Dioxolane enantiomeric synthesis

In Entry 11 the dienophile is an a-methylene lactam. As noted for this class of dienophiles, the stereoselectivity results from preferred exo addition (see p. 471). The reaction in Entry 12 was used in an enantiospecific synthesis of estrone. The dienophile was used in enantiomerically pure form and the dioxolane ring imparts a high facial selectivity to the dienophile. The reaction occurs through an endo TS. 

Enantiomerically pure tetrahydro-l//-pyrrolo[2, l -acrylamides derived from proline (see Section 11.11.7.4), are versatile intermediates for the synthesis of natural products or drugs. Compound 86a was submitted to debromination with Bu3SnH followed by ring opening in KOH and further reduction with BHj to give diol 89 that was then easily transformed into (A)-4-(2,2,4-trimethyl-l,3-dioxolan-4-yl)-lT>utanol 90, a key intermediate for )-frontalin, <2002TA155>,... 

Pedro et al. reported the enantioselective synthesis of (,S )-3-hydroxy-3-phenyl-3,4-d i hydroquinol i n - 2 (1 /f)-o n c through an extension of their methodology for the diastereoselective benzylation of (.S )-mandelic acid <07S108>. The reaction commences with the benzylation of dioxolane 90 with substituted o-nitrobenzyl bromides 91 followed by the cyclization of adduct 92 resulting in enantiomerically pure dihydroquinolines 93 in good to high yields. 

The highly diastereoselective cyclopropanation of an a.jS-dehydroamino acid derivative bearing a (lS)-l,2-dioxolane group as inducing substituent is achieved by treatment with diazomethanc followed by photolysis. The chiral substituent is transformed into an ethenyl group, thus allowing synthesis of an enantiomerically pure (lS,27 )-l-amino-2-ethenylcyclo-propanecarboxylate derivative103. 

Stereoselective, radical bromination of cyclic acetals with /V-bromosuccinimide is one of the steps in the synthesis of enantiomerically pure derivatives of pyruvic acid103. Asymmetric bromination in the a-position of dioxolanes is used for the preparation of optically active carbonyl cotnpunds1"4 The mechanism involves bromination of the low concentration ring-opened enols106. 

A parallel sequence of reactions, this time using the enantiomeric (i )-303 epoxide, leads to 1,3-polyols containing a, >-syn-lf,5-anti-Xno unit (Scheme 89) [144]. The key reduction of 608 as well as the iterative ketone reaction later in the synthesis requires lithium tri- er/-butoxyaluminohydride-lithium iodide to provide high syn selectivity (approximately 95 5) with respect to the dioxolane ring. 

Homoallylic alcohols were directly prepared from aromatic acetals and dioxolanes (> 80%) using a Barbier-type allylation, Zn/allyl bromide/NH4Cl, in the presence of j3-CD in water at 50 °C (Figure 4.8). The synthesis of enantiomerically enriched homoallylic alcohols is an important goal in organic synthesis. An enantioselective metal-mediated allylation of substitnted benzaldehydes with jS-CD was achieved. The reaction proceeds in short reaction times (Ih) at room temperatnre. The homoallylic alcohols are obtained in moderate yields with up to 93% enantioexcess. 

P. Van Roey, and R. F. Schinazi, Asymmetric synthesis of enantiomerically pure (-)-(rR,4 R)-dioxolane-thymine and its anti-HTV activity. Tetrahedron Lett. 32 3791 (1991). 

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