Asymmetric Homoaldol Reactions with Cyclohex‐2‐enyl N,N‐Diisopropylcarbamate: Kinetic Resolution, Elucidation of the Stereochemical Course and Applications in the Synthesis of Hexahydroisobenzofuran‐4‐(1H)‐ones

Abstract

Enantio-enriched cyclohex-2-enyl N,N-diisopropylcarbamate (5) is stereospecifically deprotonated by sec-butyllithium/(-)-sparteine (9) to form the configurationally stable lithium complex 7·9. A kinetic resolution of rac-5 by n-butyllithium/(-)-sparteine (9) yielded (R)-5 with up to 99 % ee. Electrophilic substitution with tin electrophiles proceeds in a anti-S E Ј fashion as shown by chemical correlations. The synthesized allylstannanes 10 undergo a highly stereospecific

Asymmetrische Totalsynthese und Festkörperstruktur des marinen cytotoxischen Diterpens (+)‐Vigulariol

“…= 83:17). [26] Die BF 3 -vermittelte Cyclokondensation [13] [27] Zwar hatten Crimmins et al [28] demonstriert, dass Oxacyclononene durch Ringschlussmetathese zugänglich sind, allerdings schien die Cyclisierung von 18 problematisch zu sein. Die Versuche von Overman und Joe [29] sowie Jung und Pontillo [30] zum Aufbau ähnlicher Di-und Tricyclen durch Metathese scheiterten.…”

Stereoselective Synthesis of Hexahydroisobenzofuran‐4(1H)‐ones from Chiral Substituted Cyclohex‐2‐enyl Carbamates via Asymmetric Homoaldol Reaction and THF Cyclocondensation

“…aldehyde 34 and BF 3 ·OEt 2 to yield the diastereomerically pure bicycles 35 in good yields (Scheme 6). As observed with unsubstituted cyclohex-2-enyl carbamate the syn configuration of the homoaldol product leads to all-cis-configured hexahydroisobenzofuran-4(1H)-ones, [5] which is not influenced by substituents on the cyclohexene ring. The configuration of the tetrahydrofuran moiety of 35b (R = 2-naphthyl, RЈ = Ph) was determined by nOe-experiments.…”

“…Interestingly, the reaction of the six-membered cyclic trichlorotitaniumallyl carbamate with aldehydes afforded exclusively syn-homoaldol products. [5,23] …”

“…[9] (5R)-cis-Carveol (6) is readily available by reduction of commerically available (R)-(-)-carvone (5). [10] The cis-isomer 2 (99 % ee) was isolated after carbamoylation and chromatography.…”

“…(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) tures have recently been published. [4] In the preceeding paper [5] we reported a highly stereocontrolled synthesis of simpler all-cis-hexahydroisobenzo-furan-4(1H)-ones which is based on the asymmetric deprotonation [6] of cyclohex-2-enyl N,N-diisopropylcarbamate, its homoaldol reaction with aldehydes, [7] and subsequent cyclocondensation with aldehydes [8] (Figure 1). One crucial feature is the question whether it is possible to construct a 1,3-cis-3,3a-trans-3a,7a-cis-tetrasubstituted hexahydroisobenzofuran-4(1H)-one instead of the all-cissubstituted tetrahydrofuran moiety.…”