Multigram scale

The resolving of a variety of a-substituted carboxyHc acid esters by a previously undescribed enzyme, Candida lipolytica esterase, has been reported (64). a-Methyl-a-amino (49) and a-methyl-a-hydrazino (48) esters, which function as inhibitors of acid decarboxylase enzymes, are obtained on a multigram scale in optically pure form. 

Evans and Colombo35 are developing a different route to enantiomerically pure sulfoxides involving intermediate N-sulfinyl oxazolidinones 5. Reaction of these dia-stereomerically pure species with organometallic reagents gives enantiomerically pure sulfoxides, as illustrated by equation 5 carried out on a multigram scale. 

The iodoalanine derivative is available in both enantiomeric forms and this method offers an extremely simple route to large numbers of non-natural amino acids.4 Therefore a reliable and practical method for the synthesis of fully protected iodoalanine 3 in a multigram scale is highly desirable. 

The data presented in Figure 8 graphically illustrate the tremendous and rapid growth in interest in FOSS chemistry, especially for patented applications. This looks set to continue with current applications in areas as diverse as dendrimers, composite materials, polymers, optical materials, liquid crystal materials, atom scavengers, and cosmetics, and, no doubt, many new areas to come. These many applications derive from the symmetrical nature of the FOSS cores which comprise relatively rigid, near-tetrahedral vertices connected by more flexible siloxane bonds. The compounds are usually thermally and chemically stable and can be modified by conventional synthetic methods and are amenable to the usual characterization techniques. The recent commercial availability of a wide range of simple monomers on a multigram scale will help to advance research in the area more rapidly. 

It should also be mentioned that chemoenzymatic epoxidation reactions have been proposed using lipase and H2O2 on multigram scale [120]. 

Via these optimized routes, the N-protected pyrimidine nucleoamino acids 6 and 9 were synthesized very efficiently in three high-yielding steps, starting from an inexpensive and commercially available serine derivative. The common intermediate O-MTM ether 3 can be synthesized on a multigram scale and is stable for years if stored in a refrigerator. 

Lassaletta et al. designed new hgands for the copper-catalyzed Diels-Alder reaction by introduction of C2-symmetric dialkylamino substructures in gly-oxal bis-hydrazones [104] (73 in Scheme 40). This hgand can advantageously be prepared in its both enantiomeric forms on a multigram scale from 1,4-diphenylbutanedione. 

The homoallylation is applicable to multigram-scale experiments (Scheme 15) [36]. In the presence of 3mol% of Ni(acac)2, a mixture of 25 mmol of benzaldehyde, 50 mmol of Et3B, and 50 mmol of isoprene provides anti-3-methyl-l-phenyl-4-pentenol in 92% yield (4.1 g) with excellent 1,3-anti stereoselectivity. The product is purified by means of a single Kugelrohr distillation of the reaction mixture after an appropriate aqueous workup. 

Scheme 15 Multigram-scale experiments Et3B-Ni catalysis for aromatic aldehydes and Et2Zn-Ni catalysis for aliphatic aldehydes and their variation (Eq. 15)...

Toma and coworkers have described the solvent-free synthesis of salicylanilides from phenyl salicylate or phenyl 4-methoxysalicylate and substituted anilines (Scheme 6.155) [302]. By exposing an equimolar mixture of the ester and the amine to microwave irradiation at 150-220 °C for 4—8 min under open-vessel conditions, good yields of the corresponding salicylanilides were obtained. This synthesis was carried out on a multigram scale (0.1 mol). 

Very recently the tandem hydroformylation/acetalization has been used for the synthesis of new synthetically valuable chiral auxiliary derived from camphor. Stereoselective allylation of camphor and subsequent terminal hydroformylation of the resulting homoallylic alcohol affords the 5-lactol auxiliary (camTHP OH) in multigram scale (Scheme 8) [41]. 

Third, some of the pheromone components are simple and cheap compounds such as straight-chain esters and aldehydes, that are readily available in bulk. Others fall into a middle ground, whereby multigram-scale synthesis to produce sufficient material for use as trap lures should be possible. However, the pheromone structures of a number of species appear to be of sufficient complexity that it is unlikely that they could be made in sufficient quantity and at affordable cost for widespread use in pheromone-based control programs. 

Although it was also Henbest who reported as early as 1965 the first asymmetric epoxidation by using a chiral peracid, without doubt, one of the methods of enantioselective synthesis most frequently used in the past few years has been the "asymmetric epoxidation" reported in 1980 by K.B. Sharpless [3] which meets almost all the requirements for being an "ideal" reaction. That is to say, complete stereofacial selectivities are achieved under catalytic conditions and working at the multigram scale. The method, which is summarised in Fig. 10.1, involves the titanium (IV)-catalysed epoxidation of allylic alcohols in the presence of tartaric esters as chiral ligands. The reagents for this asyimnetric epoxidation of primary allylic alcohols are L-(+)- or D-(-)-diethyl (DET) or diisopropyl (DIPT) tartrate,27 titanium tetraisopropoxide and water free solutions of fert-butyl hydroperoxide. The natural and unnatural diethyl tartrates, as well as titanium tetraisopropoxide are commercially available, and the required water-free solution of tert-bnty hydroperoxide is easily prepared from the commercially available isooctane solutions. 

The almond meal PaHnl can be obtained from commercial sources or alternatively can be prepared [42,43] by grinding almonds and defatting the powder three times with ethyl acetate. These procedures makes this Hnl an attractive enzyme to use on a multigram scale and hence it has been widely applied in organic synthesis (as outlined in Sect. 3.3.1). 

Example 1 the phosphoroamidite coupling procedure leading to dinucleosides and employing a catalytic amount of 5-(p-nitrophenyl)-lff-tetrazole (NPT) is illustrated [12b]. Dinucleoside phosphates can be prepared by this procedure at a multigram scale in 92-98% yield. The catalyst NPT (5 mol%) is used in the presence of molecular sieves 13X in acetonitrile at 40 °C (step a). 

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