Chiral compounds crotylation

Chiral compounds of this class condense with aldehydes to give a reasonable degree of enantioselective synthesis of homoallylic alcohols. Reaction of (-)-(S)-(neomenthylcyclopentadienyl) Mo(NO)Cl(Ji-syn-crotyl) 47 with benzaldehyde affords (+)-( , /f)-2-methyl-l-phenyl-3-buten-l-ol 48 with >98% ee. (+) and (-) chiral... 

Reaction of 2-[A -(rra -crotyl)-A -benzylamino]-3-formyl-4/f-pyrido[l,2-n]pyrimidin-4-one (269) with chiral primary amines 270 and 271 gave mixtures of diastereoisomers of tetracyclic compounds 273 and tricyclic 275 (96T131]]). The chiral centers in 272 and 274 did not provide any stereocontrol for the formation of diastereomers 273 and 275, respectively. 

Several methods promoted by a stoichiometric amount of chiral Lewis acid 38 [51] or chiral Lewis bases 39 [52, 53] and 40 [53] have been developed for enantioselective indium-mediated allylation of aldehydes and ketones by the Loh group. A combination of a chiral trimethylsilyl ether derived from norpseu-doephedrine and allyltrimethylsilane is also convenient for synthesis of enan-tiopure homoallylic alcohols from ketones [54,55]. Asymmetric carbonyl addition by chirally modified allylic metal reagents, to which chiral auxiliaries are covalently bonded, is also an efficient method to obtain enantiomerically enriched homoallylic alcohols and various excellent chiral allylating agents have been developed for example, (lS,2S)-pseudoephedrine- and (lF,2F)-cyclohex-ane-1,2-diamine-derived allylsilanes [56], polymer-supported chiral allylboron reagents [57], and a bisoxazoline-modified chiral allylzinc reagent [58]. An al-lyl transfer reaction from a chiral crotyl donor opened a way to highly enantioselective and a-selective crotylation of aldehydes [59-62]. Enzymatic routes to enantioselective allylation of carbonyl compounds have still not appeared. 

Solid-supported synthesis has rapidly emerged as an important strategy in synthetic organic chemistry. Solid-phase methodology is aimed at the direct synthesis of libraries of molecularly diverse compounds for biological evaluation in lead discovery. The asymmetric addition of polymer-supported chiral crotylsilanes to acetals and allylation of polymer-bound acetals linked through an ester with the chiral crotylsilanes has been investigated [44d] la can be employed in these crotylation reactions and results in the formation of polymer-supported homoallylic esters with diastereoselec-tivity similar to that of solution-phase reactions. 

The two stereogenic centers of the target compound were concomitantly introduced by a diastereo- and enantio selective crotylation technique employing a chiral crotyl silane. The syn/anti selectivity of this reaction was improved dramatically by converting the propargylic starting material into the corresponding hexacarbonyldicobalt complex. 

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. 

Noteworthy among these examples is the ability to achieve high diastereoselec-tivity for both the 3,4-syn and 3,4-anti isomers, almost independent of the chirality sense of the aldehyde. Comparison of several examples show the expected trends for matched and mismatched pairs (c/. entry pairs 1/2, 4/6, 5/7, 9/12, 16/17). Note that either 3,4-anti diastereomer can be obtained with 96% ds (entries 8 and 12) the two 3,4-syn isomers are also available selectively (entries 13-16 and 17), although only one ligand (5.1i) is selective for the 3,4-syn-4,5-syn product (entry 17) that is a mismatched pair cf. entry 16). Note that with Roush s tartrate ligand (Figure 5.1c), the -crotyl mismatched pair is more selective than the matched pair (entries 8/11 for a rationale, see ref. [33]), and the matched and mismatched pair give the same major product isomer with the Z-crotyl compound (entries 14/15). 

Patterson and co-workers113 observed that the thermal rearrangement of N-alkylpyrroles led to a mixture of 2- and 3-alkyl derivatives and suggested that a 2JF/-pyrrole was an intermediate. Photolysis of the same class of compounds, using a low-pressure Hg lamp, led to isolable 2/f-pyrroles as well as 3-alkylpyrroles (Scheme 42).19,20 A chiral group migrates with some retention of optical activity,19 and an /V-(a-methallyl) derivative gave a mixture of a-methallyl and cis- and trans-crotyl products.20 The 3-isomer appears to arise from a direct [l,3]-shift rather than via the 2f/-pyrrole.20... 

The enantioselective lithiation of anisolechroimum tricarbonyl was used by Schmalz in a route towards the natural product (+)-ptilocaulin [88,89]. In situ hthiation of 125 with ent-83 gave enf-126 in an optimised 91% ee (reaction carried out at -100°C over 10 min). A second, substrate-directed lithiation with BuLi alone, formation of the copper derivative, and a quench with crotyl bromide, gave 135. The planar chirality and reactivity of the chromium complex was then exploited in a nucleophilic addition of dithiane, which generated the ptilocaulin precursor 136 (Scheme 35). The stereochemistry of compound 126 has also been used to direct dearomatising additions, yielding other classes of enones [90]. 

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