Aldehydes allylic boranes

Allylic boranes such as 9-allyl-9-BBN react with aldehydes and ketones to give allylic carbinols. The reaction begins by Lewis acid-base coordination at the carbonyl oxygen, which both increases the electrophilicity of the carbonyl group and weakens the C-B bond to the allyl group. The dipolar adduct then reacts through a cyclic TS. Bond formation takes place at the 7-carbon of the allyl group and the double bond shifts.36 After the reaction is complete, the carbinol product is liberated from the borinate ester by displacement with ethanolamine. Yields for a series of aldehydes and ketones were usually above 90% for 9-allyl-9-BBN. 

The allylation reaction has been extended to enantiomerically pure allylic boranes and borinates. For example, the 3-methyl-2-butenyl derivative of (Ipc)2BH reacts with aldehydes to give carbinols of greater than 90% e.e. in most cases.39... 

TS, which is usually based on the chair (Zimmerman-Traxler) model. This pattern is particularly prevalent for the allylic borane reagents, where the Lewis acidity of boron promotes a tight cyclic TS, but at the same time limits the possibility of additional chelation. The dominant factors in these cases are the E- or Z-configuration of the allylic reagent and the conformational preferences of the reacting aldehyde (e.g., a Felkin-type preference.)... 

Scheme 3-47. Reaction of aldehydes with chiral allyl boranes 135. Reprinted with permission by Am. Chem. Soc., Ref. 41.

Unlike aldehydes and ketones, allylic boron compounds are not ubiquitous, commercial organic substrates. There are several methods for the preparation of allylic boronates, however, and many of these have been developed in the past decade. This topic has been reviewed recently " so only the most common methods are emphasized in this section. As a result of the lesser stability of allylic boranes, methods to access these reagents are more limited and it is generally easier to prepare allylic boronates with a wide range of functional groups. 

The boron-oxygen mesomeric effect described in the previous section explains the lower reactivity of allylic boronates towards carbonyl compounds compared to that of allylic boranes. The use of Lewis acids, however, allows boronate derivatives, including hindered ones, to react at temperatures comparable to the analogous boranes. As described above (see section Mechanism and Stereochemistry ), the most reactive allylic boronates are those with the most electrophilic boron centers.The nucleophilicity of the y-position of an allylic boron reagent (the position that forms the new C-C bond with the aldehyde) is also important to the reactivity of the reagent. For example, allylic boronates with... 

To improve the levels of selectivity in additions to chiral aldehydes, it is possible to resort to the tactic of double diastereoselection with the use of chiral allylic boranes and boronates (see section Double Diastereoselection ). Bis(isopinocampheyl) allylic boranes and the tartrate allylic boronates (see following section), in particular, are very useful in the synthesis of polypropionate natmal products by reaction with a-methyl and a-alkoxy functionalized aldehydes. 

Scheme 7. Model for absolute stereoinduction in additions of (—)-bis(isopinocampheyl) allylic boranes to aldehydes.

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. 

Although the allylation reaction is formally analogous to the addition of allylboranes to carbonyl derivatives, it does not appear to occur through a cyclic transition state. This is because, in contrast to the boron in allyl boranes, the silicon in allylic silanes has no Lewis acid character and would not be expected to coordinate at the carbonyl oxygen. The stereochemistry of addition of allylic silanes to carbonyl compounds is consistent with an acyclic transition state. Both the E- and Z-stereoisomers of 2-butenyl(trimethyl)silane give the product in which the newly formed hydroxyl group is syn to the methyl substituent.64 The preferred orientation of approach by the silane minimizes interaction between the aldehyde substituent R and the methyl group. 

The following reactions proceed with the participation of the allylic boron system (i) allylboration and protolytic cleavage of organic compounds with multiple bonds, (ii) allylboron-alkyne condensation,598 599 (iii) reductive mono-and trans-a,a -diallylation of nitrogen aromatic compounds, (iv) disproportionation processes between tribut-2-enylborane and BX3 (X = C1, Br, OR, SR). Allylboration of carbonyl compounds, thioketones, imines, or nitriles leads to the homoallylic alcohols, thiols, or amines (Equations (136) and (137). It is most important that 1,2-addition to aldehydes and imines proceeds with high diastereoselectivity so that ( )-allylic boranes and boronates give the anti-products, while -products are formed preferentially from (Z)-isomers. 

Chiral homoallylic alcohols, The glycol 1 has been used as the chiral matrbt in an enantioselective synthesis of homoallylic alcohols (4) from aldehydes and allyl-boranes (equation I). 

There is a vast array of carbon-carbon-bond-forming reactions involving organoboron compounds. This section covers transfer reactions of carbon moieties from boron to an adjacent carbon. Examples include the transfer of CO, CN, carbanions derived from dichloromethyl methyl ether and dichloromethane, and allyl groups in reactions of allylic boranes with aldehydes. 

The use of enantiopure allylic boranes in reactions with achiral aldehydes results not only in high diastereoselection, but also in high enantioselectionP Pure (Z)- and )-crotyldiisopinocampheylboranes can be prepared at low temperature from (Z)- or E) crotylpotassium and S-methoxydiisopinocampheylborane, respectively, after treatment of the resultant ate-complexes with BF3 OEt2. The R-methoxydiisopinocampheylboranes are prepared by reacting (-)-diisopinocampheylborane, derived from (+)-a-pinene, or (+)-diisopinocampheylborane, derived from (-)-a-pinene, with methanol. 

A theoretical study of the effects of structure and substituents on reactivity in allylboration has recently been completed [116]. Electron delocalization from the oxygen of an attacking aldehyde to the boron p-type atomic orbital is crucial in the allylboration reaction. The ab initio molecular orbital study indicates that the complex between the allylic borane and the aldehyde is weak. The relative elec-trophilicity of the boron atom in allylboron reagents is estimated by projecting out the unoccupied reactive orbital having the maximum amplitude onto the boron p-type atomic orbital. Two factors which are considered to be of importance in the reaction include the electron accepting level of the reactive unoccupied orbital and the efficiency of localization of the orbital in the unoccupied MO space. 

Achiral allylic boranes and chiral aldehydes. The reaction of pinacol-derived al-lylboronate 175 with a number of chiral aldehydes proceeds in only modest selectivity (Scheme 10-73) [120], Almost all of the aldehydes examined demonstrate a weak preference for the syn or Cram product. Almost no change in selectivity was observed when the protecting group on the alcohol is changed from a /-butyl-siloxy to a methoxymethyl group. 

Chiral allylic boranes and chiral aldehydes. The possibilities for double diastereo-selection with allylic borane reagents was first demonstrated by Hoffmann in the combination of chiral 2-butenylboronates with chiral aldehydes [123]. Reaction of... 

Simple alkyl boranes do not react with aldehydes and ketones but allyl boranes react rapidly because they can use a six-membered cyclic transition state 68 not unlike that of the Claisen rearrangement. The evidence for this is that the allyl group is rearranged in the product. In this example a crotyl borane 66 adds to an aldehyde to give anti-70 since both R and Me prefer to be equatorial in the transition state 68. 

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