Brown allylation

The powerful directing effect of bis(isopinocampheyl) allylic boranes has been put to great use in the context of several applications of double diaster-ereoselective allylations in the total synthesis of natural products. As discussed in a previous section, the Brown allylation can be exploited to overcome the stereodirecting effect of chiral a-stereogenic aldehydes, including a-aUcoxy substituted ones. Thus, the simple allylation of aldehyde 154 provides as major product the desired diastereomer needed towards a total synthesis of brasilenyne (Scheme 14). The yield and stereoselectivity is even increased to over 97 3 under the low-temperature, magnesium-free conditions described before. 

The enantiomerically-pure intermediate 1 was prepared from the dioxolanone 4, available in three steps from L-malic acid. Lewis acid-mediated homologation converted 4, a 4 1 mixture of diastereomers, into 5 as a single diastereomer. After establishment of the alkenyl iodide, it necessary to maintain the lactone in its open form. A solution was found in the formation of the Weinreb amide. The final stereogenic center was established by Brown allylation of the derived aldehyde. The alkene metathesis to form 1 was carried out with the commercially-available Schrock Mo catalyst. The authors did not comment on the relative efficacy of alternative alkene metathesis catalysts. 

In the synthesis of a library of (+)-murisolin (39) and its 15 other stereoisomers, Curran and others used Brown allylation strategy to obtain the four diastere-oisomers of the homoallylic alcohol 4019 (Scheme 3.1p). Thus, the homoallylic alcohol (S,S )-40 was prepared in 95% ee from allylborane reagent l35 and corresponding aldehyde. By using the Mitsunobu reaction, (R,S )-40 was obtained. Similarly, (R,R)-40 was synthesized via the enantiomeric borane reagent d35... 

Scheme 4.5 Brown allylation using a chiral reagent for asymmetric addition to aldehydes...

Somfai s group demonstrated the use of a Lil-promoted vinylaziridine-3-pyrroline rearrangement in the formal synthesis of the antibiotic (-)-anisontycia The commercially available 2-(4-methoxyphenyl)acetaldehyde 43 was subjected to Brown allylation followed by aminolysis of the resulting chlorohydrin to afford the enantioenriched aminoalcohol 44 f Scheme 11.34). The enantiopure cis-vinylaziridine 45 was then prepared by O- and N-tosylation of the chiral aminoalcohol followed by KOH-promoted ring closure. Microwave-assisted rearrangement of vinylaziridine 45 using Lil as an additive afforded enantioenriched 3-pyrroline 46 in excellent yield, and this was converted to the natural product in several steps tScheme 11.34T ... 

Aldehyde 73 was prepared from aldehyde 70 using a Brown Allylation to control absolute stereochemistry in the preparation of 72. Bromide 68 was prepared using a Sharpless epoxidation to control absolute stereochemistry. Conversion of 73 to the corresponding enolate, alkylation with 68, and addition of more LDA to generate a new enolate (74) gave a reasonable yield of 75 (see Histrionicotoxin-8/9). 

The third component of (+)-superstolide A 3, the phosphonium salt 21, was assembled by Brown allylation of the aldehyde 15, to give 17. Protecting group interchange followed by ozonolysis delivered 18, which via Still-Gennari homologation was carried on to 21. Condensation with the fourth component, the aldehyde 22, and esterification with 14 then gave 1. 

Allyl bromide, purchased from Aldrich Chemical Company, Inc, is distilled and stored in a brown bottle away from light. 

Few other reactions of series of substituted pyridines have been investigated extensively. Dondoni, Modena, and Todesco have measured the rate of N-oxidation of a limited series of pyridines and found a good correlation with normal u-values with a p-value of — 2.23. The A-alkylation of pyridines with alkyl iodides in nitrobenzene has been studied by Brown and Cahn and by Clarke and Rothwell. Unfortunately, the only data available are for the parent compound and for alkyl derivatives, and, since the a-values for the various alkyl groups in a given position are substantially constant, this leaves a correlation of only three independent points. However, the rates of A-alkylation of the j8- and y-alkyl derivatives are so nearly equal that it appears as if no correlation existed. Clarke and Rothwell have also studied the alkylation with allyl bromide in nitromethane at various temperatures, and in this case a more extensive series is available. The authors state that no overall Hammett correlation is obtained however, the j8-substituted derivatives fall on one straight line and the y-derivatives on another one with a different slope. The data are shown in Fig. 2. The line for the j8-compounds, p = — 2.53 0.31, r = 0.95, is seen not to be very good the line for the y-derivatives, p = — 1.42 0.06, r = 0.99, is much more satisfactory. It does not seem likely that the discrepancy is due to the intervention of resonance effects, since in this case one would expect the correlation for the y-derivatives to be poorer than that for the j8-analogs. More extensive studies with a wider variety of substituents would seem very desirable. 

