Boron, stereochemistry

What happens to the boron stereochemistry and the molecular stability when attempts are made to remove the ammonia by reacting the diadduct with a stronger Lewis acid ... 

The specific recognition of cis-diol function by the boronic acid derivatives was the subject of many researches. In fact, certain authors used this affinity for controlling the reversible immobilization of proteins, enzymes, or all biomolecules bearing glucose site. This interadion is sensitive to the pH of the medium due to the pAf of the boronic acid involved in such affinity. This is due to the effect of the pH on the boronic stereochemistry of the acid. Indeed, it is trigonal in form at low pH and tetragonal at basic pH (i.e., pH > = 8.8). Thus, the complexation reaction is favored at basic... 

CHR) , formed, e g. from the reaction of diazomethane and alcohols or hydroxylamine derivatives in the presence of boron compounds or with metal compounds. Poly-methylene is formally the same as polyethene and the properties of the various polymers depend upon the degree of polymerization and the stereochemistry. 

Stereoselectivities of 99% are also obtained by Mukaiyama type aldol reactions (cf. p. 58) of the titanium enolate of Masamune s chired a-silyloxy ketone with aldehydes. An excess of titanium reagent (s 2 mol) must be used to prevent interference by the lithium salt formed, when the titanium enolate is generated via the lithium enolate (C. Siegel, 1989). The mechanism and the stereochemistry are the same as with the boron enolate. 

The chemistry and stereochemistry of aminoboranes containing the siLicon—nitrogen—boron linkage have been the subject of numerous studies. Many of these compounds are useful precursors to other B—N systems including diboryl-amines (45) and B—H substituted aminoboranes (46). A series of... 

The boron trifluoride-ether complex has been employed mainly in the opening of 5,6-epoxides. This reaction was first studied by Henbest and Wrigley and affords products depending on the nature and stereochemistry of the... 

There appears to be no end to the structural ingenuity of boron and, whilst it is true that many regularities can now be discerned in its stereochemistry, much more work is still needed to unravel the reaction pathways by which the compounds are formed and to elucidate the mechanisms by which they isomerize and interconvert. 

One interesting phenomenon was the effect of the boron substituent on enantioselectivity. The stereochemistry of the reaction of a-substituted a,/ -unsatu-rated aldehydes was completely independent of the steric features of the boron substituents, probably because of a preference for the s-trans conformation in the transition state in all cases. On the other hand, the stereochemistry of the reaction of cyclopentadiene with a-unsubstituted a,/ -unsaturated aldehydes was dramatically reversed on altering the structure of the boron substituents, because the stable conformation changed from s-cis to s-trans, resulting in production of the opposite enantiomer. It should be noted that selective cycloadditions of a-unsubsti-tuted a,/ -unsaturated aldehydes are rarer than those of a-substituted a,/ -unsatu-... 

One of the features that makes the hydrobora ( ion reaction so useful is the regiochemistry that results when an unsymmetrical alkene is hydroborated. For example, hydroboration/oxidation of 1-methylcyclopentene yields trans-2-methylcydopentanol. Boron and hydrogen both add to the alkene from the same face of the double bond—that is, with syn stereochemistry, the opposite of anti—with boron attaching to the less highly substituted carbon. During the oxidation step, the boron is replaced by an -OH with the same stereochemistry, resulting in an overall syn non-Markovnikov addition of water. This stereochemical result is particularly useful because it is complementary to the Markovnikov regiochemistry observed for oxymercuration. 

Scheme 5 details the asymmetric synthesis of dimethylhydrazone 14. The synthesis of this fragment commences with an Evans asymmetric aldol condensation between the boron enolate derived from 21 and trans-2-pentenal (20). Syn aldol adduct 29 is obtained in diastereomerically pure form through a process which defines both the relative and absolute stereochemistry of the newly generated stereogenic centers at carbons 29 and 30 (92 % yield). After reductive removal of the chiral auxiliary, selective silylation of the primary alcohol furnishes 30 in 71 % overall yield. The method employed to achieve the reduction of the C-28 carbonyl is interesting and worthy of comment. The reaction between tri-n-butylbor-... 

The syn selectivity in the titanium(IV) chloride mediated reactions can be explained by an intermolecular chelation, with transition state 21A being sterically favored over 21B. On the other hand, nonchelation control governs the stereochemistry of the boron trifluoride mediated reactions. Thus, the sterically favored transition state 21 C leads to the observed anf/ -diastereo-mer12. 

