Citronellal, cyclization

P-citronellene 605 f 612 (/Q-citronellic acid 232, 235 (/ )-citronellol 360 Claisen rearrangement 17, 87, 90, 137 f., 140, 142, 194 -, Johnson ortho ester variant see Johnson ortho ester Claisen rearrangement cobalt-mediated cyclization... 

The tandem-Knoevenagel-ene reaction is a powerful tool to synthesize five-and six-membered carbocycles.2 5 The process is exemplified by the diastereoselective synthesis of 4a. Compound 4a has been obtained In both enantiomeric forms and as a racemate according to the procedure described here. The sequence includes the Knoevenagel reaction of citronellal, 1, and dimethyl malonate, 2, followed by the intramolecular ene cyclization of the chiral 1,7-diene 3 to yield the trans 1,2-disubstituted products 4a and 4b. Whereas the thermal cyclization of 3 at 160°C provides 4a and 4 b in a ratio of only 89.7 10.3, the Lewis acid... 

This methodology has been extended by the same author to include carbonyl-ene reactions [37]. The cyclization of (+)-citronellal (19) to pulegols 20 and 21 is faster... 

Cyclization of citronellal in the presence of KSF catalyst [93]. Reaction conditions reflux, CC14 as solvent, single-mode reactor,... 

Isomerization of allylic amines is another example of the application of the BINAP complex. Rh BINAP complex catalyzes the isomerization of N,N-diethylnerylamine 40 generated from myrcene 39 with 76-96% optical yield. Compound (R)-citronellal (R)-42. prepared through hydrolysis of (R)-41, is then cyclized by zinc bromide treatment.49 Catalytic hydrogenation then completes the synthesis of (—)-menthol. This enantioselective catalysis allows the annual production of about 1500 tons of menthol and other terpenic substances by Takasago International Corporation.50... 

Ene catalyst.1 FeCl3 is superior to ZnBr2 or alkylaluminum halides as a catalyst for ene cyclization of the chiral 1,7-diene 1, the Knoevenagel adduct from citronellal and dimethyl malonate. Thermal cyclization provides the 1,2-trans-substituted... 

Key steps are the enantioselective isomerization of diethylgeranylamine and the diastereoselective ring closure of (+)-citronellal to (—)-isopulegol. Mechanistically, the isomerization is well understood. As to the cyclization, notably, the most stable (all-equatorial) diastereoisomer is formed. 

The intramolecular carbonyl ene reaction is a useful way to generate a C-C bond and has been well studied [49-52]. Of particular interest is the cyclization of citronellal to yield isopulegol, an important intermediate in an industrial synthesis... 

Aggarwal VK, Vennall GP, Davey PN, Newman C (1998) Scandium trifluoromethane-sulfonate, an efficient catalyst for the intermolecular carbonyl-ene reaction and the intramolecular cyclization of citronellal. Tetrahedron Lett 39 1997-2000... 

R = vinyl or ethynyl) predominates (c/. Vol. 1, p. 36 Vol. 2, p. 35). Base treatment of a 2-alkoxypyridinium tosylate of nerol gives expected e.g. limonene 82%) cyclic hydrocarbons whereas the corresponding geraniol salt yields similar amounts of cyclic and acyclic hydrocarbons. SnCU-catalysed cyclization of the N-benzylimine derived from R-(+)-citronellal yields the expected menthylamines after catalytic hydrogenation. ... 

Hydrolysis of the enamine 14 furnishes citronellal (15) in high optical purity (ca. 99% ee) which gives 17 via ene cyclization with zinc bromide as catalyst. The diastereoselectivity of this step is the result of simple diastereoselection in a trans-decalin-like transition state 16. Catalytic hydrogenation converts the olefin 17 into (—)-menthol (18). Despite its elegance this novel route has not been able to replace the older resolution-based procedure described earlier in this section. 

Isopulegol can be isolated from this mixture and hydrogenated to (-)-menthol. The remaining isopulegol stereoisomers can be partly reconverted into (+)-citronellal by pyrolytic cleavage and reused in the cyclization procedure [79]. 

The isopulegols occur in a large number of essential oils, often in optically active or partly racemic form. Since citronellal readily cyclizes to isopulegol, the latter occurs frequently in citronellal-containing essential oils, in which it is formed during the recovery of the oil. 

In a subsequent study, however, Whittaker and co-workers803 showed that the product formed from geraniol, in fact, is the isomeric bicychc ether 198. It was also shown that cyclization of citronellal in HSO3F— SO2 at 78°C affords pulegol and neoisopulegol that is, the transformation parallels closely the reaction in normal acids.804... 

EG acid-catalyzed cyclization of citronellal 70 in a CH2Cl2,/THF(7/1)—E NOTs/ LiC104—(Pt) system gives a 91% yield of the cyclized products 71, a precursor for the synthesis of menthofuran 73 via the ene-type chlorination product 72 (Scheme 3-26)... 

Menthol is used in many consumer products, such as toothpaste, chewing gum, cigarettes, and pharmaceutical products, with an estimated worldwide consumption estimated at 4500 tons per year (Chapter 31)4143 (-(-Menthol (22) is manufactured by Takasago Co. from myrcene (23), which is available from the cracking of inexpensive P-pinene (Scheme 12.6)4244 The key step in the process is the asymmetric isomerization of /V,/V-diethylgcranylarninc (24) catalyzed by either [Rh(L2)(5 -BINAP)]+BF f (where L is diene or solvent) or Rh(.S -BINAP)2]+BF f to the diethyl enamine intermediate 25 in 96-99% ee.3645 Citronellal (26) is obtained in 100% ee after hydrolysis of the enamine intermediate natural citronellal has an optical purity of 80%.35 A stereospecific acid-catalyzed cyclization followed by reduction produces 22.42... 

The simplicity and power of this reaction is illustrated by the spontaneous cyclization of the derivative 7, formed from the condensation of (K)-citronellal (8) and 5-//-pen(yl-1,3-cyclohexanedi-one, which occurs with complete stereochemical control (Scheme 26.7).235... 

Cationic olefin cyclization of aldehyde enol acetates.1 The enol acetate (2) of citronellal (1) undergoes cyclization to dihydrocyclocitral (3) in the presence of... 

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