Aldehyde Enol Esters as Novel Chain Terminators in Cationic Olefin Cyclizations

Abstract

1 1.IV.88) ~ ~ ~ ~ ~~~ ~ Citronella1(1) has been transformed into enol acetates 2 which have been cyclized with various Lewis and Briin.rlrd acids to dihydrocyclocitral (4). Application of this methodology to the synthesis of mono-and bicyclic ring systems has been examined.Introduction. -Cationic olefin cyclizations have been widely utilized for the synthesis of terpenes and other naturally occurring ring systems. Cyclizations initiated by protonation of trisubstituted double bonds have been terminated by a variety of functional groups such as alkyl-, aryl-, carboxyl-, 0-, F-, or (trialkylsily1)-substituted double bonds or alkynes [I]. In this communication, we report the use of aldehyde enol acetates as cationic cyclization terminators for the preparation of monocyclic and bicyclic terpenoids and similar ring systems.Aldehyde enol esters are attractive as cationic olefin cyclization terminators for several reasons. Aldehydes are easily, under mild conditions, transformed into enol esters, normally as (E/Z)-isomeric mixtures [2]. Ketones can also be transformed into enol esters, although under more stringent conditions, and be employed in cationic cyclization reactions [3]. However, regioselective ketone enol ester formation is often difficult to obtain. Cyclization of an aldehyde enol ester followed by aqueous workup again yields an aldehyde, which can be used in further synthetic manipulations. Thus, this scheme permits the formation of a C-C bond via cationic cyclization with retention of a heterofunctionality in a predictable manner.Results and Discussion. -Treatment of citronella1 (1) with a mixture of Ac,O, Et,N, and KOAc at 120" for 4 h followed by distillation furnished routinely enol acetates 2 ( ( E / Z ) 2:l) in 80% yield (cf Scheme). A third product identified as the diacetate 3 was also formed in 3-6% yield. Enol acetates 2 underwent acid-induced cyclization to dihydrocyclocitral(4) with a variety of Lewis and Bronsted acids (cf Table).The similar reactivity of Lewis and Bronsted acids was at first surprising until we observed that reactions with Lewis acids were much faster in the presence of a small amount of H,02). Under stringently dry conditions, the Lewis-acid-catalysed cyclizations were much slower and lower yielding. Catalytic amounts of Lewis acid as opposed to ')

Olfactory study on optically active citronellyl derivatives

“…The (3S)-13 (100 g, 0.60 mol) was added dropwise to Vitride ® (310 g, 1.07 mol) in toluene (400 ml) at rt for 2 h, followed by stirring for 12 h to complete the reaction. The mixture was worked up as usual, followed by distillation to yield the (3S)-14: 84.0 g, 83.0%, bp 125.5-126°C/12 mmHg; GC, 99.8%, 98%ee, (14), 109 (5), 107 (17), 96 (12), 82 (100), 69 (38), 66 (44), 43 (24).…”

“…HCHO (35%, 1.1 eq.) at 85°C in yield of 78%, and subsequent reduction of 13 by Vitride™ afforded an enantiomeric pair of α-methylene citronellol (14) in 83% yield. On the other hand, the chiral citronellyl ethyl oxalate (15) was synthesized by PTSA-catalysed ester-exchange reaction of diethyl oxalate and the chiral 4 in yield of 82.4% (Scheme 4).…”

Synthesis of Citronellal by RhI-Catalysed Asymmetric Isomerization ofN,N-Diethyl-Substituted Geranyl- and Nerylamines or Geraniol and Nerol in the Presence of Chiral Diphosphino Ligands, under Homogeneous and Supported Conditions

“…of the ligand) for both diethylgeranylamine ((E)-1) [21] and diethylnerylamine ((Z)-1) [22] 7 ) when compared to (R)-5 used under homogeneous conditions (see Table 1, Entries 1 and 2). The ratio (R)-6/(E)-1 could even be decreased to 0.1 mol-% without affecting either the conversion or the enantioselectivity 8 ). Thus, hydrolysis of the transient enamine (S)-3 and bulb-to-bulb distillation afforded (S)-4 in 98% e.e.…”

“…84 (2001) 2328 ) The enantioselectivity was determined directly by chiral capillary GC analysis (50% 2,3-di-O-acetyl-6-O-[(tert-butyl)dimethylsilyl]-b-cyclodextrin (Brechbuehler SA), 25 m, 0.25 mm) of the enamine (608, 1.58/ min, 1008 for 10 min, 70 KPa iso, 0.92 ml/min, 25.2 cm/s He t R 32.96 min for (S)-3 and 33.33 min for (R)-3) or of citronellal (1008 for 36 min, 158/min, 1508 for 5 min, 75 KPa for 36 min, 20 KPa/min, 170 KPa for 3 min, 0.8 ml/min, 24.9 cm/s He; t R 33.1 min for (S)-4 and 34.1 min for (R)-4)[24]. Standard error AE 1%.…”

Convenient preparation of carbonyl compounds from 1,2-diols utilizing Mitsunobu conditions

“…Compounds 12b and 13b showed identical properties to those reported in the literature. 16,17 In summary, this reaction, which takes place under neutral conditions, constitutes a mild alternative for preparing carbonyl derivatives from alkenes.…”