Reduction with LAH

The least troublesome routes to 3,4-dihydro- and 1,2,3,4-tetrahydro-quinazoline are probably the reduction of quinazoline by sodium borohydride, in water for the former or in methanol for the latter. Both must be isolated as salts. The dihydroquinazoline may be formed also by reduction with LAH in ether (65JHC157). In contrast, 5,6,7,8-tetrahy-droquinazoline is best made by primary synthesis from 2-formylcyclohexanone and for-mamide (57CB942) or from cyclohexanone and trisformamidomethane (60CB1402). 

Si-H containing functional initiators have been obtained by reduction with LAH of the corresponding Si-Cl containing compounds. Conditions have been developed under which the benzylic chloride remains unchanged while the Si-Cl bond is converted to Si-H (for experimental details see Sect. H.C.). The initiators obtained are shown in Table 1. 

Reaction of 266a with suitable methyl alkyl amines having an asymmetric center at the neighboring carbon atom provided optically active amides 302, which after reduction with LAH gave optically active py razolylmethy-lamines 303 (92CB701). 

An improved procedure for the synthesis of a-allenic alcohols in good yields and with approximately 90% e.e. was reported by Olsson and Claesson (56). (- )-(S)-3-Butyne-2-ol (25) was converted into the monotetrahydropyranyl derivatives 26a to c, which gave on reduction with LAH in ether or THF the chiral allenes 27a to c (Scheme 4). The absolute configurations of 27b and c were... 

Seebach and Daum (75) investigated the properties of a chiral acyclic diol, 1,4-bis(dimethylamino)-(2S,35)- and (2K,3/ )-butane-2,3-diol (52) as a chiral auxiliary reagent for complexing with LAH. The diol is readily available from diethyl tartrate by conversion to the dimethylamide and reduction with LAH. The diol 52 could be converted to a 1 1 complex (53) with LAH (eq. [18]), which was used for the reduction of aldehydes and ketones in optical yields up to 75%. Since both enantiomers of 53 are available, dextro- or levorotatory products may be prepared. The chiral diol is readily recoverable without loss of optical activity. The (- )-52-LAH complex reduced dialkyl and aryl alkyl ketones to products enriched in the (S)-carbinol, whereas (+ )-52-LAH gives the opposite result. The highest optical yield of 75% was obtained in the reduction of 2,4,6-... 

Section III,B> ) The two methyl groups in 34 were formed from the corresponding methyl esters via reduction to the bis-hydroxymethyl compound followed by ditosylation and reduction with LAH. Both the intermediate diester and the derived dialcohol were separately cyclized to give the corresponding octahydrodibenzothiophenes (50% and 80%, respectively). However, no attempt to dehydrogenate these compounds to the dibenzothiophenes was made. This reaction obviously has considerable potential. 

The usual range of reactions has been recorded for the aldehydes of dibenzothiophene. Oxidation yields the corresponding acid, - reduction with LAH the corresponding alcohol, reduction under Huang-Minlon conditions the corresponding methyl compound, and two examples of the Cannizarro reaction have been described. ... 

Perhydropyrido[l,2-6]pyridazine was prepared from perhydropyrido [l,2-fc]pyridazin-2-one by reduction with LAH (65MI1, 65URP170506 66KGS91 78JA4012), and from 4,4a,5,6,7,8-hexahydro-3//-pyrido[l,2-b] pyridazine by catalytic reduction over Pt02 in acetic acid (68YZ216). Re-... 

Leontidine (152) when hydrogenated over PtOj in acetic acid gave tetrahydroleontidine (153), which formed leontidane (154) on reduction with LAH (Scheme 24). Oxidation of leontidine with potassium permanganate gave... 

The isomer of MIPT with a considerably less bunched up propyl group, N-methyl-N-propyltryptamine or MPT. This was made via the amide from indoleglyoxyl chloride and methylpropylamine, and reduction with LAH. MS (in m/z) C5H12N+ 86 (100%) indolemethylene+ 130 (8%) parent ion 216 (1%). Several human trials, up to twenty milligrams orally, showed no effects of any kind, so the activity, if there is any, is definitely less than that of MIPT. So the lumpiness of the isopropyl may be playing some role. There is no other way that is obvious of challenging this without adding more carbon atoms, and that would introduce another variable. This same decoration scheme has been used successfully in several other of the tryptamines in this story. 

The first synthesis of the borepin ring was performed in 1960 by van Tamelen and coworkers starting from 2,2 -dilithiobibenzyl according to Scheme 39 (60TL(8)14). The ethanolamine derivative (203) was isolated and characterized. Reduction with LAH gave a product, isolated as an unstable pyridine complex. The Lewis acid part of the complex was considered to have structure (204), but the conclusions were tentative, partly due to its re-oxidation to (20S). The corresponding synthetic strategy to non-fused borepins met with difficulties 4,5-dihydroborepin (206) could be prepared, but it was not possible to introduce the third double bond. 

EXTENSIONS AND COMMENTARY This is pretty sparse information upon which to build a picture of biological activity. First, the synthesis was done by someone else and, as I have not been able to find where the notes are, this will be the one recipe in the footnote without explicit directions incorporated. The procedure used was exactly the same as that described for DMMDA, except that the starting material was dillapiole rather than apiole. The dillapiole was obtained by the careful fractionation of Oil of Dill (as opposed to the isolation of apiole from the careful fractionation of Oil of Parsley). Isomerization to isodillapiole, nitration with tetra-nitromethane to give 1 -(2,3-dimethoxy-4,5-methylenedioxyphenyl)-2-nitropropene, and its reduction with LAH in ether to give 2,3-dimethoxy-4,5-methylenedioxyamphetamine hydrochloride (DMMDA-2) proceeded in a precisely analogous manner to the preparation of DMMDA. 

Primary and secondary alcohols can be converted to alkanes by conversion to tosylates followed by reduction with LAH. This reduction is valuable because deuterium can be easily introduced into the alkane by the use of lithium aluminum deuteride (LAD) instead of LAH. 

Oxazines (which can be readily formed from nitrosoalkenes and methoxyallene derivatives545) may be converted into aziridines by reduction with LAH. The reaction occurs in moderate yield, giving a preponderance of the cis product (equation 149)546. 

The formation of the y-lactams is almost perfectly diastereoselective if cyclic a-amino aldehydes or the aldehyde prepared from valine are used as starting materials. As it is shown in the following scheme, the electroreduction of the obtained optically pure y-lactams followed by the reduction with LAH yields the corresponding optically pure pyrrolizidine and indolizidine skeletons. 

The dienone (210) has also been prepared (152, 153) by oxidation of the amide (211) with potassium ferricyanide, when 212 was obtained in 67% yield. After protection of the phenolic hydroxyl group, reduction with LAH... 

Derivatives of pyridine-3,5-dicarboxylic acid have been shown to undergo reaction with lithium aluminum hydride by attack on the pyridine ring to form 1,4-dihydropyridines.57,58 Presumably the decrease in electron-density at the ring carbon atoms due to these substituents causes the ring to be extremely susceptible to hydride attack. Similar results were obtained with 3,5-dicyanopyridine derivatives. Methyl nicotinate, however, underwent reaction with LAH with exclusive reduction of the ester function.57 Recently the 3,5-dicyanopyridines have been reported to give mixtures of 1,2- and 1,4-dihydropyridines on reduction with LAH or sodium boro-hydride.20 ... 

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