Note also the stereochemistry. In some cases, two new stereogenic centers are formed. The hydroxyl group and any C(2) substituent on the enolate can be in a syn or anti relationship. For many aldol addition reactions, the stereochemical outcome of the reaction can be predicted and analyzed on the basis of the detailed mechanism of the reaction. Entry 1 is a mixed ketone-aldehyde aldol addition carried out by kinetic formation of the less-substituted ketone enolate. Entries 2 to 4 are similar reactions but with more highly substituted reactants. Entries 5 and 6 involve boron enolates, which are discussed in Section 2.1.2.2. Entry 7 shows the formation of a boron enolate of an amide reactions of this type are considered in Section 2.1.3. Entries 8 to 10 show titanium, tin, and zirconium enolates and are discussed in Section 2.1.2.3. 

Aldol Reactions of Boron Enolates. The matter of increasing stereoselectivity in the addition step can be addressed by using other reactants. One important version of the aldol reaction involves the use of boron enolates.15 A cyclic TS similar to that for lithium enolates is involved, and the same relationship exists between enolate configuration and product stereochemistry. In general, the stereoselectivity is higher than for lithium enolates. The O-B bond distances are shorter than for lithium enolates, and this leads to a more compact structure for the TS and magnifies the steric interactions that control stereoselectivity. 

The general trend is that boron enolates parallel lithium enolates in their stereoselectivity but show enhanced stereoselectivity. There also are some advantages in terms of access to both stereoisomeric enol derivatives. Another important characteristic of boron enolates is that they are not subject to internal chelation. The tetracoordinate dialkylboron in the cyclic TS is not able to accept additional ligands, so there is no tendency to form a chelated TS when the aldehyde or enolate carries a donor substituent. Table 2.2 gives some typical data for boron enolates and shows the strong correspondence between enolate configuration and product stereochemistry. 

A 3 -benzyloxy ketone gives preferential 2,2 -syn stereochemistry through a chelated TS for several titanium enolates. The best results were obtained using isopropoxytitanium trichloride.112 The corresponding /(-boron enolate gives the 2,2 -anti-2,3-anti isomer as the main product through a nonchelated TS.110... 

Scheme 2.6 shows some examples of the use of chiral auxiliaries in the aldol and Mukaiyama reactions. The reaction in Entry 1 involves an achiral aldehyde and the chiral auxiliary is the only influence on the reaction diastereoselectivity, which is very high. The Z-boron enolate results in syn diastereoselectivity. Entry 2 has both an a-methyl and a (3-benzyloxy substituent in the aldehyde reactant. The 2,3-syn relationship arises from the Z-configuration of the enolate, and the 3,4-anti stereochemistry is determined by the stereocenters in the aldehyde. The product was isolated as an ester after methanolysis. Entry 3, which is very similar to Entry 2, was done on a 60-kg scale in a process development investigation for the potential antitumor agent (+)-discodermolide (see page 1244). 

Stereochemical Control Through Reaction Conditions. In the early 1990s it was found that the stereochemistry of reactions of boron enolates of N-acyloxazolidinones can be altered by using a Lewis acid complex of the aldehyde or an excess of the Lewis acid. These reactions are considered to take place through an open TS, with the stereoselectivity dependent on the steric demands of the Lewis acid. With various aldehydes, TiCl4 gave a syn isomer, whereas the reaction was... 

The cyclic mechanism predicts that the addition reaction will be stereospecific with respect to the geometry of the double bond in the allylic group, and this has been demonstrated to be the case. The E- and Z-2-butenyl cyclic boronates 1 and 2 were synthesized and allowed to react with aldehydes. The F-boronate gave the carbinol with anti stereochemistry, whereas the Z-boronate resulted in the syn product.37... 

Carbocation intermediates are involved and the structure and stereochemistry of the product are determined by the factors that govern substituent migration in the carbocation. Clean, high-yield reactions can be expected only where structural or conformational factors promote a selective rearrangement. Boron trifluoride is frequently used... 

The synthesis in Scheme 13.49 features use of an enantioselective allylic boronate reagent derived from diisopropyl tartrate to establish the C(4) and C(5) stereochemistry. The ring is closed by an olefin metathesis reaction. The C(2) methyl group was introduced by alkylation of the lactone enolate. The alkylation is not stereoselective, but base-catalyzed epimerization favors the desired stereoisomer by 4 1. 

Scheme 13.71 shows the most recent version of a synthesis of (-l-)-discodermolide developed by Ian Paterson s group at Cambridge University. The synthesis was based on three major subunits and used boron enolate aldol addition reactions to establish the stereochemistry. 

Derivatives 80 and 81 have the same stereochemistry, indicating the deviation of the boron from trigonal-planar geometry into a pyramidal one (Table 5). 

Structurally novel /3-lactams were obtained using enantiopure 4-oxoazetidine-2-carbaldehydes and methylene cyclohexane and a-methyl styrene (Equation (4)).7 Boron trifluoride diethyletherate and tin(iv) chloride produced the products in the highest yields, and all ene products possessed yy/z-stereochemistry. 

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