Camphor conjugate additions

Cul, methyllithium, and a camphor-derived /3-amino alcohol (239). Reaction of methylmagnesium iodide and benzylideneacetone in the presence of a small amount of a chiral Cu(I) thiolate complex gives the conjugate addition product in 57% ee (240). 

Tetrakis(triphenylphosphine)-palladium(O), 289 Conjugate addition reactions (IS, 2S)-2-Amino-3-methoxy-1 -phenyl-1-propanol, 17 Camphor, 61... 

Asymmetric conjugate addition of RiCuLij The chiral crotonyl ester 1, prepared from (+ )-camphor by addition of 1-naphthylmagnesium bromide followed by esterification with crotonic acid, undergoes conjugate addition with BuaCuLi at -25° to give the adduct 2 in 95% de. Reduction of 2 with LiAUtj gives (S)-3-... 

The asymmetric conjugate addition of diethylzinc with chalcone was also catalyzed by nickel and cobalt complex (Eq. (12.31)) [71]. A catalytic process was achieved by using a combination of 17 mol% of an aminoalcohol 34 and nickel acetylacetonate in the reaction of diethylzinc and chalcone to provide the product in 90% ee [72, 73]. Proline-derived chiral diamine 35 was also effective, giving 82% ee [74]. Camphor-derived tridentate aminoalcohol 36 also catalyzes the conjugate addition reaction of diethylzinc in the presence of nickel acetylacetonate to afford the product in 83% ee [75]. Similarly, the ligand 37-cobalt acetylacetonate complex catalyzes the reaction to afford the product in 83% ee [76]. 

The camphor-derived tridentate amino alcohol 32 (Scheme 17) also catalyzes the conjugate addition reaction of diethylzinc in the presence of nickel acetylac-etonate to afford the product in 83% ee [75]. Similarly the Hgand 33-cobalt acety-lacetonate complex catalyzes the reaction to afford the product in 83% ee [76]. 

Optically pure sultams have been used by Oppolzer as chiral auxiliaries in various asymmetric transformations, including Diels-Alder reaction, aldoliza-tion, conjugate addition, his-hydroxylation, and catalytic hydrogenation [42,43]. In the literature, the most commonly used chiral sultam is derived from camphor (Oppolzer s sultam). The ready access to 80 and other chiral sultams from the Diels-Alder cycloadducts could further expand the scope of their use as chiral auxiliaries in asymmetric synthesis. 

The synthesis of the C1-C7 fragment, which corresponds to the lactone, starts with the homoallylic alcohol 2 which was prepared from 1. The existing stereocenter and the conjugate addition method of Evans [21] allow the control of the C5 stereocenter. The homoallylic alcohol 2 was oxidatively cleaved and homologated to the trans enoate 3 by a Wittig olefination. Treatment of 3 with benzaldehyde and a catalytic amount of KHMDS provided acetal 4. The internal Michael addition of the hemiacetal intermediate proceeds with complete stereoselectivity [22]. After deprotection and oxidation, the corresponding aldehyde was treated with Amberlyst-15 and then with camphor sulfonic acid (CSA), to yield pyrane 5 as a mixture of (3- and a-anomers (1.8/1). This compound was converted to the thiophenyl acetal 6 (4 steps) as this compound can be hydrolyzed later under mild conditions (Hg +) with subsequent oxidation of the lactol to the desired lactone. Compound 6 represents the C1-C7 fragment of discodermolide (Scheme 1). 

Other auxiliaries are also used, and the choice of auxiliary may depend not only on the selectivity of the reaction under investigation but also on the physical properties of the products. The camphor-based auxiliary of Oppolzer is reputed to confer crystallinity on its derivatives, while the pseudoephedrine auxiliary of Myers is cheap, readily available, and very easy to introduce. More bulky auxiliaries such as 8-phenylmenthol work well where control over long-range interactions, such as conjugate additions, are required. 

Synthesis of Chiral Auxiliaries. Their availability and crystalline nature has made camphor derivatives the precursors of choice for the design and synthesis of chiral auxiliaries. 10-Camphorsulfonyl chloride is the starting material for the synthesis of chiral auxiliaries (9)-(12) (eq 2). Sulfonamides (9) and (10) have been used as chiral auxiliaries in a number of reactions, e.g. the Lewis acid-catalyzed Diels-Alder reaction, the [3 + 2] cycloaddition of a nitrile oxide to an acrylate, and the stereoselective conjugate addition reaction of organocopper reagents to ci ,)3-unsaturated esters. ... 

The structural motifs of some excellent chiral crown ethers have been derived from easily accessible natural products. For example, a (+)-camphor-based chiral aza-crown ether 7 was developed and successfully apphed in asymmetric conjugate addition by Brunet [11]. The use of D-glucose-based crown ethers 8 and 9 as chiral phase-transfer catalysts has been intensively studied by Bako and colleagues in the asymmetric Michael addition [12], Darzens condensation [13], and epoxidation [14]. Another carbohydrate-derived chiral crown ether 10 was prepared from chiro-inositol by Aldyama and coworkers, which successfully enabled the enantioselective conjugate addition of N-(diphenylmethylene) glycine tert-butyl ester to several electrophiles [15]. 

Parameters such as, synthesis medium (HCl, camphor sulfonic add (CSA) or dodecylbenzene sulfonic acid (DBSA)), molar ratio aniline/oxidant, method for oxidant addition, temperature, polymerization duration, dedoping conditions will have effects on polymer properties in terms of yield, chain length, effective conjugation, defects rate, and electrical properties. Temperature was kept to 0 C, -30 C or -40 C and reactions were stopped after various durations in order to control the molecular weight of samples. Polymerization durations were varied from 1 hour to 5 days and depended on the reaction temperature. The inherent viscosities of the polyanilines (Pani) were determined at 25 °C in 0.1%w solutions in concentrated sulfuric acid (95 %), using an Ubbelohde viscometer. For instance, high viscosity samples (1.4 dl/g) were obtained after 3 days at -40 °C vsMe low viscosity samples (0.6 dl/g) were obtained after 1 hour at 0 A relationship was found between polymerization duration and inherent viscosity for polymers synthesized at low temperature (- 40 °C). Inherent viscosity increases from 0.6 to 1.4 when duration of polymerization increases from one to five days. In the case of synthesis at 0°C no correlation was obtained between duration of polymerization and inherent viscosity. A careful control of other parameters (synthesis medium, molar ratio aniline/oxidant, method for oxidant addition) have permitted to get samples with inlierent viscosities ranging from 0.55 to 2.1 dl/g in a reproducible way. 

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