Nucleophilic addition 2-amino alcohol

Only a few examples have been obtained through the classical methodologies followed in group 6 metal chemistry. Most rf -Cs Fischer-type ruthenium and osmium carbenes arise from the nucleophilic additions of alcohol and amino groups at the electrophilic carbenic Ca-atom of both allenylidene and vinylidene complexes. The fate of the reaction depends on the electrophilicity as well as the steric hindrance around the Ca-atom, which can control its accessibility, especially for bulky nucleophiles. These features have been thoroughly discussed in a recent review. ... 

In addition to alcohols, some other nucleophiles such as amines and carbon nucleophiles can be used to trap the acylpalladium intermediates. The o-viny-lidene-/j-lactam 30 is prepared by the carbonylation of the 4-benzylamino-2-alkynyl methyl carbonate derivative 29[16]. The reaction proceeds using TMPP, a cyclic phosphite, as a ligand. When the amino group is protected as the p-toluenesulfonamide, the reaction proceeds in the presence of potassium carbonate, and the f>-alkynyl-/J-lactam 31 is obtained by the isomerization of the allenyl (vinylidene) group to the less strained alkyne. 

Quite a number of asymmetric thiol conjugate addition reactions are known [84], but previous examples of enantioselective thiol conjugate additions were based on the activation of thiol nucleophiles by use of chiral base catalysts such as amino alcohols [85], the lithium thiolate complex of amino bisether [86], and a lanthanide tris(binaphthoxide) [87]. No examples have been reported for the enantioselective thiol conjugate additions through the activation of acceptors by the aid of chiral Lewis acid catalysts. We therefore focussed on the potential of J ,J -DBFOX/ Ph aqua complex catalysts as highly tolerant chiral Lewis acid catalyst in thiol conjugate addition reactions. 

Substitution of an additional nitrogen atom onto the three-carbon side chain also serves to suppress tranquilizing activity at the expense of antispasmodic activity. Reaction of phenothia zine with epichlorohydrin by means of sodium hydride gives the epoxide 121. It should be noted that, even if initial attack in this reaction is on the epoxide, the alkoxide ion that would result from this nucleophilic addition can readily displace the adjacent chlorine to give the observed product. Opening of the oxirane with dimethylamine proceeds at the terminal position to afford the amino alcohol, 122. The amino alcohol is then converted to the halide (123). A displacement reaction with dimethylamine gives aminopromazine (124). ... 

Additions of oxygen and nitrogen nucleophiles to vinyloxiranes can be achieved with Pd(0) catalysis [103, 104]. Acetate, silanols, amines, sulfonamides, and azide have been used as nucleophiles, and the stereochemical outcome of these additions, where applicable, is normally the result of two consecutive SN2 reactions. This is demonstrated by the additions of NaNHTs to vinylepoxides 29 and 30, affording syn- and anti-amino alcohols 31 and 32, respectively, in good yields and with high diastereoselectivities (Scheme 9.22) [105]. 

Photodriven reactions of Fischer carbenes with alcohols produces esters, the expected product from nucleophilic addition to ketenes. Hydroxycarbene complexes, generated in situ by protonation of the corresponding ate complex, produced a-hydroxyesters in modest yield (Table 15) [103]. Ketals,presumably formed by thermal decomposition of the carbenes, were major by-products. The discovery that amides were readily converted to aminocarbene complexes [104] resulted in an efficient approach to a-amino acids by photodriven reaction of these aminocarbenes with alcohols (Table 16) [105,106]. a-Alkylation of the (methyl)(dibenzylamino)carbene complex followed by photolysis produced a range of racemic alanine derivatives (Eq. 26). With chiral oxazolidine carbene complexes optically active amino acid derivatives were available (Eq. 27). Since both enantiomers of the optically active chromium aminocarbene are equally available, both the natural S and unnatural R amino acid derivatives are equally... 

Taking Tomioka s pioneering work [8] as a precedent, we have screened 13-amino alcohols as chiral modifiers [9] in the nucleophilic addition of lithium 2-pyridinylacetylide 6 to the pMB protected ketimine 5. We were pleased to discover that when 5 was treated with a mixture prepared from 1.07 equiv each of quinine and 2-ethynylpyridine by addition of 2.13 equiv of n-BuLi in THF at -40 to -20 °C, the desired adduct 19 was obtained in 84% yield with maximum 64% ee. Soon after, we found selection of the nitrogen protective group had great influence on the outcome of the asymmetric addition and the ANM (9-anthranylmethyl)... 

