Allyl additions simple diastereoselectivity

The carbonyl addition reactions of benzylmetals, compared to the allylic counterparts, have found few applications in stereoselective synthesis, apparently for the following reasons The carbonyl addition of alkali metal salts (M = Li, Na, K, Cs) of benzyl anions, with few exceptions, usually proceeds with low levels of simple diastereoselectivity affording mixtures of syn- or <7 / -diastereomers (see Section 1.3.2.3.1.). 

The addition of iodine azide to primary allylic alcohols occurred with complete regio- and simple diastereoselectivity allowing the direct preparation of valuable 3-azido-1,2-epoxides, e.g., 12 and 13, by base-promoted elimination of hydrogen iodide from the intermediate 3-azido-2-iodo alcohols44. 

The addition of iodine azide to 3-/ 7-butylcyclohexcnc in either acetonitrile or dichloromethane gave in moderate yields a mixture of, 2-trans-2,3-cis- and 1,2-trans-2f-trans- -azido-2-iodo-3-ferr-butylcyclohexane 1, with complete regio- and simple diastereoselectivity but moderate induced diastereoselectivity45 46. The stereochemical outcome is explained by assuming the reversible formation of asymmetric iodonium ions (cis and tram to f-Bu), and the preferential attack of azide ion on the cis iodonium ion (antiparallel to the axial allylic hydrogen)46. 

Allylic azides, e.g., 1, were produced by treatment of the triisopropylsilyl enol ethers of cyclic ketones with azidotrimethylsilane and iodosobenzene78, but by lowering the temperature and in the presence of the stable radical 2,2,6,6-tetramethylpiperidine-/V-oxyl (TEMPO), 1-triso-propylsilyloxy-l,2-diazides, e.g., 2, became the predominant product79. The radical mechanism of the reaction was demonstrated. A number of 1,2-diazides (Table 4) were produced in the determined optimum conditions (Method B 16h). The simple diastereoselectivity (trans addition) was complete only with the enol ethers of unsubstituted cycloalkanones or 4-tert-butylcy-clohexanone. This 1,2-bis-azidonation procedure has not been exploited to prepare a-azide ketones, which should be available by simple hydrolysis of the adducts. Instead, the cis-l-triiso-propylsilyloxy-1,2-diazides were applied to the preparation of cw-2-azido tertiary cyclohexanols by selective substitution of the C-l azide group by nucleophiles in the presence of Lewis acids. 

In order to explain the chemistry of allylic metals, the reactions of allylic boron compounds [8,12-14] are covered in detail. The boron chemistry is divided into four parts simple enantioselectivity (addition of CH2=CHCH2-, creating one new stereocenter), simple diastereoselectivity of crotyl additions (relative configuration after CH3CH=CHCH2- addition, where neither reagent is chiral), single asymmetric induction with chiral allyl boron compounds (one and two new stereocenters), and double asymmetric induction (both reactants chiral, one and two new stereocenters). Then follows a brief discussion of other allyl metal systems. 

The allylation and crotylation of aldehydes provide attractive alternatives to asymmetric acetate and propionate aldol addition reactions for the construction of /1-hydroxy aldehydes or ketones (Scheme 5.2 see also Chapter 4). In analogy to propionate aldol addition reactions, an important stereochemical feature involving the addition of substituted allylation reagents to aldehydes is simple diastereoselectivity namely, the formation of 1,2-syn versus 1,2-anti products. Although the underlying reasons for absolute and relative induction have yet to be studied in mechanistic detail for many of these processes, there are a collection of methods that reliably and predictably furnish optically active adducts. 

Addition of racemic allylic sulfoxide anions to 2(5//)-furanone gives y-1,4-addition adducts1. The simple and induced diastereoselectivities are completely analogous to that of 2-cyclopen-tenone described earlier. 

The Lewis acid catalyzed conjugate addition of allylsilanes (140) to (142) and allylstannanes (154) and (155) to ot,0-enones, described by Sakurai,68a,68b is highly efficient and experimentally simple in contrast to the allylcuprate additions. Various substituents can be incorporated into the allylsilanes (allylstannanes), e.g. alkoxy, alkoxycarbonyl and halogen, some of which are incompatible with cuprate reagents 69 In addition, Heathcock and Yamamoto report that diastereoselectivity is correlated to the alkene geometry of both the allylmetals and the acceptor units for example, allylation of ( )-enones (143) and (146) affords predominantly the syn adducts (144) and (147), while (Z)-enone (149) gives predominantly the anti adduct (150 Scheme 25).680 On the other hand, with cyclohexen-2-one the (Z)-silane (141) affords predominantly the threo adduct (152), while (142) affords erythro adduct (ISS).686 The more reactive allylstannanes (154) and (155) also afford similar diastereoselectivity.68e,f... 

Diastereoselective alkylation of tartaric acid. The enolate (2) of the acetonide of dimethyl (R, R)-tartrate (1) can be generated with LDA in THF-HMPT at — 70° and is sufficiently stable for alkylation with allyl and benzyl halides, but not with other simple alkyl halides, and for addition to acetone (60% yield). The main products (3) of allylation and benzylation have the /ranr-configuration, and thus the substitution occurs with retention of configuration.7... 

Looking for a suitable preparation of dihydrobenzofuran derivatives by carbolithiation reactions, we have recently described how allyl 2-bromophenyl ethers 358 with a substituent at the a-position afford, after treatment with r-BuLi, addition of TMEDA and further quenching with electrophiles, functionalized fraws-2,3-dihydrobenzofuran derivatives 359 in a totally diastereoselective manner (Scheme 94)155. The key for the success of this reaction is the fact that intermediate organolithium 360 is not prone to undergo the 1,3-elimination process, probably due to the steric effect of the R substituent. The high diastereoselectivity of the ring closure could be explained by a transition state that accommodates the R group in a pseudoequatorial position. Moreover, simple allyl... 

Recently, Shibasaki and co-workers reported a copperreaction using a chiral diphosphine ligand, DuPHOS, with an added lanthanide salt (118]. This new allylation system provides good levels of enantioselectivity in additions of the simple allylboronate 2 to either aromatic or aliphatic ketones that present a large difference of steric bulk on both sides of the carbonyl (Equation 43). Based on NMR experiments and on the lack of diastereoselectivity in crotylation examples, the suggested mechanism of this allylation involves transmetallation of the boron to an allylcopper species. 

Simple stereoinduction in the Diels-Alder reaction typically follows a number of general guidelines. Two of these are well known to the student of organic chemistry, namely the notable preference for endo selectivity, as a consequence of secondary orbital overlap, and regioselectivity consistent with the optimal interactions of the frontier molecular orbitals [38]. Additional stereochemical preferences may also be observed for chiral reacting partners. In a study by Overman with cyclic dienes such as 30, cycloaddition was observed to occur on the olefin face anti to the allylic substituent in 30 (Scheme 17.7) [39]. The superimposition of the basic stereochemical features of the Diels-Alder reaction (i.e., endo selectivity cf 32) on the steric differentiation of the olefin faces leads to the preferential formation of 33-35 with increasing diastereoselectivity as a function of the size of the substituent X. 

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