Following is one of the patent documents most requested by researchers using CAS electronic products.
|
CAS indexed 110 chemical substances from this document.
CAS subject entries for this document include: Aldol condensation; Aldol condensation catalysts; Cycloaddition reaction; and 21 additional concepts. | |
CAPLUS COPYRIGHT 2005 ACS on STN
| TITLE:
| Enantioselective transformations of .alpha.,.beta.-unsaturated aldehydes by a wide variety of reactions using imidazolidinone enantiomers as chiral organic catalysts |
| INVENTOR(S):
| MacMillan, David W. C. |
| PATENT ASSIGNEE(S):
| California Institute of Technology, USA |
| SOURCE:
| PCT Int. Appl., 67 pp. CODEN: PIXXD2 |
| LANGUAGE:
| English |
PATENT INFORMATION: PATENT NO. KIND DATE APPLICATION NO. DATE
--------------- ---- -------- -------------------- --------
WO 2003002491 A2 20030109 WO 2002-US20858 20020701
WO 2003002491 A3 20030626
W: AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, BZ, CA, CH, CN,
CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, ES, FI, GB, GD, GE, GH,
GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR,
LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NO, NZ, OM, PH,
PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TN, TR, TT, TZ,
UA, UG, US, UZ, VN, YU, ZA, ZM, ZW
RW: GH, GM, KE, LS, MW, MZ, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY,
KG, KZ, MD, RU, TJ, TM, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES,
FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE, SK, TR, BF, BJ, CF,
CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG
EP 1412335 A2 20040428 EP 2002-749735 20020701
R: AT, BE, CH, DE, DK, ES, FR, GB, GR, IT, LI, LU, NL, SE, MC, PT,
IE, SI, LT, LV, FI, RO, MK, CY, AL, TR, BG, CZ, EE, SK
ABSTRACT:
Nonmetallic org. catalysts are provided that facilitate the enantioselective reaction of .alpha.,.beta.-unsatd. aldehydes. The catalysts are chiral imidazolidinone compds. I or II, or their acid addn. salts, wherein, in one preferred embodiment, R1 is C1-C6 alkyl, R2 is tri(C1-C6 alkyl)substituted Me, R3 and R4 are H, and R5 is Ph optionally substituted with 1 or 2 substituents selected from the group consisting of halo, OH, and C1-C6 alkyl. More broadly, compds. I and II and their acid addn. salts are claimed, wherein R1 is (un)substituted (hetero)hydrocarbyl, R2 is trihydrocarbylmethyl(alkyl), R3 and R4 are H, halo, OH, or (un)substituted (hetero)hydrocarbyl, and R5 is an (un)substituted cyclic group. The chiral imidazolidinones are useful in catalyzing a wide variety of reactions, including Diels-Alder and other cycloaddn. reactions, Friedel-Crafts alkylation reactions of aroms. and heteroaroms., and various Michael addns. The catalysis involves lowering of the LUMO of the carbon-carbon double bond within the aldehyde. These catalysts avoid the problems assocd. with traditional metal catalysts, are readily synthesized from inexpensive, com. available reagents, are compatible with aerobic conditions, and provide products in excellent yields with a high level of enantioselectivity. For instance, (S)-phenylalanine Me ester was amidated with ethanolic MeNH2 to give the N-methylamide (82%), which was cyclocondensed with Me3CCHO in THF in the presence of FeCl3 and 4.ANG. mol. sieves, to give cis-epimeric catalyst III in 23% yield and 99% enantiomeric excess (ee), plus the trans epimer, sepd. as its HCl salt. The trans epimer salt was recycled to give addnl. III in 22% yield. Use of III and HCl (0.10 mmol each) as the catalyst for Diels-Alder cycloaddn. of 1.0 mmol (E)-crotonaldehyde with 4.0 mmol cyclopentadiene at -60.degree. in CHCl3 over 4.5 days gave the (1S,2R,3S,4R)-enantiomeric adduct IV in 80% yield. This product showed a 5.0:1.0 endo/exo ratio, and 93% ee for the exo isomer. Addnl. reactions included an intramol. Diels-Alder (85% yield, 99:1 endo/exo, endo 93% ee), a nitrone cycloaddn. (96% yield, 150:1 endo/exo, endo 98% ee), a Friedel-Crafts alkylation (96% yield, 95% ee), similar heterocycle alkylations (78-87% yield, 90-95% ee), and various Michael-type addns. (69-70% yield, 84-90% ee). The reaction was applied to the enantioselective construction of a pyrroloindoline alkaloid core V from 1-allyl-N-BOC-tryptamine and acrolein, using III and p-MeC6H4SO3H as catalyst, in 91% yield and 93% ee. Thus, natural product applications include flustramine B, fructigenine C, amauromine, urochordamine A, and (-)-chimonanthine. The study included the effects of acid addn. salt on the catalyst, and both aldehyde and indole substitution on indole alkylations.
Updated 5/8/2007 10:59:39 AM