A typical second step after the insertion of CO into aryl or alkenyl-Pd(II) compounds is the addition to alkenes [148]. However, allenes can also be used (as shown in the following examples) where a it-allyl-r 3-Pd-complex is formed as an intermediate which undergoes a nucleophilic substitution. Thus, Alper and coworkers [148], as well as Grigg and coworkers [149], described a Pd-catalyzed transformation of o-iodophenols and o-iodoanilines with allenes in the presence of CO. Reaction of 6/1-310 or 6/1-311 with 6/1-312 in the presence of Pd° under a CO atmosphere (1 atm) led to the chromanones 6/1-314 and quinolones 6/1-315, respectively, via the Jt-allyl-r 3-Pd-complex 6/1-313 (Scheme 6/1.82). The enones obtained can be transformed by a Michael addition with amines, followed by reduction to give y-amino alcohols. Quinolones and chromanones are of interest due to their pronounced biological activity as antibacterials [150], antifungals [151] and neurotrophic factors [152]. 

One of the most well used methods for the synthesis of aziridines involves a two (or sometimes more) step process in which an epoxide is opened by a nitrogen nucleophile. The resulting P-amino alcohol (e.g. 79) is then converted to an aziridine via a number of different processes. This method is generally not broadly applicable when a variety of different groups on the nitrogen of the aziridine are desired. A useful method to convert an epoxide to a number of different /V-sulfonyl aziridines (e.g. 80) has been reported <06S425>. Simple addition of a sulfonamide to an epoxide provides high yields of 79 which is readily closed to form the aziridine. 

Nucleophilic addition of metal alkyls to carbonyl compounds in the presence of a chiral catalyst has been one of the most extensively explored reactions in asymmetric synthesis. Various chiral amino alcohols as well as diamines with C2 symmetry have been developed as excellent chiral ligands in the enantiose-lective catalytic alkylation of aldehydes with organozincs. Although dialkylzinc compounds are inert to ordinary carbonyl substrates, certain additives can be used to enhance their reactivity. Particularly noteworthy is the finding by Oguni and Omi103 that a small amount of (S)-leucinol catalyzes the reaction of diethylzinc to form (R)-l-phenyl-1 -propanol in 49% ee. This is a case where the... 

The nucleophilic addition of nitroalkane to carbonyl groups is known as the Henry reaction. The products of the Henry reaction are 2-nitroalkanols,115 which are useful intermediates for nitroalkenes, 2-amino alcohols, and 2-nitro-ketones. However, this does not always give high yields because of the possible O-alkylation in preference to C-alkylation during the Henry reaction. 

Cdrdova has shown that using unprotected iV-hydroxycarbamates 71 as the nucleophile with diarylprohnol ether 30 as catalyst gave direct access to 5-hydrox-yisoxazolidines 72 (91-99% ee) which are convenient precursors to p-amino alcohols and p-amino acids (Scheme 31) [110], Interestingly, these reactions proceed efficiently (3-16 h) without the need for an additional co-acid unlike the majority of other iminium ion catalysed transformations, an unexpected result which highlights the need for further mechanistic understanding. 

It has recently been shown that when the tetrahedral intermediate of the reaction is cyclic, it is a better donor of nucleophilic CF3. These cyclic intermediates can be generated intramolecularly from trifluoroacetamides or trifluorosulfmamides derived from (9-silylated ephedrine. These reagents are able to trifluoromethylate aldehydes and ketones, even in the case of enolizable substrates, as a strong base is not required (Figure 2.34). However, while the source of CF3 is chiral, there is no chirality transfer to the addition product, and the replacement of ephedrine by other chiral amino alcohols did not show any improvement. " Similar to asymmetric trifluoromethylation with the Ruppert reagent, only the use of a fluoride salt of cinchonine can increase the enantioselectivity. " " ... 

The addition of nucleophiles to the carbonyl group may be catalysed by acids obtained by the protonation of the carbonyl oxygen (equilibrium 26). Acid catalysis can also occur during the elimination step which follows the addition step. For example, the reactions of aldehydes with amines (and of all the ammonia derivatives) to form imines are generally assumed to occur in two steps the first is the addition of nucleophile to yield a gem amino alcohol, the second includes the elimination of water from the tetrahedral adduct 138 (see Scheme 45). This elimination is usually thought to be catalysed by electrophiles171,212. 

Nucleophilic additions to chiral a-alkoxy and a-amino nitrones have been reviewed, focusing on tuning of Lewis acid catalysts and protecting groups so as to exert stereocontrol in producing hydroxylamines and ultimately useful amino acids, amino alcohols, and nucleoside analogues.96... 

---