Lewis acid-promoted addition of allylsilane

The Lewis acid promoted addition of allylsilane (48) to nitroalkoie (47) gave the unsaturated ketone... 

The Lewis acid promoted addition of allylsilane (48) to nitroalkene (47) gave the unsaturated ketone (49) after hydrolysis of the nitro group. The palladium-catalyzed oxidation affords the 1,4-diketone (50 Scheme 13). °... 

N,P ] The Lewis-acid-promoted additions of allylsilanes and meth-allylsilanes to several chiral a,/ -unsaturated ketones (Sakurai reaction) are summarized in Scheme 31 and Table 8 (67).J The most effective catalyst for the... 

Mechanistic Aspects - Lewis Acid-Promoted Addition of Allylsilanes and Allylstannanes to Aldehydes... 

The majority of catalytic enantioselective allylation reactions involve the chiral Lewis-acid-catalysed additions of allylsilanes or allylstannanes to carbonyl compounds. Monothiobinaphthol has been used by Woodward et al. as a chiral promoter in the enantioselective catalytic allylation of aryl ketones with impure Sn(allyl)4, prepared from allyl chloride, air-oxidised magnesium and SnCl4. Therefore, the allylation of arylketones in these conditions was achieved very efficiently, since the corresponding allylic alcohols were formed in... 

The Lewis acid-catalyzed reactions of allylsilanes with simple alkenes and alkynes introduce both allyl and silyl groups into the unsaturated bonds (Equations (53) and (54)).209 210b These allylsilylations are 7-regiospecific with respect to allylsilanes. The /raor-addition of allylsilanes occurs in the reaction with alkynes. There are two possible mechanisms for the Lewis acid-promoted allylsilylations, that is, trimethylsilyl cation- and Lewis acid-mediated pathways. 

The Lewis acid-promoted reactions of acrylates and propiolates with allylsilanes usually afford [2-1-2] adducts as described in the next section [470-473]. The corresponding [3-1-2] adducts are obtained as minor products although there are a few exceptions. The ratio of the two kinds of cycloadduct depends on the reaction temperature [470] - the proportion of [3-1-2] adducts increases with increasing temperature. The product ratio from cycloaddition to alkylidenemalonates and their derivatives is markedly temperature-dependent (Scheme 10.170) [474, 475]. Cyclobutanes are major products at low temperature, and [3-1-2] cycloaddition proceeds predominantly at higher temperature. In addition, the [2-1-2] cycloadducts are smoothly isomerized to the [3-1-2] adducts in the presence of a Lewis acid. This behavior clearly shows that [3-1-2] cycloaddition is thermodynamically favored. 

Chelation control has been invoked to explain the stereoselectivity of the reaction between 2-methoxycyclohexanone and trimethyl(2-propenyl)silane promoted by titanium(IV) chloride59, and has been observed for addition of allylsilanes to a-amidoaldehydes60, although the stereoselectivity is very dependent upon the amount of Lewis acid used and the structure of the substrate, particularly when the Lewis acid can bind to more than one site61. 

Cyclization to a morpholinolactone (59) occurs in the hydrolysis reaction of the di-A-hydroxylethylated compound (60). Compound (59) is rapidly hydrolysed by water to (61) but in file presence of equimolar amounts of amines (RNH2) or ammo acid derivatives (62) forms.56 A novel reaction of cyclic 2-diazo-l,3-dicarbonyl compounds (63) with lactones (64) affords the products (65) in the presence of rhodium acetate, Rh2(OAc)4.57 Lewis acid-promoted intramolecular additions of allylsilanes to lilac tones gave substituted cyclopentanes.58 A proposed transition state guided efforts to improve the stereoselectivity of the reaction. The reaction of a series of /1-lactone derivatives, such as (66)-(68), has been studied and they have been ling cleaved the reaction outcome is both Lewis acid and structure dependent.59... 

Lewis acid-promoted asymmetric conjugate addition of an allylsilane to a series of 8-arylmenthol-derived A -acy I-2.3-di hydro-4-pyri doncs (122) has been reported to lead to 2-allyl-4-piperidones with moderate to high levels of asymmetric induction the highest levels were attained with Ar = 2-naphthyl. The stereochemical course of the reaction was attributed to re-stacking and the method was applied to the asymmetric synthesis of (—)-A-mcthy Icon i i nc.9 5... 

The first addition of allylsilane 1 to activated carbonyl compounds, such as chloral 2 or a-chloroacetone 4, leading to y-d -un saturated alcohols 3 or 5, was reported by Calas et al. [3, 4] in 1974 and Abel and Rowley [5] in 1975. A Lewis acid, such as AlCfi, GaCfi or InCl3 is required to promote this condensation (Scheme 13.1). 

In this synthesis of 1,5-dicaibonyl compounds, 3-butenyl halide is behaving as a madced 3-oxobutyl reagent, and can be used as an equivalent of metiiyl vinyl ketone. These reactirais offer new anellation methods. Also 1,4-addition of the allyl group to enones, followed by oxidatitm. offers a conveiuent synthetic method for 1,5-diketone preparation. Lewis acid promoted Nfichael addition of allylsilane (48) to a,p-unsaturated ketones, followed by the palladium-catalyzed oxidation, affods 1,5-diketones (Scheme 17). 3... 

The intramolecular version of the Lewis-acid-promoted conjugate addition of allylsilanes to a,/ -unsaturated ketones (Hosomi-Sakurai reaction) has... 

