Diastereoselective synthesis double

The reactions of allylboronates 1 (R = H or CH3) may proceed either by way of transition state 3, in which the a-substituent X adopts an axial position, or 4 in which X occupies an equatorial position. These two pathways are easily distinguished since 3 provides 7 with a Z-olefin, whereas 4 provides 8 with an E-olefinic linkage. There is also a second fundamental stereochemical difference between these two transition states 7 and 8 are heterochirally related from reactions in which 1 is not racemic. That is, 7 and 8 arc enantiomers once the stereochemistry-associated with the double bond is destroyed. Thus, the selectivity for reaction by way of 3 in preference to 4, or via 6 in preference to 5 in reactions of a-subsliluted (Z)-2-butenylboronate 2, is an important factor that determines the suitability of these reagents for applications in enantioselective or acyclic diastereoselective synthesis. 

Finally, by a diastereoselective intramolecular double Michael reaction of a lithium dieno-late to an a,j6-unsaturated ester moiety, a spiro-fused bicyclo[2.2.2]octane may be prepared. These MIMIRC form the key step in the synthesis of ( )-atisine361 and (-t-)-alisirene362-365. 

An important example of heterogeneous diastereoselective synthesis by catalytic way is the synthesis of prostaglandines (a family of compounds having the 20-carbon skeleton of the prostanoic acid) (Scheme 14.14). Naturally, these molecules are biosynthesized via a cyclooxygenase enzyme system that is widely distributed in mammalian tissues. Many of the synthetic routes [272] involve the diastereoselective hydrogenation of a carbonylic bond having a C=C double bond... 

Urea 32, the bis-(mono-trifluoromethyl)phenyl derivative of urea catalyst 16 [178], was reported to operate as double hydrogen-bonding organocatalyst in the diastereoselective synthesis of y-butenolide products substituted at the y-position... 

A striking example of the power of A -heterocyclic carbene (NHC)-bearing catalysts with sterically demanding substrates was disclosed by Chavez and Jacobsen, " who presented a route to several iridoid natural products, exemplified by the enantio- and diastereoselective synthesis of boschnialactone 31 outlined in Scheme 5. Chiral aldehyde 27, available from citronellal by Eschenmoser-methylenation in a single step, reacted despite the presence of an isoprenyl moiety and a gi OT-disubstituted double bond, in the presence of catalyst C smoothly to form... 

Simple double aza-Michael reaction of divinyl ketones with primary amines was utilized to generate TV-substituted 3-phenyl-4-piperidones in good yields <07EJO4376>. In a somewhat similar mode, the diastereoselective synthesis of cyclic (3-amino esters by an Sn2 substitution-cyclization of an iodo-a,(3-unsaturated ester with (.Sj-u-mcthy 1 benzylamine was described <07OBC3614>. A combination intramolecular Michael-type addition followed by retro-Michael elimination was exploited in the generation of a phosphoryl dihydropyridone intermediate in the synthesis of /m .v-2,6-disubstitutcd 1,2,5,6-tetrahydropyridines <07JOC2046>. 

A double iodoetherification of C2-symmetric acetals has been used for the desymmetrization of 1,6-dienes in an asymmetric total synthesis of rubrenolide (Equation 78) <2005AGE734>. Remarkably, four stereogenic centers have been installed in one reaction step. Stereoelectronic effects in the diastereoselective synthesis of 2,3,5-trisubstituted tetrahydrofurans via iodoetherification have been studied in detail, and I(2,4,6-collidine)2C104 proved to be an efficient reagent for highly stereoselective iodoetherifications <20010L429>. 

A diastereoselective formal addition of a 7ra i-2-(phenylthio)vmyl moiety to a-hydroxyhydrazones through a radical pathway is shown in Scheme 2.29. To overcome the lack of a viable intermolecular vinyl radical addition to C=N double bonds, not to mention a reaction proceeding with stereocontrol, this procedure employs a temporary silicon tether, which is used to hold the alkyne unit in place so that the vinyl radical addition could proceed intramolecularly. Thus, intermolecular addition of PhS" to the alkyne moiety in the chiral alkyne 161 leads to vinyl radical 163, which cyclizes in a 5-exo fashion, according to the Beckwith-Houk predictions, to give aminyl radical 164 with an a 7z-arrangement between the ether and the amino group. Radical reduction and removal of the silicon tether without prior isolation of the end product of the radical cyclization cascade, 165, yields the a-amino alcohol 162. This strategy, which could also be applied to the diastereoselective synthesis of polyhydroxylated amines (not shown), can be considered as synthetic equivalent of an acetaldehyde Mannich reaction with acyclic stereocontrol. 

This section covers the diastereoselective synthesis of ally lie alcohols or their derivatives (allylic esters, carbamates, phosphates or ethers) from allylic precursors with oxygen transfer and double-bond migration according to the following general schemes. 

Eventually, a breakthrough to a double diastereoselective synthesis of GDIBOA and GDIMBOA was found. The essential feature of this method consisted in using boron trifluoride etherate in excess (8-fold) rather than in catalytic amounts [133] (Fig. (18)). 

Moelm, D., Floerke, U., Risch, N. Fragmentation reactions of quatemized y-amino alcohols. Diastereoselective synthesis of highly functionalized oxetanes and unsaturated aldehydes and ketones with a (Z)-C C double bond. Eur. J. Org. Chem. 1998, 2185-2191. 

In Figure 17.23, transformation 96 constitutes a rotative sp chirostereogenesis that is diasterevectoselective and enantiofacioselective - manifested in the formation of four chiral diastereomers (596, 597, 598, and 599). The process may be considered a case of double diastereoselective synthesis. Finally, each of transformations 97 and 98 yields two astereomeric sets of diastereomeric pairs in the former case, all four components (602-605) are chiral in the latter transformation, one of the components (608) is achiral, the other three are chiral (609-611). The former transformation represents a composite case of rotative achirostereotopolysis and rotative nonstereotopomutation in contradistinction, the latter transformation is a composite case of nonrotative achirostereotopolysis and rotative nonstereotopomutation. Both transformations are subject to astereovectoselectivity and enantiofacioselectivity. 

A strategy developed by Tietze and coworkers early in his independent career involved the application of intramolecular or intermolecular inverse electron demand hetero-Diels-Alder reactions to iridoid total synthesis. The intermolecular [4+ 2]-cycloaddition of ethyl vinyl ether and unsaturated aldehyde 31 provided acetal 32, which underwent double bond isomerization to afford 33 (Scheme 1) An intramolecular variant of this reaction is discussed in detail later (Scheme 10). More recently, Jacobsen and Chavez extended this work with the enantio- and diastereoselective synthesis of a range of iridoid natural products. Utilizing tridentate Cr(III) catalyst 34, acetal 35 was prepared in 98% ee with good diastereoselectivity (Scheme 1)P... 

Very recently, the enantio- and diastereoselective synthesis of an S-shaped double azahelicene has been achieved via the gold-catalyzed sequential intramolecular alkyne hydroarylation (Scheme 21.51) [57]. 

SCHEME 21.51 Enantio- and diastereoselective synthesis of S-shaped double azahelicene. 

Gold-catalysed cycloisomerization of l,7-diyn-3,6-bis(propargyl carbonate)s provide for a diastereoselective synthesis of naphtho[ ]cyclobutenes by a cascade sequence involving gold-catalysed double [3,3]-rearrangement, 6 r-electrocyclic reaction, and a decarbonylative cyclization (Scheme 15). °... 

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