at atmospheric pressure of H2 at 20° in CH3OH in yields of 66-84% with no racemization or debenyzlation. ... 

The Tan group was the first to report a diastereoselective synthesis of acortatarin A 20 in nine steps and B 21 in ten steps, not counting the steps required to reach the pyrrole intermediate 40. Interestingly, upon completion of the synthesis of acortatarins A 20 and B 21, it was discovered that upon acid-catalyzed equilibration, the favored epimer of acortatarin B 21 was not the natural one. It is postulated that this may indicate that the biosynthesis of acortatarin B 21 is under enzymatic control and not thermodynamic control, as is often the case with spiroketals. 

Intramolecular 1,3-dipolar cycloaddition has been employed for the synthesis of various natural products as well. For instance, Mateos et al. reported a diastereoselective synthesis of the model insect antifeedant 281 related to 12-hydroxyazadiradione utihzing the intramolecular nitrile oxide cycloaddition (Scheme 65) [167]. The nitro compound 279 was synthesized from a-cyclocitral 278 in four steps. The cleavage of isoxazoline 280 was performed under three different conditions Raney Ni-mediated cleavage in methanol-water-acetic acid provided the epimeric ketoalcohol 282 in 5 3 ratio. While there was 100% selectivity in favor of the axial alcohol 282a in the presence of Pd/C and boric acid, the selectivity was in favor of the equatorial alcohol 282b when boric acid was replaced by acetic acid. 

Barber JA, Staunton J, Wilkinson MR (1986) A Diastereoselective Synthesis of the Polyke-tide Antibiotic Citrinin Using Toluate Anion Chemistry. J Chem Soc Perkin Trans 1 2101... 

A diastereoselective synthesis of a-tocopherol 87 features a Shi epoxidation with ent-2 and a carefully controlled intramolecular epoxide opening cyclization for the formation of the chromanol ring. Good conversion and high enantioselectivity have been achieved in the epoxidation step. ... 

In 2000, Roland and Mangeney developed a diastereoselective synthesis of tert-butyl-1,2-diamines from the addition of tert-butylmagnesium chloride to... 

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