Phase allylation

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. 

F.3. Two-Phase Allylic Aminations and Heck Reactions using Thermomorphic Dendritic Catalysts... 

The gas-phase allyl anion, [C3Hj], is readily generated from a mixture of propene and NjO in an i.c.r. mass spectrometer, and its reactions with a mixture of NjO and COF 3 have been studied [468]. The principal reaction observed is [468] ... 

After a number of efforts, the conunercial production of vinyl acetate from ethylene and AcOH was initially established as a Uquid phase process represented by the equation shown in Scheme 5. This process was later replaced by a gas phase process using a supported Pd catalyst. The commercial production of allyl acetate from propene and AcOH (Scheme 6) was also established by the gas phase. Allyl alcohol is produced by using this process. The outline of such developments was reviewed by Tsuji. ... 

Asymmetric and enantioselective syntheses on solid support gained attention in the late 1990s with the first solid-phase allylation chemistry reported by Panek and Zhu but remained slow to grow further. Eventually in the beginning of this century, different research groups made successful efforts to transfer the solution-phase asymmetric chemical transformations onto solid supports and their applications in the library synthesis were realized. In the following section, we overview some of these enantioselective reactions developed on solid phase and their role in the synthesis of interesting small molecules. 

Interestingly, it took almost 8 years when the next solid-phase allylation reaction was reported again using a chiral silane. Tan and coworkers reported the asymmetric allylation of an aliphatic polymer-supported aldehyde using a strained aUylsilacycle 24 developed by Leighton and coworkers (Scheme 7.4b). The homoallylic alcohol 25 was obtained in good enantiopurity and yields. 

Scheme 7.6. Synthesis of 5-lactones using enantioselective solid-phase allylation reaction.

Scheme 7.7. Iterative solid-phase allylation for the synthesis of natural product analogues.

Stabilizing resonances also occur in other systems. Some well-known ones are the allyl radical and square cyclobutadiene. It has been shown that in these cases, the ground-state wave function is constructed from the out-of-phase combination of the two components [24,30]. In Section HI, it is shown that this is also a necessary result of Pauli s principle and the permutational symmetry of the polyelectronic wave function When the number of electron pairs exchanged in a two-state system is even, the ground state is the out-of-phase combination [28]. Three electrons may be considered as two electron pairs, one of which is half-populated. When both electron pahs are fully populated, an antiaromatic system arises ("Section HI). 

We begin by considering a three-atom system, the allyl radical. A two anchor loop applies in this case as illush ated in Figure 12 The phase change takes place at the allyl anchor, and the phase-inverting coordinate is the asymmetric stretch C3 mode of the allyl radical. Quantum chemical calculations confiiin this qualitative view [24,56]. In this particular case only one photochemical product is expected. 

The system provides an opportunity to test our method for finding the conical intersection and the stabilized ground-state structures that are formed by the distortion. Recall that we focus on the distinction between spin-paired structures, rather than true minima. A natural choice for anchors are the two C2v stmctures having A2 and B, symmetry shown in Figures 21 and 22 In principle, each set can serve as the anchors. The reaction converting one type-I structirre to another is phase inverting, since it transforms one allyl structure to another (Fig. 12). 

As shown in Figure 27, an in-phase combination of type-V structures leads to another A] symmetry structures (type-VI), which is expected to be stabilized by allyl cation-type resonance. However, calculation shows that the two shuctures are isoenergetic. The electronic wave function preserves its phase when tr ansported through a complete loop around the degeneracy shown in Figure 25, so that no conical intersection (or an even number of conical intersections) should be enclosed in it. This is obviously in contrast with the Jahn-Teller theorem, that predicts splitting into A and states. 

Figure 27. Top One of the allylic type-VI structures, formed by in-phase combination of type-V structures, Bottom The 6ve type-VI structures,...

