Double inversion sequence

In a synthetic application of this double inversion sequence, tris(benzyloxy)bromo boronic ester 6 obtained in the ribose sequence (Section 1.1.2.1.3.2.) is converted to the 4-methoxyphenyl-methoxy derivative 7 in the usual way. 2,3-Dichloro-5,6-dicyano-l,4-benzoquinone cleaves the protecting group to furnish the a-hydroxy boronic ester 8. Conversion of the a-hydroxy boronic ester 8 to the methanesulfonate 9 followed by displacement of the sulfonate by phenylmethoxide yields a-benzyloxy boronic ester 10, which is a diastereomer of one of the ribose intermediates37. 

The double inversion sequence provides unequivocal evidence that the nucleophilic displacements assisted by neighboring boron proceed with inversion of configuration at carbon. 

An improved method for the conversion of lycorine to hippamine (5) has been developed that commenced with the conversion of 2 to the chloride 175 by the action of phosphorus oxychloride and hydrochloric acid (Scheme 18) (729). The retention of configuration at C-2 was presumably the result of a double inversion sequence involving the participation of the acetate group at C-l. Brief treatment of 175 with sodium methoxide in methanol at 0°C proceeded readily to provide lycorene a-oxide (176), which furnished hippamine (5) when heated with so-... 

Methyl penta-A,0-acetyl-a-D-lincosaminide, related to lincomycin (55, X=OH), has been prepared from myo-inosotol/ Lincomycin has been converted by a double inversion sequence via the chloride (clindamycin) into the analogues 55, X=N3, imidazol-2-thiyl, etc/ and the lincosamine-related structure 56 has been made from l,2 3,4-diO-isopropylidene-D-galactose/ ... 

The reactions between metal nucleophiles and organic compounds finds several applications in the areas of organic synthesis and catalysis. One obvious area of application is the control of stereochemistry at the carbon centre when the metal nucleophile inverts the configuration of the carbon in an Sn2 process. In this way the C-20 centre of steroids has been controlled by a double inversion sequence using [Pd(PPh3)3] (Trost and Verhoeven, 1976). Clearly, the choice of nucleophile is important when stereochemically indiscriminate electron-transfer processes are so often energetically very comparable. 

A paper on the use of 1,6-anhydro-hexoses for oligosaccharide synthesis includes a conversion of 1,6-anhydro-2,3-di-0-benzyl-(5-D-glucofuranose to the corresponding 5-azido-5-deoxy analogue (17) by a double inversion sequence, and hence to 1-deoxy-nojirimycin (18)/... 

But what if we wanted to convert (/ )-2-bromooctane into the R thiol One technique uses a sequence of two Sn2 reactions, each resulting in inversion of configuration at the stereocenter. For example, an Sn2 reaction with iodide would first generate (S)-2-iodooctane. We would then use this haloalkane with an inverted configuration as the substrate in a second displacement, now with HS ion, to furnish the R thiol. This double inversion sequence of two Sn2 processes gives us the result we desire, a net retention of configuration. 

Fig. 2 (a) DRAMA pulse sequence (using % = t/2 = rr/4 in the text) and a representative calculated dipolar recoupled frequency domain spectrum (reproduced from [23] with permission), (b) RFDR pulse sequence inserted as mixing block in a 2D 13C-13C chemical shift correlation experiment, along with an experimental spectrum of 13C-labeled alanine (reproduced from [24] with permission), (c) Rotational resonance inversion sequence along with an n = 3 rotational resonance differential dephasing curve for 13C-labeled alanine (reproduced from [21] with permission), (d) Double-quantum HORROR experiment along with a 2D HORROR nutation spectrum of 13C2-2,3-L-alanine (reproduced from [26] with permission)... 

In this reaction sequence, allylic alcohol 6 is converted into 7 with a double inversion of configuration, and thus retention. 

To obtain 6-epi-LTA4 methyl ester (6-epi-LTA4 Me ester) it was necessary to retain the original stereochemistry at C-3 and C-4 of 2-deoxy-D-ribose. Operationally, this was carried out by effecting a double inversion at one center, as illustrated in Sequence 3, on compounds 44 and 49. In contrast, to obtain... 

Double pulse sequences (inversion and saturation recovery)... 

Before we go on, iook back at the first reaction of this sequence—the conversion of L-leuclne to the hydroxy acid. The stereochemistry may surprise you look carefully and you will see that the amino group has been displaced with retention of stereochemistry. Retentive substitutions usually indicate double inversions, and here the carboxylic acid gets involved in the displacement to give (with inversion) a very unstable compound called an a-lactone whose strained ring is opened by water, also with inversion. 

Synthetic efforts towards isochrysohermidin (1) commenced with exploration of the critical double inverse-electron-demand Diels- Alder union of 1,1,4,4-tetramethoxy-1,3-butadiene (28) with tetrazine 8, as shown in Scheme 6." After considerable experimentation, it was found that the desired sequence based on a double [4+2] cycloaddition reaction to produce the 1,2-diazine dimer 27 could be effected in 65 % yield upon treatment of 28 with... 

The reaction shown in Eq. 12.67 gives complete inversion at the stereogenic center attached to Fe. This requires a backside attack, and the most logical way for this to occur is to start with an oxidative addition of the Br2, and then nucleophilic attack by bromide with Fe as the leaving group. The sequence of electrophilic addition of X2 to the metal followed by nucleophilic attack on the ligand is common for middle-to-late transition metals. Interestingly, when phenyl is in the 3-position, the reaction proceeds with retention. Retention is best explained by a double inversion, and the phenonium ion has been substantiated as the intermediate formed (Eq. 12.68). 

The SELINCOR experiment is a selective ID inverse heteronuclear shift-correlation experiment i.e., ID H,C-COSYinverse experiment) (Berger, 1989). The last C pulse of the HMQC experiment is in this case substituted by a selective 90° Gaussian pulse. Thus the soft pulse is used for coherence transfer and not for excitation at the beginning of the sequence, as is usual for other pulse sequences. The BIRD pulse and the A-i delay are optimized to suppress protons bound to nuclei As is adjusted to correspond to the direct H,C couplings. The soft pulse at the end of the pulse sequence (Fig. 7.8) serves to transfer the heteronuclear double-quantum coherence into the antiphase magnetization of the protons attached to the selectively excited C nuclei. 

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