Homologation diastereoselective

The enol ether double bond contained within the ds-fused dioxa-bicyclo[3.2.0]heptene photoadducts can also be oxidized, in a completely diastereoselective fashion, with mCPBA. Treatment of intermediate XXII, derived in one step from a Patemo-Buchi reaction between 3,4-dimethylfuran and benzaldehyde, with mCPBA results in the formation of intermediate XXIII. Once again, consecutive photocycloaddition and oxidation reactions furnish a highly oxygenated system that possesses five contiguous stereocenters, one of which is quaternary. Intermediate XXIII is particularly interesting because its constitution and its relative stereochemical relationships bear close homology to a portion of a natural product known as asteltoxin. 

The use of stoichiometric ruthenium-NHC complexes generated in situ from [Ruljd-COCKp-cymene)], an imidazohnm salt [4] or an imidizol(idin)ium-2-carboxylate [4] has been applied in the cyclopropanation of styrene 5 with ethyl diazoacetate (EDA) 6 (Scheme 5.2). No base was necessary when imidazolium-2 carboxylate were employed. The diastereoselectivity was low and the cis/trans ratio was around 50/50 (Table 5.1). Although the diastereoselectivity was moderate, the reaction was highly chemoselectivity as possible side reactions (homologation, dimerisation and metathesis) were totally or partially suppressed. 

The heterocyclic scaffolds are prepared from pyroglutamic acid [154, 155]. 1-aminoalkyl boronic acid pinanediol esters are readily available through a diastereoselective homologation with dichloromethyllithium, providing (5)-a-chloroboronic esters. Aminolysis of the chloride yielded... 

Diastereoselective homologation of chiral alkylboronates (cf. 12, 80-81). Investigations of this reaction have been carried out mainly on boronic esters (1)... 

In contrast to the carbamates, N-tosyl carbamates 18 reacted fast (1-2 h) with LiBr in the presence of copper(II)-oxygen and catalytic amounts of palladium acetate yielding oxazolidinones 19 (Scheme 17.10). The rate enhancement is due to the presence of two electron-withdrawing substituents on nitrogen and is, again, responsible for the diminished diastereoselectivity of the reaction. Attempts to prepare the homologous six-membered heterocycles gave only poor yields. 

In the synthesis of AG5473/5507 (324/325) by Guo et al., many attempts were made to homologate an aldehyde directly through an intermediate acyliminium ion, but without success [68], Finally, a less direct route involving the addition of pro-pargylsilane to 321 afforded the allene 322 with 10 1 diastereoselectivity (Scheme 19.59). Allene 322 was then ozonized to give aldehyde 323 in 90% yield. 

DIASTEREOSELECTIVE HOMOLOGATION OF D-(R)-GLYCERALDEHYDE ACETONIDE USING 2-(TRlMETHYLSILYL)THI AZOLE 2-0-BENZYL-3,4-IS0PR0PYLIDENE-D-ERYTHR0SE (1,3-Dloxolane-4-acetaldehyde, 2,2-dimethyl-a-(phenylmethoxy)-, [R-(R, R )]-)... 

Iterative two-directional chain elongation enables rapid construction of 1,3-polyols (Scheme 23). For example, the polyol substructure that appears in the oxopolyene macrolide (+)-roxaticin is available in nine steps from propane-1,3-diol upon three iterations of double carbonyl allylation [286]. Notably, high levels of catalyst-directed stereoselectivity are observed (For selected examples of catalyst directed diastereoselectivity, see [289-296]). Analogous 1,3-polyol syntheses via iterative homologation in one direction also are reported [297]. 

In contrast to the preceding syntheses of kelsoene. Piers and Orellana used ethylene 8 in the [2-1-2]-photocycloaddition key step to furnish tricyclic ketone rac-lO diastereoselectively (Scheme 2) [11]. In accordance with the report by Srinivas and Mehta, attempts to homologate the sterically encumbered ketone rac-lO using the Wittig, Magnus [18, 19] or Taguchi [20] pro-... 

These include the four possible diastereomeric spirocyclopropane derivatives 633, 685, 634, and 686 resulting from methylene insertion into the double bond and a spirocyclopropane 687 derived from methylene insertion into the double bond of a homologated 5(4f/)-oxazolone. The amount of 687, the cis/trans selectivity and both the cis and trans diastereoselectivities depend on the reaction conditions. Use of nonpolar solvents avoids formation of 687. In addition, the cis/trans selectivity and both cis and trans diastereoselectivities are very high such that the major compound 633 can be isolated in 75% yield (Scheme 7.216). ... 