More recently, Brown and Fallis138 have described a similar epimerization of bicyclic and allylic tertiary alcohols, such as, for example, the epimerization of the endo alcohol 78 to its exo epimer 79 (equation 36). An exo-to-endo ratio of 8 to 1 was obtained in this case. 

For reviews, see Hoffmann, R.W. Niel, G. Schlapbach, A. Pure Appl. Chem., 1990, 62 1993 Pelter, A. Smith, K. Brown, H.C. Borane Reagents Academic Press NY, 1988, p 310. For a review of allylic boranes, see Bubnov, Yu.N. Pure Appl. Chem., 1987, 21, 89, For an example that proceeds with asymmetric induction, see Buynak, J.D. Geng, B Uang, S. Strickland, J.B. Tetrahedron Lett., 1994, 35, 985. 

In contrast to the Johnson s D —> A-ring construction approach, Brown devised an A —> D-ring construction approach [22]. Starting from Wieland-Miescher ketone (30), a common source of the A, B-rings in the de novo synthesis of steroids, the C-ring was introduced via hydrazone allylation, ozonolysis, aldol condensation, and olefin isomerization (31 > 32). The D-ring was assembled by a reductive alkylation... 

As practiced in the preceding syntheses by Evans and Nishiyama and Yamamura, the A-ring fragment 43 is formed through substrate-directed vinylogous aldol reaction of the Brassard-type diene 19 and the chiral aldehyde 42, which is prepared using Brown s protocols for enantioselective allylation [53], followed by hydroxy-directed nnn-diastereoselective reduction of the C3 ketone (Me4NB(OAc)3H) [41],... 

Palladium-catalyzed oxidation of 1,4-dienes has also been reported. Thus, Brown and Davidson28 obtained the 1,3-diacetate 25 from oxidation of 1,4-cyclohexadiene by ben-zoquinone in acetic acid with palladium acetate as the catalyst (Scheme 3). Presumably the reaction proceeds via acetoxypalladation-isomerization to give a rr-allyl intermediate, which subsequently undergoes nucleophilic attack by acetate. This principle, i.e. rearrangement of a (allyl)palladium complex, has been applied in nonoxidative palladium-catalyzed reactions of 1,4-dienes by Larock and coworkers29. Akermark and coworkers have demonstrated the stereochemistry of this process by the transformation of 1,4-cyclohexadiene to the ( r-allyl)palladium complex 26 by treatment... 

In 1971, Brown and Davidson reported that 1,3-cyclohexadiene undergoes a palladium-catalyzed 1,4-diacetoxylation of unspecified stereochemistry28. The oxidant employed was p-benzoquinone. They were uncertain about the mechanism at the time but later work has shown that the reaction proceeds via a (jr-allyl)palladium intermediate and subsequent nucleophilic attack by acetate6,7. 

Allylic amination is important for the solid-phase organic synthesis.15 The solid-phase allylic aminations are devised into the G-N bond formation on solid support and the deprotection of allyl ethers. As a novel deprotection method, the palladium-catalyzed cyclization-cleavage strategy was reported by Brown et al. (Equation (4)).15a,15b The solid-phase synthesis of several pyrrolidines 70 was achieved by using palladium-catalyzed nucleophilic cleavage of allylic linkages of 69. 

Generation and Reaction of Allyltitanium Reagents (Section 9.3) 2-(4-Bromophenyl)-l-phenyl-3-buten-l-ol [42] To a solution of l-(4-bromophenyl)allyl ethyl carbonate (285 mg, 1.0 mmol) and Ti(OiPr)4 (0.296 mL, 1.0 mmol) in diethyl ether (5 mL) was added iPrMgBr (1.20 m in diethyl ether, 2.0 mmol) at 50 °C. The resulting yellow solution was stirred at —50 to —40 °C for 1.5 h, in the course of which it became brown. Benzaldehyde (74.3 mg, 0.70 mmol) was then added at —40 °C and the mixture was allowed to warm to 0 °C over a period of 30 min. After the addition of aqueous 1 n HC1 (5 mL) at this temperature, the mixture was allowed to warm to ambient temperature. The organic layer was separated and the aqueous layer was extracted with diethyl ether (10 mL). The combined organic layers were washed with saturated aqueous NaHC03 solution (5 mL), dried over... 

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