With higher alkenes, three kinds of products, namely alkenyl acetates, allylic acetates and dioxygenated products are obtained[142]. The reaction of propylene gives two propenyl acetates (119 and 120) and allyl acetate (121) by the nucleophilic substitution and allylic oxidation. The chemoselective formation of allyl acetate takes place by the gas-phase reaction with the supported Pd(II) and Cu(II) catalyst. Allyl acetate (121) is produced commercially by this method[143]. Methallyl acetate (122) and 2-methylene-1,3-diacetoxypropane (123) are obtained in good yields by the gas-phase oxidation of isobutylene with the supported Pd catalyst[144]. 

The protected nucleoside-3-phosphoramidite monomer units such as 671 are used in the solid-phase oligonucleotide synthesis. In the 60mer synthesis, 104 allylic protective groups are removed in almost 100% overall yield by the single Pd-catalyze reaction with formic acid and BuNH2[432], N,(9-protection of uridine derivatives was carried out under pha.se-transfer conditions[433]. 

Reaction Mechanism. High temperature vapor-phase chlorination of propylene [115-07-17 is a free-radical mechanism in which substitution of an allyhc hydrogen is favored over addition of chlorine to the double bond. Abstraction of allyhc hydrogen is especially favored since the allyl radical intermediate is stabilized by resonance between two symmetrical stmctures, both of which lead to allyl chloride. 

From Allyl Ghloride. The hypochlorination of allyl chloride [107-05-1] gives a mixture of the glycerol dichlorohydrins, 2,3-dichloropropanol and 1,3-dichloropropanol about 7 3 ratio. Because of the poor solubiHty of allyl chloride in water, it is essential to minimize the formation of an organic phase in which direct chlorination of the allyl chloride results in the unwanted by-product 1,2,3-trichloropropane. 

Many techniques have been developed to accomplish this, for example, the use of a cooled recirculating system in which the chlorine is dissolved in one part and the allyl chloride is dissolved and suspended in another (61). The streams are brought together in the main reaction zone and thence to a separator to remove water-insoluble products. Another method involves maintaining any organic phase present in the reaction zone in a highly dispersed condition (62). A continuous reactor consists of a recycle system in which make-up water and allyl chloride in a volume ratio of 10—50 1 are added... 

Compound 1, 2,2-diniethyl-4-pentenal, has been prepared by the Claisen rearrangement route described above and by reaction of isobutyraldehyde with allyl chloride in the presence of aqueous sodium hydroxide and a phase-transfer catalyst. Both routes are applicable to the synthesis of a variety of substituted 4-pentenals. 

A mixture of 3.18 g (10 mmoles) of 17 -hydroxy-2-hydroxymethylene-5a-androstan-3-one, 20 ml dry dimethyl formamide and 0.3 g (13 mmoles) of sodium hydride is stirred for 0.5 hr at room temperature under nitrogen. A total of 1.51 g (12.5 mmoles) of redistilled allyl bromide is added and the mixture is stirred for 1 hr on the steam bath. Aqueous potassium hydroxide (2 g in 5 ml of water) is added and stirring is continued for 1 hr on the steam bath. The reaction mixture is diluted with 50 ml of methylene dichloride followed by careful addition of 300 ml of water. The organic phase is separated and the aqueous phase is again extracted with 50 ml of methylene dichloride. The combined extracts are washed with water, dried over sodium sulfate, filtered and chromatographed on 200 g of silica gel. Elution with pentane-ether (4 1) provides 2a-allyl-17j -hydroxy-5a-androstan-3-one 0.85 g (26%) mp 118-119° [aj 14° (CHCI3), after crystallization from ether-hexane. 

Fluonnated allylic ethers are prepared under phase-transfer catalysis (PTC) in the presence of tetrabutylammonium hydrogen sulfate (TBAH) fJ] (equation 2)... 

P-Fluonne or fluonne further removed from the cation center always inductively destabilizes carbocabons [115, 116] No simple p-fluoroalkyl cations have been observed in either the gas phase or solution, and unhke the cases of the other halogens, there is no evidence for formation of alkyl fltioronium ions (5) in solution [117, 118], although (CH3)2F is long-hved m the gas phase [119] The only P-fluonnated cations observed in solution are those that benefit from additional conjugativc stabilization, such as a-trifluoromethylbenzyl cations [112] and per-fluonnated allyl [120], cydopropenium [112], and tropylium [121] ions... 

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