Lewis acids catalyse the addition of allylic organostannanes or organosilanes to aldehydes. In contrast to the thermal reactions of allylboranes or allylstannanes, the use of a Lewis acid promotes reaction via an acyclic transition state. With a y-substituted allylsilane, such as crotyltrimethylsilane 156, the E-isomer reacts with excellent selectivity for the syn product (1.149). The corresponding Z-isomer (of 156) also favours the syn product, although with reduced selectivity (64 36). The transition state is thought to involve the ahgnment of the two tt-bonds 180° to one another (1.150). 

The reaction between allyl nucleophiles and aldehydes or ketones in the presence of titanium Lewis acids gives the homoallylic alcohols that are widely applicable in organic synthesis. The first allylation was reported by Hosomi and Sakurai in 1976 [69]. TiCU was utilized as the promoter to facilitate the addition of allylsilane to aldehydes or ketones. This allylation has the advantage of complete S 2-regiospecificity with regard to the allylic system. Later, Hayashi and Kumada established the acyclic stereochemical outcome of this allylation with a few electrophiles in the presence of TiCU, indicating the anti 8 2 mode of the reaction [70] (Scheme 14.15). 

Activation of C=X Bonds. Lewis acid activation of carbonyl compounds by ZnBr promotes the addition of allylsilanes and silyl ketene acetals. Addition to imines has also been reported. In general, other Lewis acids have been found to be more useful, though in some instances ZnBr has proven to be advantageous (eq 12). ... 

Titanium(IV) is a powerful but selective Lewis acid which can promote the coupling of allylsilanes with carbonyl compounds and derivatives In the presence of titanium tetrachlonde, benzalacetone reacts with allyltnmethylsilane by 1,4-addition to give 4-PHENYL-6-HEPTEN-2-ONE. Similarly, the enol silyl ether of cyclopentanone is coupled with f-pentyl chloride using titanium tetrachlonde to give 2-(tert-PENTYL)CYCLOPENTANONE, an example of a-tert-alkylation of ketones. 

The class of 3-silyl-substituted reagents provides, upon addition with aldehydes, allylic silanes that offer many options for further derivatization. Oxidative processes are described in previous sections (see the sections on Preparation of 1,2-Diols and 1,4-Diols). If the appropriate silicon substituents are chosen, formal [3+2] cycloadditions with aldehydes can be promoted under Lewis acid catalysis. For example, the mismatched addition of the Z-3-propyl-3-benzhydryldimethyl allylsilane 183 to an a-benzyloxy aldehyde proceeds with low diastereofacial selectivity in favor of product 184 however, after protection of the secondary alcohol, an efficient [3+2] annulation provides the polysubsubstituted furan 185 in good yield and acceptable stereoselectivity (Scheme 24). ° The latter is brought forward to a tricyclic unit found in the antitumor natural product angelmicin B. 

Several methods promoted by a stoichiometric amount of chiral Lewis acid 38 [51] or chiral Lewis bases 39 [52, 53] and 40 [53] have been developed for enantioselective indium-mediated allylation of aldehydes and ketones by the Loh group. A combination of a chiral trimethylsilyl ether derived from norpseu-doephedrine and allyltrimethylsilane is also convenient for synthesis of enan-tiopure homoallylic alcohols from ketones [54,55]. Asymmetric carbonyl addition by chirally modified allylic metal reagents, to which chiral auxiliaries are covalently bonded, is also an efficient method to obtain enantiomerically enriched homoallylic alcohols and various excellent chiral allylating agents have been developed for example, (lS,2S)-pseudoephedrine- and (lF,2F)-cyclohex-ane-1,2-diamine-derived allylsilanes [56], polymer-supported chiral allylboron reagents [57], and a bisoxazoline-modified chiral allylzinc reagent [58]. An al-lyl transfer reaction from a chiral crotyl donor opened a way to highly enantioselective and a-selective crotylation of aldehydes [59-62]. Enzymatic routes to enantioselective allylation of carbonyl compounds have still not appeared. 

The addition of an allylsilane to an electrophile was first documented in 1948 by Sommer et al. [6]. These workers predicted that the allylsilane would react with an electrophile to generate a silicon-stabilized cationic intermediate. In 1956, Galas and co-workers demonstrated that allylsilanes undergo an allylic shift in the protiodesilylation of a cyclohexenylsilane to afford a methylidenecyclohexane [7], The first report of the reaction of allylsilanes with carbonyl compounds (1974) is also due to Galas [8]. These authors used activated substrates such as perfluoro-acetone and chloroacetone and AIGI3, GaGl3 or InGl3 as Lewis acids to promote... 

The new diphenylalanine-derived oxazolidinone, 15, is particularly effective when used as an auxiliary on radical 29. The auxiliary can be used in a propagation sequence that involves radical addition followed by trapping of the addition radical with allylstannane or allylsilanes, Eq. (21). Excellent yield and diastereoselectivity are observed if the reaction is carried out in the presence of Lewis acids such as magnesium bromide or lanthanide triflates at —78°C. The reaction promoted by magnesium bromide, for example, provides a diastereomer mixture in excess of 100 1 with a yield of 85%. Sc, Yb, Y, La, or Sm triflates provide similar results in reactions usually carried out in ether. 

Interestingly, changing the radical trap from allylstannane to allylsilane increased the enantioselectivity of these allylations from 76% ee to 90% ee (Eq. 6) [10]. The by-product in the allylstannane reactions is tin halide, which is itself a Lewis acid which can promote achiral allylations. In addition, it was observed that a simple change in Lewis acid reversed the sense of stereoinduction. 

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