Carbocupration of chiral alkynylsulfoxides 47 in a regio- and stereospecific manner produces alkenyl organocopper 48, which is subsequently reacted with bis(iodomethyl) zinc in the presence of aldehydes or imines. The zinc carbenoid homologation step leads to 49, the conformation of which is controlled by intramolecular chelation 49 reacts with the aldehyde or imine before it can undergo a -elimination (cf. equation 20). The final product 63 is generally obtained with high diastereoselectivity and in good overall yield (Table 8). 

In this strategy a copper-catalysed carbozincation32 is employed, leading to organozinc 64 which, upon reaction with diiodomethane, undergoes a methylene homologation. Note the excellent diastereoselectivity even for two groups as similar as methyl and methyl-D3 ... 

Borrelidin 1 has attracted attention because it inhibits angiogenesis, and so potentially blocks tumor growth, with an IC of 0.8 nM. Retrosynthetic analysis of 1 led the investigators to the prospective intermediates 2 and 3. To assemble these two fragments, they interatively deployed the elegant enantio- and diastereoselective intermolecular reductive ester aldol condensation that they had recently developed. This transformation is exemplified by the homologation of 4 to 6 catalyzed by the enantiomerically-pure Ir complex 5. 

The cyclization of 1 proceeded with 72 28 diastereoselectivity, leading, after hydrolysis, to the crystalline diketone 8 as the major product Reduction of the ketones to the axial alcohols was followed by spontaneous lactonization, allowing easy differentiation of the several functional groups. Homologation to 10 followed by condensation with methyl carbonate and subsequent O-mcthylation then gave 11. C-Methylation of 11 then set the third quaternary center of the C ring. The deuteriums were introduced to minimize an unwanted intramolecular hydride transfer in a later step. 

Carbonylation with CO in the presence of H2 leads to aldehydes. Bernhard Breit of Albert-Ludwigs-Universitat, Freiburg, has found (Chem. Comm. 2004, 114) that conversion of an allylic alcohol to the o-diphenylphosphanylbenzoate 8 allows highly diastereoselective and regioselective Rh-mediated one-carbon homologation. 

Silylation followed by selenium dioxide oxidation converted 13 into 14. Epoxidation of the derived TES ether proceeded by addition of oxygen to the more open face of the alkene, leading to 15. Ozonolysis followed by diastereoselective one-carbon homologation provided 17. This set the stage for intramolecular epoxide opening by the carboxylate, to give 2, in which all of the stereogenic centers of tetrodotoxin have been established. 

A. Dondoni and P. Merino, Diastereoselective homologation of D-(ft)-glyceraldehyde acetonide using 2-(trimethylsilyl)thiazole 2-0-benzyl-3,4,-0-isopropylidene-D-erythrose, Org. Synth. 72 21 (1993) The procedure has been checked by A. I. Meyers and G. P. Brengel, Colorado State University, USA. 

N. K. Khare, R. K. Sood, and G. O. Aspinall, Diastereoselectivity in the synthesis of D-g/ycero-D-aldoheptoses by 2-(trimethylsilyl)thiazole homologation from hexodialdo-1,5-pyranose derivatives, Can. J. Chem. 72 237 (1994). 

Synthesis of homoallylic amines has been reported by a three-component coupling of aldimines, diiodomethane, and alkenylzirconocenes, in the presence of dimethylzinc (Scheme 28).296,296a The formation of homoallylic products is rationalized by the mechanism shown in Scheme 29. The //////-relationship of the final product is explained by a cyclic chair-like transition state. This type of homologation was used to form f, -dicyclop ropy I ruethylamines by a double C,C-cr-bond insertion into bicyclobutanes (Scheme 30).297 During the course of this cascade process, 10 C,C-bonds are formed, and the final product is isolated in one step with a high diastereoselectivity. 

Chiral homoallylic alcohols and amines were prepared by using a four-component condensation reaction based on a zinc homologation followed by a trapping with an aldehyde or an imine.301 A regio- and stereospecific carbocupration reaction on alkynyl sulfoxide provides the corresponding metallated /3,/3-dialkylated a,/ -ethylenic sufoxide 98. Addition of aldehydes or imines, followed by addition of the bis(iodomethyl)zinc carbenoid, provides adducts 99 in good overall yield and with very high diastereoselectivity (Scheme 36). 

Boronic ester homologation. (R,R)-2,3-Butanediol- and (-(- )-pinanediol have been used as the chiral adjuncts in a diastereoselective homologation of dichloromethaneboronic esters (1) to the (aS)-a-chloroboronic esters (2). Reaction of 1 with an alkyllithium produces a borate complex (a), which rearranges diastereoselectively in the presence of ZnCl, to 2 with introduction of a chiral center adjacent to boron. The reaction permits... 

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