Intramolecular diastereoselectivity

Intramolecular diastereoselective alkylation of the exocyclic enolate derived from compound 6 results in cyclization yielding bicyclic 7 in 94%. 

An intramolecular diastereoselective Refor-matsky-type aldol approach was demonstrated by Taylor et al. [47] with an Sm(II)-mediated cy-clization of the chiral bromoacetate 60, resulting in lactone 61, also an intermediate in the synthesis of Schinzer s building block 7. The alcohol oxidation state at C5 in 61 avoided retro-reaction and at the same time was used for induction, with the absolute stereochemistry originating from enzymatic resolution (Scheme II). Direct re.solution of racemic C3 alcohol was also tried with an esterase adapted by directed evolution [48]. In other, somewhat more lengthy routes to CI-C6 building blocks, Shibasaki et al. used a catalytic asymmetric aldol reaction with heterobimetallic asymmetric catalysts [49], and Kalesse et al. used a Sharpless asymmetric epoxidation [50]. 

Auxiliary-Controlled Intramolecular Diastereoselective Conjugate Addition of /V-Nucleophiles... 

I.2.I.2. Substrate-Controlled Intramolecular Diastereoselective Conjugate Addition to Chiral a, -Unsaturated Compounds... 

The Kobayashi group has observed the intramolecular diastereoselective spirocyclization of racemic 2-haloindoles bearing a C3-tethered allylic alcohol [71, 72]. For example, CuCl-catalyzed intramolecular Ullmann coupling of 117 followed by spontaneous Claisen rearrangement of the intermediate pyranoindole 118 afforded, in a one-pot synthesis, the all-carbon quaternary center of spiro-oxindole 119 in 95% de (Scheme 31). The methodology has been extended to the synthesis of hexahydropyrroloindoles, e.g., ( )-debromoflustramine B and E. 

An intramolecular diastereoselective cascade cyclization reaction of salen with POCI3, gave rise to a new compound 212 that contains two new stereogenic phosphorus atoms and two new stereogenic carbon atoms in the oxadiazepine ring (14PS226). The polycycHc compound, bis(chlorophosphorylated) decahydro-2,4-di(2-hydroxyphenyl)benzo[chiral carbon atoms in the -position to phosphorus. 

Diels-Alder precursor 1143 was accessible from aldehyde 1140, dienylpho-sphonate 1141, and benzoyl pyrrolidinone 1142 in 18 steps. Elimination of the phenylselenyl group generated a double bond, which was subjected to an intramolecular, diastereoselective Diels-Alder reaction at elevated temperatures to yield... 

Platinum catalysts of the preceding section activate only the nucleophile (a secondary phosphine), which then reacts with the electrophile (an activated alkene). There are, however, interesting examples of lanthanide complexes activating both the nucleophile and the electrophile towards intramolecular diastereoselective hydrophosphination/cyclisations. In 2000 Marks and co-workers found that certain lanthanide complexes catalyse the intramolecular hydrophosphination of alkenes and alkynes (Scheme 6.13). 

Paderes and Chemler developed an intramolecular diastereoselective aminooxygenation of unactivated alkenes to pyrrolidines. Cu(EH)2/02 catalytic system could lead to 2,5-cis- and 2,5-fra s-pyrrolidines formation from a-substituted 4-pentenylsulfonamides in good to excellent yields and >20 1 selectivity. For P- and /-substituted 4-pentenylsulfonamides, Cu(OTf)2-bis(oxazoline) with O2 catalytic system could give higher diastereoselectivities. Furthermore, enantioselective desymmetrization could be achieved (up to 98% ee) with /l-allyl-4-pentenylsulfonamide [26] (Scheme 8.13). 

Scheme 8.13 Intramolecular diastereoselective aminooxygenation of unactivated alkenes to pyrrolidines.

Clusiacyclol A 171 and B 172 were isolated from the fruit extract of Clusia multiflora in 1994 by Monache and coworkers [90]. The compounds with oxacyclobutaindan core units have been synthesized previously by using intramolecular [2-1-2] photochemical [73,77,91] or acid-catalyzed cationic [75] cycloaddition reactions of various suitably substituted benzopyrans. Argade and coworkers have demonstrated a simple and efficient phenol-directed intramolecular diastereoselective dipolar thermal/base-catalyzed [2-1-2] cycloaddition approach to novel biologically important natural and synthetic benzopyran systems (Scheme 12.41) [92]. The trihydroxybenzophenone 167 was synthesized with high yield from trimethoxybenzene 166 via... 

Yamamoto has reported the use of an intramolecular diastereoselective allylation reaction in a synthesis of hemibrevetoxin (Equation 10) [94]. Treatment of 124 with BF, effects diastereoselective C-C bond formation to afford the key oxepane ring in 125 in 94% yield. 

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